- The document summarizes recent articles from Allergy and Annals of Allergy, Asthma & Immunology journals. It discusses topics such as exercise-induced bronchoconstriction in athletes, effectiveness of low-dose aspirin for treating aspirin-exacerbated respiratory disease, and diversity of allergens in dog saliva. The author is Juan Carlos Aldave Becerra, an allergy/immunology physician providing this educational summary for other physicians. Any feedback or questions should be directed to the author by email.
This document provides a summary of recent literature on allergic diseases from the journal Allergy in January 2013. It includes the following key points:
- A study found that uncontrolled asthma and nasal congestion are independent risk factors for insomnia.
- Studies showed that sublingual grass tablet immunotherapy had similar efficacy and safety in both mono- and polysensitized individuals with grass pollen allergy.
- A study found that higher maternal vitamin D levels during pregnancy were associated with increased risk of food allergy in children in the first 2 years of life.
- Mechanisms of peripheral tolerance to allergens were summarized, including the roles of regulatory T cells, dendritic cells, cytokines, and cell surface
Pearls in Allergy and Immunology 2013 SeptemberJuan Aldave
This document provides a summary of recent literature on allergy and immunology. It discusses several topics:
- Thermal processing can reduce the allergenicity of some tree nuts but not others. Skin testing is useful for diagnosing proton pump inhibitor allergies.
- Atopic eczema is caused by skin barrier defects, innate immune dysregulation that promotes TH2 inflammation, and adaptive immune dysregulation from genetic and environmental factors.
- The document is intended for educational purposes for allergy/immunology physicians and does not replace their clinical judgement. Suggestions to improve the content should be sent to the author.
Alpha-Gal Syndrome, also known as red meat allergy, is caused by IgE antibodies against the carbohydrate galactose-alpha-1,3-galactose (α-Gal) found in most mammals except primates. Tick bites transmit α-Gal to humans, causing an immune response. Reactions to red meat occur 2-6 hours after consumption due to the delayed absorption of α-Gal from glycoproteins and glycolipids. Management involves avoiding red meat, organs, and secondary exposures. The syndrome is increasingly recognized globally where ticks that transmit α-Gal are present.
2013 june Pearls in Allergy and Clinical ImmunologyJuan Aldave
This document provides a summary of recent literature on allergy and immunology. It discusses several topics, including adherence to immunotherapy during financial crises, allergic reactions after immunization, and diagnosing gelatin allergy following vaccine reactions. The purpose is exclusively educational to provide updated knowledge for physicians, and does not replace clinical judgment. Suggestions to improve the content are welcome.
The document discusses alpha-gal syndrome, which causes delayed allergic reactions to red meat in some individuals. It may be triggered by tick bites that induce IgE antibodies against the alpha-gal oligosaccharide found in mammalian meat. Patients report generalized hives, swelling, or anaphylaxis hours after eating beef, pork or lamb. The condition is diagnosed by positive tests for alpha-gal IgE antibodies. Management involves strictly avoiding all mammalian meat and organs as well as tick bites. The cause of the delayed reactions and high antibody levels from tick bites remains unknown.
This document discusses wheat allergy and related topics. It begins by classifying wheat taxonomically and describing its major protein components, many of which are allergens. It then discusses the epidemiology and clinical manifestations of wheat allergy, including immediate IgE-mediated reactions, allergic contact urticaria, baker's asthma, food-dependent exercise-induced anaphylaxis, associations with atopic dermatitis, and eosinophilic gastrointestinal disorders. Mechanisms of allergenic cross-reactivity between wheat and other cereals as well as grasses are also reviewed.
This document discusses the immunologic mechanisms of anaphylaxis. It describes IgE-dependent and IgG-mediated pathways that can trigger anaphylaxis through cross-linking of antibodies on mast cells and basophils. It also discusses non-immunologic triggers like direct mast cell activation and complement activation. A variety of mediators are released that can cause signs and symptoms. The classification of reactions and potential effector cells involved are presented.
Pearls in Allergy and Immunology October 2013Juan Aldave
This article discusses cofactors that can lower the threshold for anaphylaxis in sensitized individuals. Common cofactors include physical exercise, alcohol, infections, NSAIDs, and certain drugs. Mechanisms by which cofactors can induce anaphylaxis include increasing allergen absorption, lowering the activation threshold of mast cells and basophils, increasing leukotriene synthesis, and stimulating the immune system during infections. Understanding cofactors is important for managing anaphylaxis risk.
This document provides a summary of recent literature on allergic diseases from the journal Allergy in January 2013. It includes the following key points:
- A study found that uncontrolled asthma and nasal congestion are independent risk factors for insomnia.
- Studies showed that sublingual grass tablet immunotherapy had similar efficacy and safety in both mono- and polysensitized individuals with grass pollen allergy.
- A study found that higher maternal vitamin D levels during pregnancy were associated with increased risk of food allergy in children in the first 2 years of life.
- Mechanisms of peripheral tolerance to allergens were summarized, including the roles of regulatory T cells, dendritic cells, cytokines, and cell surface
Pearls in Allergy and Immunology 2013 SeptemberJuan Aldave
This document provides a summary of recent literature on allergy and immunology. It discusses several topics:
- Thermal processing can reduce the allergenicity of some tree nuts but not others. Skin testing is useful for diagnosing proton pump inhibitor allergies.
- Atopic eczema is caused by skin barrier defects, innate immune dysregulation that promotes TH2 inflammation, and adaptive immune dysregulation from genetic and environmental factors.
- The document is intended for educational purposes for allergy/immunology physicians and does not replace their clinical judgement. Suggestions to improve the content should be sent to the author.
Alpha-Gal Syndrome, also known as red meat allergy, is caused by IgE antibodies against the carbohydrate galactose-alpha-1,3-galactose (α-Gal) found in most mammals except primates. Tick bites transmit α-Gal to humans, causing an immune response. Reactions to red meat occur 2-6 hours after consumption due to the delayed absorption of α-Gal from glycoproteins and glycolipids. Management involves avoiding red meat, organs, and secondary exposures. The syndrome is increasingly recognized globally where ticks that transmit α-Gal are present.
