Chronic rhinosinusitis: phenotypes and endotypes.

PURPOSE OF REVIEW: Chronic rhinosinusitis (CRS) is a broad classification of airway inflammation that affects a significant portion of the population. The current model of delineating patients suffering from CRS is dated and is no longer as simple as the presence of polyps or no polyps. Continued advances in the endotype descriptions of CRS have allowed for new phenotypic descriptions that aid in driving management and research efforts. RECENT FINDINGS: Geographic differences exist between patient presentations, which require a molecular evaluation of the driving forces. Increased understanding of these differences allows for patient-specific treatment decisions. SUMMARY: New descriptions of CRS phenotypes allow for more targeted therapy for patients, particularly to those with difficult to control disease. The previously broad classification of CRS with or without nasal polyps is no longer sufficient at driving these treatment decisions.

Allergy Testing - An Overview.

Childhood allergies pose huge economic burden and adverse effects on quality of life. Serum IgE has been considered a surrogate allergy marker for decades. Availability of several over-the-counter allergy tests add to confusion of partially trained caregivers. The present review focuses on current status of allergy testing in Indian scenario. Various in-vitro and in-vivo diagnostic modalities are available for allergy detection. Skin prick tests are useful for aero-allergies whereas oral challenge tests are best for identifying suspected food allergies. An allergy test should be individualized based on clinical features, diagnostic efficacy, and cost-benefit analysis.

Classification of hypersensitivity reactions.

As the primary defense against pathogens, the immune system uses numerous strategies to ensure optimal protection for the host. When immune responses go awry, however, they can cause great damage. "Hypersensitivity" is a broad term used to describe an excessive and/or pathogenic immune response to either foreign or self antigens. Gell and Coombs were the first to categorize hypersensitivity reactions into 4 types according to pathophysiology, but more recent insights into the mechanisms of these disorders have since modified the original classification system. This review describes the immune mechanisms involved in each of the modern Gell-Coombs categories.

A curated collection of transcriptome datasets to investigate the molecular mechanisms of immunoglobulin E-mediated atopic diseases.

Prevalence of allergies has reached ~20% of population in developed countries and sensitization rate to one or more allergens among school age children are approaching 50%. However, the combination of the complexity of atopic allergy susceptibility/development and environmental factors has made identification of gene biomarkers challenging. The amount of publicly accessible transcriptomic data presents an unprecedented opportunity for mechanistic discoveries and validation of complex disease signatures across studies. However, this necessitates structured methodologies and visual tools for the interpretation of results. Here, we present a curated collection of transcriptomic datasets relevant to immunoglobin E-mediated atopic diseases (ranging from allergies to primary immunodeficiencies). Thirty-three datasets from the Gene Expression Omnibus, encompassing 1860 transcriptome profiles, were made available on the Gene Expression Browser (GXB), an online and open-source web application that allows for the query, visualization and annotation of metadata. The thematic compositions, disease categories, sample number and platforms of the collection are described. Ranked gene lists and sample grouping are used to facilitate data visualization/interpretation and are available online via GXB (http://ige.gxbsidra.org/dm3/geneBrowser/list). Dataset validation using associated publications showed good concordance in GXB gene expression trend and fold-change.

Are outcome measures in allergic diseases relevant for the WHO's International Classification of Diseases in allergology?