2013 june Pearls in Allergy and Clinical ImmunologyJuan Aldave
This document provides a summary of recent literature on allergy and immunology. It discusses several topics, including adherence to immunotherapy during financial crises, allergic reactions after immunization, and diagnosing gelatin allergy following vaccine reactions. The purpose is exclusively educational to provide updated knowledge for physicians, and does not replace clinical judgment. Suggestions to improve the content are welcome.
The document discusses alpha-gal syndrome, which causes delayed allergic reactions to red meat in some individuals. It may be triggered by tick bites that induce IgE antibodies against the alpha-gal oligosaccharide found in mammalian meat. Patients report generalized hives, swelling, or anaphylaxis hours after eating beef, pork or lamb. The condition is diagnosed by positive tests for alpha-gal IgE antibodies. Management involves strictly avoiding all mammalian meat and organs as well as tick bites. The cause of the delayed reactions and high antibody levels from tick bites remains unknown.
This document discusses wheat allergy and related topics. It begins by classifying wheat taxonomically and describing its major protein components, many of which are allergens. It then discusses the epidemiology and clinical manifestations of wheat allergy, including immediate IgE-mediated reactions, allergic contact urticaria, baker's asthma, food-dependent exercise-induced anaphylaxis, associations with atopic dermatitis, and eosinophilic gastrointestinal disorders. Mechanisms of allergenic cross-reactivity between wheat and other cereals as well as grasses are also reviewed.
This document discusses the immunologic mechanisms of anaphylaxis. It describes IgE-dependent and IgG-mediated pathways that can trigger anaphylaxis through cross-linking of antibodies on mast cells and basophils. It also discusses non-immunologic triggers like direct mast cell activation and complement activation. A variety of mediators are released that can cause signs and symptoms. The classification of reactions and potential effector cells involved are presented.
Pearls in Allergy and Immunology October 2013Juan Aldave
This article discusses cofactors that can lower the threshold for anaphylaxis in sensitized individuals. Common cofactors include physical exercise, alcohol, infections, NSAIDs, and certain drugs. Mechanisms by which cofactors can induce anaphylaxis include increasing allergen absorption, lowering the activation threshold of mast cells and basophils, increasing leukotriene synthesis, and stimulating the immune system during infections. Understanding cofactors is important for managing anaphylaxis risk.
This document provides a summary of recent publications in allergy and immunology. It discusses the results of studies on the effects of acupuncture for allergic rhinitis, the lack of correlation between blood and airway eosinophil counts in children with severe asthma, and new insights into eosinophil-derived cytokines and their selective secretion. The purpose is to provide updated practical knowledge for allergy/immunology physicians.
Red meat allergy, also known as alpha-gal allergy, is caused by IgE antibodies to the carbohydrate epitope galactose-alpha-1,3-galactose (alpha-gal) found in mammalian meats. Certain tick bites, such as from the lone star tick, are associated with the production of these IgE antibodies. Reactions to red meat following tick bites are often delayed 3-6 hours after ingestion. The discovery of the alpha-gal allergy has provided insights into regional differences in food allergies and advanced understanding of how environmental exposures can induce novel food allergies.
Pearls in Allergy and Immunology - May 2014Juan Aldave
This document provides an overview of recent literature on drug allergies and hypersensitivity reactions. It discusses the definition and classification of drug hypersensitivity reactions based on symptoms, timing and pathogenic mechanisms. Drug hypersensitivity reactions can be either immune-mediated (allergic) involving specific antibodies or T cells against the drug, or non-immune mediated involving non-allergic mechanisms like nonspecific mast cell activation. The document also discusses pathogenic mechanisms for different types of drug allergies classified from type I to type IV, as well as mechanisms of immune activation against drugs like the hapten concept.
The document summarizes wheat allergy, including its prevalence, major wheat proteins and allergens, cross-reactivity with other grains, and clinical manifestations. Some key points:
- Wheat allergy prevalence varies from 0.4-1% depending on age and region, and is particularly common in Japanese and Thai children.
- Major wheat allergens include omega-5-gliadin, lipid transfer proteins, glutenins, and alpha-purothionin.
- There is extensive cross-reactivity between wheat and other grains like rye and barley due to similar protein structures.
- Clinical manifestations include atopic dermatitis, anaphylaxis, baker's asthma
2013 August - Pearls in Allergy and ImmunologyJuan Aldave
This summary discusses two articles from the Annals of Allergy, Asthma & Immunology. The first article reports a case of relapsing polychondritis, an immune-mediated cartilage inflammation, in a patient who also had hypogammaglobulinemia of unknown origin. The patient's polychondritis significantly improved with corticosteroids and methotrexate. The second article reviews advances in the diagnosis and management of insect sting allergy, noting epidemiology, risk stratification of patients, diagnostic tests and their limitations, and novel diagnostic approaches such as basophil activation testing.
Pearls in Allergy and Immunology - June 2014Juan Aldave
The document provides an overview of recent literature on allergic diseases and immunology from the journal Allergy in June 2014. It summarizes several articles, including on the classification, diagnosis and treatment of angioedema, guidelines on the primary prevention of food allergy, a global survey on the classification and coding of hypersensitivity diseases, and gaps in evidence around factors that may influence the development of food allergies. The purpose is to provide updated practical knowledge for physicians in allergy and immunology.
Pears in Allergy and Immunology, April 2014Juan Aldave
The document provides an educational summary of recent articles in allergy and immunology from April 2014. It includes summaries of articles on:
1) A position paper on work-related chronic cough that describes its causes, diagnosis, and management depending on etiology. Common causes include work-related asthma, rhinosinusitis, and COPD.
2) A review on the roles of histamine in the gut, including its pro-inflammatory and anti-inflammatory effects depending on receptor activation, and metabolism by diamine oxidase and histamine-N-methyltransferase.
3) A potential novel mechanism of allergen-specific desensitization involving IgG-mediated down-regulation of IgE bound to mast cells
Pearls in Allergy and Immunology - August 2014Juan Aldave
The document summarizes recent guidelines on anaphylaxis from the European Academy of Allergy and Clinical Immunology. It discusses:
1) The definition, prevalence, mechanisms, common triggers, factors influencing severity, diagnosis and treatment of anaphylaxis.
2) The mechanisms of action of epinephrine and its role as first-line treatment.
3) Common cofactors ("augmentation factors") that can lower the threshold for anaphylaxis, including physical exercise, alcohol, infections, NSAIDs and certain drugs.