PURPOSE OF REVIEW: To review and understand the impact of the outcome measures of allergic and hypersensitivity conditions for the WHO's International Classification of Diseases (ICD) and its impact in the management of anaphylaxis and identify potential strategies to improve patients' care and prevention. RECENT FINDINGS: The pioneer chapter addressed to allergic and hypersensitivity conditions in the 11th version of the WHO's ICD is the result of the evidence-based academic technical actions consistently following of collaborations of the allergy community and integrated international initiatives in order to reach quality outcomes measures of allergies worldwide. SUMMARY: Allergic and hypersensitivity conditions are increasing worldwide, however, they have never been well represented in the international classification systems, such as the ICD. The ALLERGY in ICD-11 initiative has been launched in 2012 in order to gather a better representation of these conditions in the ICD-11. As a result of the evidence-based academic technical actions acknowledged by the Joint Allergy Academies and the WHO, the pioneer chapter Allergy and hypersensitivity conditions has been constructed. This framework can be considered a milestone in the history of the allergy specialty. More reliable, accurate and comparable epidemiological data will be able to provide a big picture of these conditions and will support improvements in many levels of the health system. As knowledge derived from populations is key information for more realistic decision-making, the construction of the new section addressed to allergic and hypersensitivity conditions in the ICD-11 will allow the collection of more accurate epidemiological data to support quality management of patients, and better facilitate healthcare planning to implement public health measures to prevent and reduce the morbidity and mortality attributable to these conditions.

Scoring systems for allergies and asthma in clinical research and practice.

Background: Scoring systems are increasingly being developed for various diseases, including asthma and allergic disorders, with the objective of improving the classification of disease severity and the assessment of efficacy of therapeutic modalities. Objective: This review provided concise summaries of published scoring systems used for allergic rhinitis, asthma, atopic dermatitis, urticaria, Stevens-Johnson syndrome/toxic epidermal necrolysis, eosinophilic esophagitis, and systemic allergic reactions (anaphylaxis). Methods: We searched the medical literature between 1985 and 2018 for published scoring systems that have been developed and used in clinical trials or in practice for assessment of asthma and a variety of allergic disorders. Results: The scoring systems for each of these diseases were briefly presented in the text in chronological order of publication, and selected information was presented in the tables for easy comparisons. For more details, the reader should refer to the original relevant publications. Conclusion: Such assessment methods are useful for sound designing of clinical trials, fair comparisons of findings of studies, and objective measurements of patients' progress in clinical practice. The choice of using one scoring system over another would depend on its proven degree of validity, the purpose, and applicability.

[Oral allergies]. / Les allergies orales.

Oral allergies to dental materials are a growing problem and remain poorly diagnosed by health professionals. The complaints of patients with oral allergy are various and include sensations of burning or stinging of the oral mucosa, sensations of dryness of the oral cavity, or general symptoms such as headache, dyspepsia, asthenia, arthralgia, and myalgia. Signs suggestive of oral allergy include erythema, edema, purpuric patches on the palate, ulcerations of the oral mucosa (canker sore), gingivitis, glossitis mimicking geographic tongue, angular cheilitis, peri-oral eczema or the presence of lichenoid reactions of the oral mucosa. The diagnosis of an allergy will include data from the anamnesis, the clinical examination, as well as the results of allergy tests: epicutaneous tests (patch tests) or cutaneous tests (prick tests), possibly completed by a blood test ( in vitro lymphoblastic transformation test ou LTT).

Les allergies orales aux matériaux dentaires représentent un problème croissant et demeurent peu diagnostiquées par les professionnels de la santé. Les plaintes des patients présentant une allergie buccale sont variées et compor tent des sensations de brûlures ou de picotements de la muqueuse buccale, des sensations de sécheresse de la cavité buccale ou des symptômes généraux de type céphalée, dyspepsie, asthénie, arthralgies, myalgies. Les signes qui peuvent faire suspecter une allergie de la cavité buccale sont la présence d'un érythème, d'un oedème ou piqueté purpurique du palais, des ulcérations de la muqueuse buccale (aphtes), une gingivite, une glossite dépapillante, une perlèche, un eczéma péribuccal ou encore la présence de réactions lichénoïdes de la muqueuse buccale. Le diagnostic d'une allergie comprendra les données de l'anamnèse, de l'examen clinique, ainsi que les résultats des tests d'allergies : tests épicutanés (patch tests) ou cutanés (prick tests), complétés éventuellement par un test sanguin (test de transformation lymphoblastique in vitro ou LTT).

[Common questions about allergy. Practical approach to diagnosis and management in primary care]. / Preguntas comunes en alergias. Enfoque práctico para el diagnóstico y manejo en atención primaria.

Allergic diseases are disorders with different clinical manifestations that are present in 20 to 40% of the general population. Since they share a common mechanism, several processes of this type often occur in the same individual, thus generating numerous symptoms and important economic costs for patients and their families. Currently, medical management of these diseases is focused on three main aspects: to identify and avoid the causative agent, acute symptoms' control through pharmacological treatment and generation of tolerance with immunomodulation or desensitization. However, owing to the different underlying mechanisms, different diagnostic approaches are necessary, which can become a real challenge for the treating physician. In addition, sometimes patients undergo different restrictions and unnecessary treatments, thus limiting their daily activities, modifying their diet and directly affecting their quality of life. A review is made, aimed at answering different concerns arising from daily patient consultation.

Las alergias son enfermedades con diferentes manifestaciones clínicas, presentes en 20 a 40 % de la población general. Debido a que comparten un mismo mecanismo, en muchas ocasiones se presentan varios procesos de este tipo en una misma persona, generando numerosos síntomas y costos económicos importantes para el paciente y su familia. Actualmente, el manejo médico de estas enfermedades está enfocado en tres puntos principales: identificar y evitar el agente causal, control de los síntomas agudos mediante tratamiento farmacológico y generación de tolerancia con inmunomodulación o la desensibilización. Sin embargo, debido a los diferentes mecanismos subyacentes, es necesario realizar diferentes aproximaciones diagnósticas, las cuales pueden transformarse en un verdadero reto para el médico tratante. Adicionalmente, en ocasiones el paciente lleva a cabo restricciones y tratamientos innecesarios, limitando sus actividades diarias, modificando su dieta y afectando de forma directa su calidad de vida. Se realiza una revisión orientada a dar respuesta a diferentes inquietudes comunes que resultan de la consulta de la práctica diaria.

Allergen immunotherapy in people, dogs, cats and horses - differences, similarities and research needs.

In human patients with seasonal allergic rhinoconjunctivitis sensitized to grass pollen, the first successful allergen immunotherapy (AIT) was reported in 1911. Today, immunotherapy is an accepted treatment for allergic asthma, allergic rhinitis and hypersensitivities to insect venom. AIT is also used for atopic dermatitis and recently for food allergy. Subcutaneous, epicutaneous, intralymphatic, oral and sublingual protocols of AIT exist. In animals, most data are available in dogs where subcutaneous AIT is an accepted treatment for atopic dermatitis. Initiating a regulatory response and a production of "blocking" IgG antibodies with AIT are similar mechanisms in human beings and dogs with allergic diseases. Although subcutaneous immunotherapy is used for atopic dermatitis in cats, data for its efficacy are sparse. There is some evidence for successful treatment of feline asthma with AIT. In horses, most studies evaluate the effect of AIT on insect hypersensitivity with conflicting results although promising pilot studies have demonstrated the prophylaxis of insect hypersensitivity with recombinant antigens of biting midges (Culicoides spp.). Optimizing AIT using allergoids, peptide immunotherapy, recombinant allergens and new adjuvants with the different administration types of allergen extracts will further improve compliance and efficacy of this proven treatment modality.

Safety and Quality Recommendations in Allergy Medicine (Spanish acronym, RESCAL)

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Dermatitis alérgica de contacto pediátrica. Estudio clínico-epidemiológico en un hospital terciario / Pediatric Allergic Contact Dermatitis: Clinical and Epidemiological Study in a Tertiary Hospital