The document provides an educational summary of recent literature on allergy and immunology for physicians. It includes brief summaries of multiple journal articles on topics like drug allergy diagnosis, anaphylaxis, asthma, food allergy, primary immunodeficiencies, and more. The purpose is stated as being exclusively educational to provide practical knowledge for physicians, while not replacing clinical judgment. Contact information is provided for the author in case of questions.
This document provides an overview of shellfish allergy, including:
- Classification of different types of shellfish such as crustaceans, mollusks, and others.
- Epidemiology showing shellfish allergy prevalence is around 2% and is a common cause of anaphylaxis.
- Major allergens in shellfish like tropomyosin and their heat stability and cross-reactivity.
- Clinical manifestations ranging from mild oral symptoms to anaphylaxis and factors affecting reactions.
- Diagnosis involving patient history, skin prick tests, food challenges and IgE antibody tests to confirm allergy.
This document summarizes information about fish allergy. It discusses the epidemiology of fish allergy, classification of different types of fish, major fish allergens like parvalbumin and tropomyosin, diagnosis of fish allergy using methods like skin prick tests and IgE testing, cross-reactivity between fish species, and non-allergic adverse reactions to fish like scombroid poisoning and marine algae toxins. The classification section describes the different phylogenetic groups of fish including cartilaginous fish, ray-finned fish, and lobe-finned fish.
Pearls in Allergy and Immunology, December 2013Juan Aldave
The purpose of this summary is exclusively educational, to provide practical updated knowledge for Allergy/Immunology Physicians. It does not intend to replace the clinical criteria of the physician.
- A study of 204 patients with delayed hypersensitivity to penicillins found that all patients tolerated drug challenges with carbapenems, suggesting an absence of cross-reactivity. Skin tests and graded challenges are still advised for patients needing carbapenems who experienced severe penicillin reactions.
- Anaphylaxis is an acute severe allergic reaction potentially fatal. Most common triggers are foods, drugs, insects. Factors influencing severity include pathogenic mechanism, allergen properties, dose, route of exposure, sensitization level.
Omalizumab is a monoclonal antibody that binds to immunoglobulin E (IgE), reducing free IgE levels. It is used to treat allergic asthma and rhinitis. Clinical trials show omalizumab significantly reduces asthma exacerbations and improves symptoms and quality of life in patients with moderate-to-severe allergic asthma. It also reduces airway inflammation and thickness. Omalizumab allows reduction of inhaled corticosteroid use without worsening asthma control. Real-world studies find omalizumab effectively improves asthma control long-term with an acceptable safety profile.
Pearls in Allergy and Immunology - July 2014Juan Aldave
The purpose of the document is to provide educational material for Allergy/Immunology physicians. It summarizes several recent journal articles on topics related to allergy and immunology. Specifically, it discusses that allergic rhinitis is a risk factor for decreased traffic safety due to impaired cognitive and psychomotor functions. It also summarizes articles on differences in IgE sensitization patterns between atopic dermatitis and other hyper-IgE syndromes. Additionally, it discusses the efficacy of IgE-targeted versus empirical elimination diets for eosinophilic esophagitis.
Pearls in Allergy and Immunology, March 2014Juan Aldave
The document summarizes a systematic review on the acute and long-term management of food allergy. Key points include:
- Food allergy can be IgE-mediated, non-IgE mediated, or both IgE- and cell-mediated. The most common allergenic foods are milk, egg, peanut, tree nuts, wheat, soy, and seafood.
- Diagnosis involves skin prick tests, in vitro IgE tests, and food challenges. Treatment focuses on avoidance, epinephrine autoinjectors, and monitoring for tolerance development.
- The review found weak evidence that antihistamines may help non-life threatening reactions and mast cell stabilizers may reduce symptoms. Extensively hydro
The document discusses vaccine hypersensitivity and provides the following information:
1. It outlines the evolution of immunization programs from the pre-vaccine era to modern times and discusses the relationship between vaccine usage and adverse events.
2. It reviews the epidemiology of immediate hypersensitivity reactions to vaccines in the US and Australia, finding reporting rates of 10 per 100,000 doses in the US and incidence of potential IgE-mediated reactions of 5.4 per 100,000 doses in Australia.
3. It examines allergic reactions to specific vaccine constituents like gelatin and egg, noting the need to consider alternative vaccines or precautions in individuals with a history of allergy to these ingredients.
- Nut allergy is commonly caused by peanuts and tree nuts and can cause anaphylaxis. Peanut allergy prevalence is 0.5-2.5% in children in the UK and tree nut allergy prevalence is 0.2-2.2%.
- Diagnosis involves taking a history, skin prick tests, nut-specific IgE levels, and oral food challenges. Skin prick tests ≥3mm or nut-specific IgE levels ≥15kU/L suggest allergy.
- Cross-reactivity between peanuts and tree nuts is common, so testing for multiple nuts is often recommended for those allergic to one type of nut. Component resolved testing for Ara h 2
Eosinophilic gastrointestinal disorders (EGIDs) are characterized by eosinophil-rich inflammation in the GI tract without an identified cause. They include eosinophilic esophagitis (EoE), eosinophilic gastritis, eosinophilic gastroenteritis (EGE), and eosinophilic colitis (EC). Eosinophils accumulate in the GI tract due to cytokines like IL-3, IL-5, and eotaxin that enhance eosinophil development, migration, and function. Eosinophil granule proteins are toxic and cause tissue damage. Diagnosis requires endoscopy with biopsy showing ≥15 eos/hpf in the esophagus or ≥30 eos
2013 July - Pearls in Allergy and ImmunologyJuan Aldave
The document provides a summary of recent literature on allergy and immunology. It discusses several topics:
1) A consensus report that recommends the term "allergen immunotherapy" to describe therapy of allergic diseases with allergen-containing products.
2) Research on eosinophils and their role in allergic inflammation, including potential new treatment targets.
3) A position paper on desensitization for patients with delayed drug hypersensitivity reactions.
4) A study finding frequent sensitization to Candida albicans and profilins in adult eosinophilic esophagitis patients.
The purpose is to provide updated practical knowledge for physicians, though it does not replace clinical judgment
Pearls in Allergy and Immunology - February 2014 Juan Aldave
The document summarizes recent literature on allergic diseases from the journal Allergy and Annals of Allergy, Asthma and Immunology. It discusses topics such as atopic dermatitis, the atopic march, food allergy epidemiology and diagnosis, asthma phenotypes, new therapies for atopic dermatitis and allergic asthma, and the role of filaggrin mutations and phospholipids in omalizumab treatment efficacy for atopic dermatitis. The purpose is to provide updated knowledge for allergy/immunology physicians, though it does not replace clinical judgment. Any corrections or suggestions should be sent directly to the author.
This document provides a summary of recent publications in allergy and immunology. It discusses the results of studies on the effects of acupuncture for allergic rhinitis, the lack of correlation between blood and airway eosinophil counts in children with severe asthma, and new insights into eosinophil-derived cytokines and their selective secretion. The purpose is to provide updated practical knowledge for allergy/immunology physicians.
Red meat allergy, also known as alpha-gal allergy, is caused by IgE antibodies to the carbohydrate epitope galactose-alpha-1,3-galactose (alpha-gal) found in mammalian meats. Certain tick bites, such as from the lone star tick, are associated with the production of these IgE antibodies. Reactions to red meat following tick bites are often delayed 3-6 hours after ingestion. The discovery of the alpha-gal allergy has provided insights into regional differences in food allergies and advanced understanding of how environmental exposures can induce novel food allergies.
Pearls in Allergy and Immunology - May 2014Juan Aldave
This document provides an overview of recent literature on drug allergies and hypersensitivity reactions. It discusses the definition and classification of drug hypersensitivity reactions based on symptoms, timing and pathogenic mechanisms. Drug hypersensitivity reactions can be either immune-mediated (allergic) involving specific antibodies or T cells against the drug, or non-immune mediated involving non-allergic mechanisms like nonspecific mast cell activation. The document also discusses pathogenic mechanisms for different types of drug allergies classified from type I to type IV, as well as mechanisms of immune activation against drugs like the hapten concept.
The document summarizes wheat allergy, including its prevalence, major wheat proteins and allergens, cross-reactivity with other grains, and clinical manifestations. Some key points:
- Wheat allergy prevalence varies from 0.4-1% depending on age and region, and is particularly common in Japanese and Thai children.
- Major wheat allergens include omega-5-gliadin, lipid transfer proteins, glutenins, and alpha-purothionin.
- There is extensive cross-reactivity between wheat and other grains like rye and barley due to similar protein structures.
- Clinical manifestations include atopic dermatitis, anaphylaxis, baker's asthma
2013 August - Pearls in Allergy and ImmunologyJuan Aldave
This summary discusses two articles from the Annals of Allergy, Asthma & Immunology. The first article reports a case of relapsing polychondritis, an immune-mediated cartilage inflammation, in a patient who also had hypogammaglobulinemia of unknown origin. The patient's polychondritis significantly improved with corticosteroids and methotrexate. The second article reviews advances in the diagnosis and management of insect sting allergy, noting epidemiology, risk stratification of patients, diagnostic tests and their limitations, and novel diagnostic approaches such as basophil activation testing.
Pearls in Allergy and Immunology - June 2014Juan Aldave
The document provides an overview of recent literature on allergic diseases and immunology from the journal Allergy in June 2014. It summarizes several articles, including on the classification, diagnosis and treatment of angioedema, guidelines on the primary prevention of food allergy, a global survey on the classification and coding of hypersensitivity diseases, and gaps in evidence around factors that may influence the development of food allergies. The purpose is to provide updated practical knowledge for physicians in allergy and immunology.
Pears in Allergy and Immunology, April 2014Juan Aldave
The document provides an educational summary of recent articles in allergy and immunology from April 2014. It includes summaries of articles on:
1) A position paper on work-related chronic cough that describes its causes, diagnosis, and management depending on etiology. Common causes include work-related asthma, rhinosinusitis, and COPD.
2) A review on the roles of histamine in the gut, including its pro-inflammatory and anti-inflammatory effects depending on receptor activation, and metabolism by diamine oxidase and histamine-N-methyltransferase.
3) A potential novel mechanism of allergen-specific desensitization involving IgG-mediated down-regulation of IgE bound to mast cells
Pearls in Allergy and Immunology - August 2014Juan Aldave
The document summarizes recent guidelines on anaphylaxis from the European Academy of Allergy and Clinical Immunology. It discusses:
1) The definition, prevalence, mechanisms, common triggers, factors influencing severity, diagnosis and treatment of anaphylaxis.
2) The mechanisms of action of epinephrine and its role as first-line treatment.
3) Common cofactors ("augmentation factors") that can lower the threshold for anaphylaxis, including physical exercise, alcohol, infections, NSAIDs and certain drugs.
The document provides an educational summary of recent literature on allergy and immunology for physicians. It includes brief summaries of multiple journal articles on topics like drug allergy diagnosis, anaphylaxis, asthma, food allergy, primary immunodeficiencies, and more. The purpose is stated as being exclusively educational to provide practical knowledge for physicians, while not replacing clinical judgment. Contact information is provided for the author in case of questions.
This document provides an overview of shellfish allergy, including:
- Classification of different types of shellfish such as crustaceans, mollusks, and others.
- Epidemiology showing shellfish allergy prevalence is around 2% and is a common cause of anaphylaxis.
- Major allergens in shellfish like tropomyosin and their heat stability and cross-reactivity.
- Clinical manifestations ranging from mild oral symptoms to anaphylaxis and factors affecting reactions.
- Diagnosis involving patient history, skin prick tests, food challenges and IgE antibody tests to confirm allergy.
This document summarizes information about fish allergy. It discusses the epidemiology of fish allergy, classification of different types of fish, major fish allergens like parvalbumin and tropomyosin, diagnosis of fish allergy using methods like skin prick tests and IgE testing, cross-reactivity between fish species, and non-allergic adverse reactions to fish like scombroid poisoning and marine algae toxins. The classification section describes the different phylogenetic groups of fish including cartilaginous fish, ray-finned fish, and lobe-finned fish.
Pearls in Allergy and Immunology, December 2013Juan Aldave
The purpose of this summary is exclusively educational, to provide practical updated knowledge for Allergy/Immunology Physicians. It does not intend to replace the clinical criteria of the physician.
- A study of 204 patients with delayed hypersensitivity to penicillins found that all patients tolerated drug challenges with carbapenems, suggesting an absence of cross-reactivity. Skin tests and graded challenges are still advised for patients needing carbapenems who experienced severe penicillin reactions.