Introducción: Los estudios epidemiológicos sobre incidencia de dermatitis alérgica de contacto en población pediátrica son escasos. Algunos trabajos consideran que se trata de una entidad infradiagnosticada, y que en muchos casos no se sospecha clínicamente, no realizándose pruebas epicutáneas. No obstante se han comunicado tasas prevalencia de hasta el 20% de sensibilización a alérgenos en la población pediátrica, por lo que probablemente debería ser tenida en cuenta como una posibilidad diagnóstica en este grupo de edad. Material y método: Se ha realizado un análisis retrospectivo de la base de datos de alergia cutánea del servicio de Dermatología del Hospital General seleccionando los casos diagnosticados en niños de entre 0 y 16 años durante los últimos 15 años (año 2000 hasta 2015). El estudio incluye variables epidemiológicas (edad, sexo, antecedentes de atopia) y clínicas (localización de las lesiones, baterías de alérgenos empleadas, alérgenos positivos y su relevancia). Resultados: De los 4.593 pacientes estudiados con pruebas epicutáneas en los últimos 15 años, 265 (6%) correspondían a niños de 0-16 años. Ciento cuarenta y cuatro pacientes (54,3%) mostraron positividad para al menos uno de los alérgenos parcheados. Los alérgenos más frecuentemente identificados fueron en orden decreciente: tiomersal, cloruro de cobalto, colofonia, parafenilendiamina, dicromato potásico, mercurio y níquel. La sensibilización fue considerada de relevancia presente en 177 casos (61,3%). Conclusión: Más de la mitad de los niños estudiados mostraron sensibilización a uno o más alérgenos, con un porcentaje importante de sensibilizaciones relevantes. Todo niño con sospecha clínica de dermatitis alérgica de contacto debería ser remitido para realización de pruebas epicutáneas. Al no existir pruebas estandarizadas en este colectivo se requiere un alto nivel de sospecha clínica y un conocimiento de los alérgenos más frecuentemente implicados de cara a seleccionar los alérgenos a parchar (AU)

Background: Few epidemiological studies have investigated the incidence of allergic contact dermatitis in children. Underdiagnosis has been observed in some studies, with many cases in which the condition is not suspected clinically and patch tests are not performed. However, the prevalence of pediatric sensitization to allergens has been reported to be as high as 20%, and the diagnosis should therefore be contemplated as a possibility in this age group. Material and methods: We performed a retrospective analysis of the skin allergy database of the Dermatology Department of Consorcio Hospital General Universitario de Valencia. Children between 0 and 16 years of age diagnosed with allergic contact dermatitis in the previous 15 years (between 2000 and 2015) were included in the analysis. Epidemiological (age, sex, history of atopy) and clinical (site of the lesions, allergen series applied, positive reactions, and their relevance) variables were gathered. Results: Patch tests had been performed on 4,593 patients during the study period. Of these, 265 (6%) were children aged between 0 and 16 years. A positive reaction to at least one of the allergens tested was observed in 144 (54.3%) patients in that group. The allergens most frequently identified were the following (in decreasing order of frequency): thiomersal, cobalt chloride, colophony, paraphenylenediamine, potassium dichromate, mercury, and nickel. The sensitization was considered relevant in 177 (61.3%) cases. Conclusions: More than half of the children studied showed sensitization to 1 or more allergens, with a high percentage of relevant sensitizations. All children with a clinical suspicion of allergic contact dermatitis should be referred for patch testing. As no standardized test series have been developed for this age group, a high level of clinical suspicion and knowledge of the allergens most commonly involved are required when selecting the allergens to be tested (AU)

Classification of Tattoo Complications in a Hospital Material of 493 Adverse Events.