- Anaphylaxis is an acute severe allergic reaction potentially fatal. Most common triggers are foods, drugs, insects. Factors influencing severity include pathogenic mechanism, allergen properties, dose, route of exposure, sensitization level.
Omalizumab is a monoclonal antibody that binds to immunoglobulin E (IgE), reducing free IgE levels. It is used to treat allergic asthma and rhinitis. Clinical trials show omalizumab significantly reduces asthma exacerbations and improves symptoms and quality of life in patients with moderate-to-severe allergic asthma. It also reduces airway inflammation and thickness. Omalizumab allows reduction of inhaled corticosteroid use without worsening asthma control. Real-world studies find omalizumab effectively improves asthma control long-term with an acceptable safety profile.
Pearls in Allergy and Immunology - July 2014Juan Aldave
The purpose of the document is to provide educational material for Allergy/Immunology physicians. It summarizes several recent journal articles on topics related to allergy and immunology. Specifically, it discusses that allergic rhinitis is a risk factor for decreased traffic safety due to impaired cognitive and psychomotor functions. It also summarizes articles on differences in IgE sensitization patterns between atopic dermatitis and other hyper-IgE syndromes. Additionally, it discusses the efficacy of IgE-targeted versus empirical elimination diets for eosinophilic esophagitis.
Pearls in Allergy and Immunology, March 2014Juan Aldave
The document summarizes a systematic review on the acute and long-term management of food allergy. Key points include:
- Food allergy can be IgE-mediated, non-IgE mediated, or both IgE- and cell-mediated. The most common allergenic foods are milk, egg, peanut, tree nuts, wheat, soy, and seafood.
- Diagnosis involves skin prick tests, in vitro IgE tests, and food challenges. Treatment focuses on avoidance, epinephrine autoinjectors, and monitoring for tolerance development.
- The review found weak evidence that antihistamines may help non-life threatening reactions and mast cell stabilizers may reduce symptoms. Extensively hydro
The document discusses vaccine hypersensitivity and provides the following information:
1. It outlines the evolution of immunization programs from the pre-vaccine era to modern times and discusses the relationship between vaccine usage and adverse events.
2. It reviews the epidemiology of immediate hypersensitivity reactions to vaccines in the US and Australia, finding reporting rates of 10 per 100,000 doses in the US and incidence of potential IgE-mediated reactions of 5.4 per 100,000 doses in Australia.
3. It examines allergic reactions to specific vaccine constituents like gelatin and egg, noting the need to consider alternative vaccines or precautions in individuals with a history of allergy to these ingredients.
- Nut allergy is commonly caused by peanuts and tree nuts and can cause anaphylaxis. Peanut allergy prevalence is 0.5-2.5% in children in the UK and tree nut allergy prevalence is 0.2-2.2%.
- Diagnosis involves taking a history, skin prick tests, nut-specific IgE levels, and oral food challenges. Skin prick tests ≥3mm or nut-specific IgE levels ≥15kU/L suggest allergy.
- Cross-reactivity between peanuts and tree nuts is common, so testing for multiple nuts is often recommended for those allergic to one type of nut. Component resolved testing for Ara h 2
Eosinophilic gastrointestinal disorders (EGIDs) are characterized by eosinophil-rich inflammation in the GI tract without an identified cause. They include eosinophilic esophagitis (EoE), eosinophilic gastritis, eosinophilic gastroenteritis (EGE), and eosinophilic colitis (EC). Eosinophils accumulate in the GI tract due to cytokines like IL-3, IL-5, and eotaxin that enhance eosinophil development, migration, and function. Eosinophil granule proteins are toxic and cause tissue damage. Diagnosis requires endoscopy with biopsy showing ≥15 eos/hpf in the esophagus or ≥30 eos
2013 July - Pearls in Allergy and ImmunologyJuan Aldave
The document provides a summary of recent literature on allergy and immunology. It discusses several topics:
1) A consensus report that recommends the term "allergen immunotherapy" to describe therapy of allergic diseases with allergen-containing products.
2) Research on eosinophils and their role in allergic inflammation, including potential new treatment targets.
3) A position paper on desensitization for patients with delayed drug hypersensitivity reactions.
4) A study finding frequent sensitization to Candida albicans and profilins in adult eosinophilic esophagitis patients.
The purpose is to provide updated practical knowledge for physicians, though it does not replace clinical judgment
Pearls in Allergy and Immunology - February 2014 Juan Aldave
The document summarizes recent literature on allergic diseases from the journal Allergy and Annals of Allergy, Asthma and Immunology. It discusses topics such as atopic dermatitis, the atopic march, food allergy epidemiology and diagnosis, asthma phenotypes, new therapies for atopic dermatitis and allergic asthma, and the role of filaggrin mutations and phospholipids in omalizumab treatment efficacy for atopic dermatitis. The purpose is to provide updated knowledge for allergy/immunology physicians, though it does not replace clinical judgment. Any corrections or suggestions should be sent directly to the author.
The document provides an educational summary of recent literature on allergies and clinical immunology. It includes summaries of several articles: 1) "Basophils Unlimited" describes a new method for generating large quantities of mouse basophils for research; 2) "Dog Saliva" shows that dog saliva contains more diverse allergenic proteins than dander and may improve diagnostics; 3) An EAACI position paper analyzes the quality and standardization of skin prick testing solutions for occupational allergies. The summary also briefly outlines additional articles on basophil functions, the impact of intranasal corticosteroids on asthma outcomes in patients with allergic rhinitis, and low-dose aspirin desensitization
Pearls in Allergy and Immunology, January 2014Juan Aldave
The purpose of this educational material is to provide updated knowledge for Allergy/Immunology Physicians. It summarizes recent articles from peer-reviewed journals. If there are any corrections needed, they should be sent directly to the authors by email.
The document summarizes several articles from recent issues of peer-reviewed journals, including:
1) A case report of anaphylaxis induced by streptomycin skin testing, highlighting the risks of systemic reactions from skin testing.
2) An overview of aspirin-exacerbated respiratory disease and approaches to aspirin desensitization, which can effectively improve asthma and sinusitis outcomes.
3) A discussion of the low adherence rates to asthma
This educational material from Juan Carlos Aldave Becerra aims to provide updated knowledge for allergy/immunology physicians. It discusses recent studies on various topics: the potential relationship between allergic rhinitis and erectile dysfunction; the role of extracellular DNA traps in allergic, infectious and autoimmune diseases; and the identification of galactose-α-1,3-galactose in ticks which may be related to red meat allergy. It also reviews several other recent articles on topics like food allergy, drug allergy, asthma treatments and immunodeficiencies. The author welcomes any feedback to improve the educational value.
Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to the fungus Aspergillus fumigatus in patients with asthma or cystic fibrosis. It occurs in 1-2% of asthmatics and 1-15% of cystic fibrosis patients. Clinical features include recurrent asthma exacerbations, cough, wheezing and blood-stained sputum. Diagnosis is based on clinical criteria and elevated IgE levels. Treatment involves oral corticosteroids, antifungal agents like itraconazole, and omalizumab for severe cases. Prognosis depends on early diagnosis and treatment to prevent lung damage.
Severe or difficult-to-treat asthma affects approximately 15% of asthma patients and is characterized by persistent symptoms and exacerbations despite high-dose controller medications. These patients experience greater morbidity and increased healthcare use. Characteristics of severe asthma include irreversible airflow obstruction, neutrophilic inflammation, ongoing mediator release, and reduced association with atopy. Management involves accurate diagnosis, treatment of risk factors and comorbidities, appropriate medication including biologics like omeklizumab, and ongoing patient education and support.
This document discusses sublingual immunotherapy (SLIT) for food allergies. It begins by defining SLIT and comparing it to subcutaneous immunotherapy (SCIT), noting that SLIT is a non-injection route that may help increase compliance. The mechanism of SLIT is described, including how the oral mucosa has immune-privileged cells that can induce tolerance. Studies on using SLIT for peanut allergy and milk allergy are summarized, outlining their methods, results, and findings regarding increased reaction thresholds, decreased immune markers, and minimal side effects.
Asthma is a chronic inflammatory airways disease affecting over 260 million people globally. The document summarizes evidence from 142 studies on subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT) for treating allergic rhinitis and asthma. SCIT was found to significantly improve asthma and rhinitis/rhinoconjunctivitis symptoms and reduce medication use compared to placebo or standard therapy in the majority of studies. SLIT was also found to significantly improve asthma symptoms compared to placebo or standard care in all studies. Both SCIT and SLIT demonstrated effectiveness, though direct comparisons between the two methods were limited.
This document summarizes a study on the relationship between atopic dermatitis and food allergy. It notes that while some studies have found a link between food allergies exacerbating atopic dermatitis symptoms, there is disagreement between dermatologists and allergologists on this relationship. The study performed a literature review and found many more reports on the topic in allergy journals compared to dermatology journals. It concludes that food elimination diets may be appropriate for some refractory atopic dermatitis patients, especially if testing finds clinical relevance between symptoms and specific foods, but their use requires careful implementation and follow-up.
The document discusses mast cell disorders and their classification. It describes localized mastocytosis, which includes cutaneous mastocytosis subtypes like urticaria pigmentosa and diffuse cutaneous mastocytosis. Systemic mastocytosis is classified into several subtypes based on severity from indolent to aggressive forms. The pathogenesis involves mutations in the KIT gene in most cases that lead to mast cell proliferation. Clinical features can include systemic symptoms from mast cell mediators as well as dermatologic findings like the rash of urticaria pigmentosa.
Src jbbr-21-125 Dr. ihsan edan abdulkareem alsaimary PROFESSOR IN MEDICAL M...dr.Ihsan alsaimary
Dr. ihsan edan abdulkareem alsaimary
PROFESSOR IN MEDICAL MICROBIOLOGY AND MOLECULAR IMMUNOLOGY
ihsanalsaimary@gmail.com
mobile : 009647801410838
university of basrah - college of medicine - basrah -IRAQ
Food allergy has been long recognized and well documented. Other adverse reactions to foods first referred to as “toxic idiopathies” by John Freeman, co inventor of immunotherapy, at the early part of the 1900s can be mediated by and have their impact on the nervous and endocrine systems. It can also be mediated by pharmacologic mechanisms and can also affect any part of the body. There’s a great clinical need to accurately identify triggers of adverse reactivity as they have now been linked with even the most serious of modern maladies and diseases. In fact, inflammation is the hallmark of metabolic syndrome. Given the multitude of pathogenic mechanisms underlying adverse reactions to foods and other environmental exposures it is necessary that a utilizable and cost effective technology be understood so that its application be utilized under the appropriate circumstances.
KEY LEARNING POINTS
• The natural ability of certain foods to initiate an inflammatory response and induce metabolic disruptions and counterbalancing mechanisms to prevent that
• How foods can trigger “danger signals” for the immune system
Pharmacologic vs. immunologic reactions to foods
• Is there a common final pathway of all these mechanisms that can reliably indicate triggers of clinical pathology?
• Cellular testing vs. serologic testing: The advantages of cellular testing
This document discusses approaches to preventing allergic diseases in children. It mentions that allergic diseases have increased rapidly in recent decades likely due to environmental and lifestyle changes. Early life exposure to allergens and microbes may influence the development of allergic immune responses. The document discusses genetic and environmental risk factors for atopic dermatitis and reviews evidence on the role of various allergens like food, aeroallergens and bacteria. It proposes that primary prevention aims to prevent sensitization to allergens, secondary prevention prevents disease progression after sensitization and tertiary prevention reduces symptoms after disease onset through allergen avoidance and treatment.
Luis is a 9-year-old male seen for worsening itchy skin causing difficulties in school and sleep. He has had dry, itchy skin on his arms and legs for 2 years that is worse in winter. His father has asthma and rhinitis. On examination, Luis has dry skin, erythema, dryness, and scaling on his arms and legs. Managing atopic dermatitis requires addressing skin hydration, trigger avoidance, patient education, and various treatment approaches depending on severity. Patient adherence to treatment is often poor which can impact outcomes.
Alergia a los almentos mediadas por anticuerpos ig g asociadas con la migraña...MEDIAGNOSTIC
This document discusses a study investigating the presence of IgG antibodies to foods in patients with migraine refractory to traditional treatment. The study found:
1) Statistical significant differences in the number of positive IgG food allergens between patients with migraine (56 patients) and a control group without migraine.
2) Elimination diets successfully controlled migraines in patients, without the need for medications.