BACKGROUND/AIMS: Tattooing is a global trend. Clinical knowledge of complications is based on case reports collected over a century. Larger cohorts reflecting complications associated with contemporary trends are lacking. METHODS: The study was a retrospective review of a consecutive cohort of patients with tattoo complications diagnosed in the "Tattoo Clinic" of Bispebjerg University Hospital in Copenhagen, Denmark, from 2008 to 2015, based on patient history and systematic clinical examination. RESULTS: A total of 493 tattoo complications in 405 patients were studied. Overall, 184 (37%) presented allergic reactions with plaque elevation in 32.2%, excessive hyperkeratosis in 3.7%, and ulceration in 1.4%, predominantly observed in red tattoos and nuances of red; 66 (13%) presented papulo-nodular reactions, mainly observed in black tattoos (considered non-allergic) and due to pigment agglomeration; 53 (11%) had bacterial infections; 46 (9%) were psycho-social complications; 144 (30%) belonged to several specific diagnostic entities, including photosensitivity, pain syndrome, and lymphopathy. We found no cases of cutaneous or other malignancies. Sarcoidosis was primarily seen in black tattoos and was a common associated disease, found in 23 reactions (5%), compared to the background population. CONCLUSION: The study introduces a new concept of classification of tattoo complications based on simple tools such as patient history and objective findings supplemented with histology. The study reflects complications originating from presently used tattoo inks, often with organic pigments. The introduced classification has been submitted to the World Health Organisation (WHO) as a proposal to the 11th revision of the International Classification of Diseases.

Tiotropium improves lung function, exacerbation rate, and asthma control, independent of baseline characteristics including age, degree of airway obstruction, and allergic status.

BACKGROUND: Many patients with asthma remain symptomatic despite treatment with inhaled corticosteroids (ICS) with or without long-acting ß2-agonists (LABAs). Tiotropium add-on to ICS plus a LABA has been shown to improve lung function and reduce exacerbation risk in patients with symptomatic asthma. OBJECTIVE: To determine whether the efficacy of tiotropium add-on therapy is dependent on patients' baseline characteristics. METHODS: Two randomized, double-blind, parallel-group, twin trials (NCT00772538 and NCT00776984) of once-daily tiotropium Respimat(®) 5 µg add-on to ICS plus a LABA were performed in parallel in patients with severe symptomatic asthma. Exploratory subgroup analyses of peak forced expiratory volume in 1 s (FEV1), trough FEV1, time to first severe exacerbation, time to first episode of asthma worsening, and seven-question Asthma Control Questionnaire responder rate were performed to determine whether results were influenced by baseline characteristics. RESULTS: 912 patients were randomized: 456 received tiotropium and 456 received placebo. Tiotropium improved lung function, reduced the risk of asthma exacerbations and asthma worsening, and improved asthma symptom control, compared with placebo, independent of baseline characteristics including gender, age, body mass index, disease duration, age at asthma onset, and FEV1 % predicted at screening and reversibility. CONCLUSION: Once-daily tiotropium 5 µg compared with placebo improved lung function, reduced the risk of asthma exacerbations and asthma worsening, and improved asthma symptom control, independent of a broad range of baseline characteristics, as add-on to ICS plus LABAs in patients with severe symptomatic asthma. TRIAL REGISTRY: ClinicalTrials.gov; numbers NCT00772538 and NCT00776984 URL: www.clinicaltrials.gov.

Progestogen Hypersensitivity in 24 Cases: Diagnosis, Management, and Proposed Renaming and Classification.

BACKGROUND: Autoimmune progesterone dermatitis is a poorly recognized syndrome associated with a hypersensitivity to progestogens. Symptoms present heterogeneously, which may complicate diagnosis. Management has generally centered on symptomatic control with medication. Recently, an increasing number of cases have been reported with in vitro fertilization (IVF). Desensitization to progestogens is suggested as an approach to tolerate fertility treatments and provide symptom control. OBJECTIVES: To describe the diagnosis and management of progestogen hypersensitivity (PH) and to detail the use of desensitization. We also propose a new terminology of progestogen hypersensitivity instead of autoimmune progesterone dermatitis, and a classification system based on exogenous and endogenous progestogen triggers to facilitate diagnosis and management. METHODS: Twenty-four cases of PH were evaluated retrospectively. Symptom presentation, diagnostic modalities, desensitization protocols, and outcomes were analyzed. RESULTS: Symptom onset was classified as a reaction to either endogenous progesterone (42%) or exogenous progestogens (58%). Symptoms were heterogeneous and included cyclical dermatitis, urticaria, angioedema, asthma, and anaphylaxis. Triggers were also heterogenous and included progesterone as well as progestins. Eleven patients underwent intramuscular (27%) or oral (73%) desensitization. Desensitization resulted in symptom control in 8 patients, IVF medication tolerance in 3 patients, and 2 pregnancies. CONCLUSIONS: This is the largest case series of patients with PH with successful treatment outcomes. The new terminology progestogen hypersensitivity more accurately represents the diversity of presentations to endogenous or exogenous progestogens. We demonstrate that progestogen desensitization is successful in multiple patients and can result in symptom control and fertility. Women with cyclical allergic symptoms, including those undergoing IVF, should be evaluated for PH.