3) According to the results, serum IgG antibodies to common foods should be investigated in patients with migraine.
This document discusses the historical perspective, epidemiology, pathogenesis, etiology, and immune responses related to allergic bronchopulmonary aspergillosis (ABPA). It notes that ABPA was first described in 1952 and involves an allergic response to the fungus Aspergillus, which commonly involves the lungs. The document outlines the involvement of innate immune responses like TLRs and acquired responses like specific antibodies and T cells. It also examines factors like genetic variants that can influence susceptibility.
This document discusses allergies in the adult population of Pakistan. It aims to identify the most common allergy categories and factors causing different allergies by conducting skin prick tests on 377 patients visiting the Allergy Center of the National Institute of Health in Islamabad over 3 months. The study hopes to provide data on allergy prevalence in Pakistani adults and determine specific allergens linked to different allergies to inform health policy. Gaps in literature on allergies in Pakistan are also discussed due to the country facing a double disease burden and allergies being a neglected area.
This document summarizes statin-induced myopathies. It discusses statin mechanisms of action and predisposing factors. It describes different clinical phenotypes including rhabdomyolysis, myalgia with mild CK elevation, self-limited toxic myopathy, and immune-mediated necrotizing myopathy associated with anti-HMGCR antibodies. Immune-mediated necrotizing myopathy is characterized by muscle necrosis, regeneration, and scarce inflammation. Diagnosis involves detecting elevated CK, myopathic EMG findings, and anti-HMGCR antibodies. Treatment depends on severity but may include immunosuppression.
This study evaluated the efficacy and safety of intravenous injection of Mycobacterium w (Mw) in treating gram-negative sepsis.
The study involved 30 patients over 18 years of age with gram-negative sepsis and single organ dysfunction. Patients received intravenous Mw injections in addition to standard care. Results showed significant improvements in vital signs, organ function markers, and sepsis severity scores from day 2 onward compared to baseline. No major adverse events occurred.
The study concluded that intravenous Mw appears to be a well-tolerated and effective adjuvant treatment for gram-negative sepsis when added to standard care, as demonstrated by improved clinical outcomes. However, larger randomized controlled trials are still needed to confirm these findings.
The effect of vitamin D add-on therapy on the improvement of.pdfFinnyOktaria
This study evaluated the effect of add-on vitamin D therapy on quality of life and clinical symptoms in patients with chronic spontaneous urticaria. 80 patients were randomly assigned to receive either a low dose (4200 IU/week) or high dose (28000 IU/week) of vitamin D supplementation for 12 weeks. Both groups showed significantly reduced urticaria severity scores and improved quality of life. However, the high dose group showed greater improvements in scores at weeks 6 and 12. Vitamin D levels increased significantly in both groups over 12 weeks, but rose higher in the high dose group. No significant differences were seen in medication scores between groups. The results suggest add-on therapy with 28000 IU/week of vitamin D
This document summarizes several studies on the off-label use of omalizumab (anti-IgE) to treat various allergic and respiratory conditions beyond its approved use for asthma and chronic idiopathic urticaria. It also discusses other emerging biologic therapies that target specific cytokines and pathways involved in allergic inflammation and asthma pathogenesis. These include therapies targeting IL-4/IL-13 (dupilumab), IL-5 (mepolizumab, reslizumab, benralizumab), IL-17 (secukinumab, brodalumab), IL-2 (daclizumab), and thymic stromal lymphopoietin (tezepelumab). The
- NSAIDs hypersensitivity can present with distinct clinical phenotypes based on organ system involvement and timing of symptoms. It is estimated that less than 20% of reported adverse reactions to NSAIDs are true hypersensitivities.
- AERD/NERD involves eosinophilic rhinosinusitis, asthma, and nasal polyps. Exposure to aspirin or other NSAIDs exacerbates bronchospasms and rhinitis. Management involves lifelong avoidance of culprit and cross-reacting NSAIDs.
- Various phenotypes are described beyond the EAACI classification, including blended reactions involving multiple organs, food-dependent NSAID-induced anaphylaxis, and NSAID-selective immediate reactions. Proper diagnosis relies
Similar to Pearls in Allergy and Immunology, November 2013 (19)
Actualización en Inmunología, 04 de abril de 2014Juan Aldave
Este documento presenta un resumen de varios artículos recientes sobre inmunología. El primer artículo describe una mutación en el gen STAT1 encontrada en un niño con fusariosis cutánea recalcitrante. Otro artículo encuentra mutaciones en el gen CARD9 vinculadas a feohifomicosis subcutánea y deficiencias de células T TH17. Finalmente, se discuten opciones de tratamiento para urticaria crónica como el uso de omalizumab o desensibilización.
Actualización en Inmunología, 07-marzo-2014Juan Aldave
El documento presenta un programa de actualización en inmunología dirigido a médicos del Hospital Nacional Edgardo Rebagliati Martins en Perú, con el objetivo de fortalecer sus conocimientos en inmunología básica e inmunología clínica. El programa consiste en revisiones y discusiones de artículos recientes sobre inmunología con conclusiones prácticas que se llevarán a cabo cada segundo viernes de mes.
Actualización en Inmunología, 07-feb-2014Juan Aldave
Este documento presenta un programa de actualización en inmunología dirigido a médicos en el Hospital Nacional Edgardo Rebagliati Martins en Lima, Perú. El programa tiene como objetivos fortalecer los conocimientos en inmunología básica e inmunología clínica de los médicos, promover el trabajo interdisciplinario, y fomentar la investigación. Se llevará a cabo reuniones mensuales para revisar artículos recientes y casos clínicos. El contenido educativo busca brindar conocimientos actualizados sobre
1) La exposición a aeroalérgenos y agentes infecciosos activa el epitelio para secretar citocinas que generan un ambiente pro-Th2; 2) Las células dendríticas atrapan antígenos y los presentan a los linfocitos Th0 induciendo su diferenciación a Th2; 3) Los linfocitos Th2 activan a otros actores como linfocitos B para producir IgE y mastocitos, causando inflamación y síntomas alérgicos. La inmunoterapia sublingual busca educar al sistema in
Inmunomodulación en reacciones alérgicas a fármacos antituberculosis - JCJuan Aldave
La inmunomodulación puede servir para tratar reacciones adversas inmunológicas a fármacos antituberculosis. La manera de inmunomodular depende de la fisiopatología subyacente y puede incluir desensibilización, anti-IgE, inmunoglobulina intravenosa u otras opciones. Sin embargo, la inmunomodulación no siempre funciona debido a la falta de protocolos estandarizados, por lo que se requiere mayor investigación.