Systematic Review on the Definition of Allergic Diseases in Children: The MeDALL Study.

BACKGROUND: During the last decades, a large number of phenotypes and disease classifications of allergic diseases have been proposed. Despite the heterogeneity across studies, no systematic review has been conducted on phenotype classification and the criteria that define allergic diseases. We aimed to identify clinically expressed, population-based phenotypes of allergic diseases and their interrelationships, to explore disease heterogeneity and to evaluate the measurements employed in disease diagnosis. METHODS: We conducted a search of MEDLINE up to December 2012, to identify relevant original studies published in the English language that examine at least one objective of this systematic review in subjects aged 0-18 years. The screening of titles and abstracts and the extraction of data were conducted independently by two reviewers. RESULTS: From a total of 13,767 citations, 197 studies met the criteria for inclusion, with 54% being cohort studies. Allergic diseases were studied as a single entity in 55% (109/197) of the studies or in the context of multimorbidity in 45%. Asthma accounted for 81.7% of the studies examining single diseases. Overall, up to 33 different phenotypes of allergic disease were reported. Transient early, late-onset and persistent wheeze were the most frequently reported phenotypes. Most studies (78%) used questionnaires. The skin-prick test was the preferred measurement of sensitization (64%). Spirometry and bronchial hyperresponsiveness were assessed in one third of the studies, peak flow rate in 8.6% and disease severity in 35%. CONCLUSIONS: Studies reporting phenotypes of allergic diseases in children are highly heterogeneous and often lack objective phenotypical measures. A concerted effort to standardize methods and terminology is necessary.

Perioperative anaphylactic reactions: Review and procedure protocol in paediatrics

Perioperative anaphylactic reactions are immediate, hypersensitive reactions that are potentially life-threatening resulting from a sudden release of mediators from mast cells and basophiles, due to either immune (IgE or non-IgE mediated) or non-immune mechanisms. The most frequent causing agents are neuromuscular blocking agents (NMBAs), latex and antibiotics, with latex being the first cause in paediatrics. With regard to perioperative anaphylactic reactions, the usual early signs and symptoms of an anaphylactic reaction could be overlooked or erroneously interpreted and non-severe anaphylaxis could go undetected, with a risk of more severe reactions in the future. Using the data registered on the anaesthesia sheet, it is essential to establish a chronological relationship between drugs and/or substances administered and the reaction observed. An elevated level of tryptase confirms an anaphylactic reaction, but this does not usually increase in the absence of compromised circulation. An allergy study should be carried out preferably between 4 and 6 weeks after the reaction, using a combination of specific IgE, skin and controlled exposure tests (if indicated). Test sensitivity is good for NMBAs, latex, antibiotics, chlorhexidine, gelatine and povidone, and poor for barbiturates, opiates (these can give false positives since they are histamine releasers) and benzodiazepines. Special preventive measures should be taken, especially in the case of latex. We present the maximum concentrations recommended for skin tests, the recommended dosage to treat anaphylactic reactions in paediatrics and a procedure algorithm for the allergological study of these reactions

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