Generalidades sobre el diagnóstico de rinitis alérgica - JCJuan Aldave
La rinitis alérgica es una reacción de hipersensibilidad mediada por IgE frente a aeroalérgenos como ácaros y pólenes, que causa inflamación nasal y posibles complicaciones. Su diagnóstico requiere detección de IgE específica mediante pruebas cutáneas o en suero, y su tratamiento incluye evitación de alérgenos, fármacos e inmunoterapia según la gravedad de los síntomas.
El documento resume los principales factores patogénicos de la dermatitis atópica: 1) defectos en la barrera cutánea como proteínas de diferenciación epidérmica; 2) disregulación inmunitaria como respuestas TH2 elevadas y TH1/TH17 disminuidas; 3) sensibilización a antígenos extraños como ácaros y alimentos, y antígenos propios. Conocer estos factores es importante para entender, desarrollar y personalizar tratamientos para la dermatitis atópica.
Perlas en Alergia e Inmunología, Noviembre 2013Juan Aldave
Este documento presenta varios artículos recientes sobre Inmunología Clínica y Alergología. El propósito es brindar conocimiento actualizado a médicos para mejorar el diagnóstico y tratamiento de enfermedades alérgicas e inmunológicas. Se resumen estudios sobre epidemiología de la anafilaxia, desensibilización a fármacos, efecto de suplementos de aceite de pescado durante el embarazo, alérgenos en el polvo doméstico y su relación con sensibilización al maní,
Perlas en Alergia e Inmunología Octubre 2013Juan Aldave
Este documento presenta un resumen de varios artículos recientes sobre Inmunología Clínica y Alergología. Cubre temas como los factores que pueden influir en la gravedad de las reacciones anafilácticas, el diagnóstico de anafilaxia inducida por cofactores, las causas de abandono de la inmunoterapia sublingual y estrategias para mejorar la adherencia, y nuevos hallazgos sobre mastocitos, basófilos y células T en enfermedades alérgicas. El documento busca capacitar
Actualización en Inmunología 11 Octubre 2013Juan Aldave
Este documento presenta un programa de actualización en inmunología dirigido a médicos en el Hospital Nacional Edgardo Rebagliati Martins en Lima, Perú. Los objetivos son fortalecer conocimientos en inmunología básica y clínica, promover el trabajo interdisciplinario, y fomentar la investigación. El programa consiste en revisiones y discusiones de artículos recientes sobre inmunología el primer y segundo viernes de cada mes, con conclusiones prácticas. También incluye invitaciones a médicos para futuras actualiz
Actualización en Inmunología 11-Oct-2013Juan Aldave
Este documento presenta un programa de actualización en inmunología dirigido a médicos del Hospital Nacional Edgardo Rebagliati Martins en Lima, Perú. El programa tiene como objetivos fortalecer los conocimientos en inmunología básica y clínica, promover el trabajo interdisciplinario, y fomentar la investigación. El programa consiste en revisiones y discusiones de artículos recientes sobre inmunología el primer y segundo viernes de cada mes, con conclusiones prácticas y sugerencias para investigación.
Actualización en Inmunología 04-Oct-2013Juan Aldave
Este documento presenta un programa de actualización en inmunología dirigido a médicos del Hospital Nacional Edgardo Rebagliati Martins. El programa se llevará a cabo los primeros viernes de cada mes y consistirá en la revisión y discusión de artículos recientes, conclusiones prácticas, ideas para investigación y trabajo interdisciplinario. El objetivo es fortalecer los conocimientos en inmunología clínica y promover la investigación entre los servicios del departamento de especialidades médicas.
Perlas en Alergia e Inmunología Septiembre 2013Juan Aldave
Este material educativo tiene el propósito de brindar conocimientos actualizados sobre Inmunología Clínica y Alergología de manera práctica. No sustituye el criterio clínico del médico. Se prohíbe la reproducción total o parcial con fines distintos de los académicos o lucrativos. El contenido incluye resúmenes de artículos recientes sobre diversos temas como alergias alimentarias, inmunodeficiencias, asma y dermatitis atópica.
Actualización en Inmunología - 13-Set-2013Juan Aldave
Este documento presenta un programa de actualización en inmunología dirigido a médicos del Hospital Nacional Edgardo Rebagliati Martins en Lima, Perú. El programa incluye revisiones y discusiones de artículos recientes sobre inmunología con el objetivo de fortalecer los conocimientos de los médicos, promover el trabajo interdisciplinario y la investigación. Se discuten varios temas como receptores nucleares activados por lípidos, pustulosis exantemática generalizada aguda, riesgos de la obesidad, esofagitis eosinof
Actualización en Inmunología 06-09-2013Juan Aldave
Este documento presenta un programa de actualización en inmunología en el Hospital Nacional Edgardo Rebagliati Martins en Lima, Perú. El programa tiene como objetivos fortalecer y actualizar conocimientos en inmunología básica y clínica entre los médicos, y promover la investigación e interdisciplinariedad. Se llevará a cabo reuniones mensuales para revisar artículos recientes y casos clínicos con el fin de brindar conocimiento actualizado sobre inmunología clínica y alergología.
2013 agosto - Perlas en Alergia e InmunologíaJuan Aldave
Este documento presenta un resumen de varios artículos recientes sobre Inmunología Clínica y Alergología con el propósito de brindar conocimiento actualizado a los médicos. Incluye casos clínicos, estudios y revisiones sobre temas como policondritis recidivante, alergia a venenos de himenópteros, reacción a medicamentos para TDAH manifestada como tos crónica, comparación de la biodisponibilidad de epinefrina de diferentes autoinyectores y más. El contenido no sustituye el criterio clínico del médico
Actualización en Alergia e Inmunología 16/08/2013Juan Aldave
Este documento presenta un programa de actualización en inmunología en el Hospital Nacional Edgardo Rebagliati Martins en Lima, Perú. El objetivo es fortalecer y actualizar los conocimientos de los médicos en inmunología básica e inmunología clínica a través de revisiones y discusiones de artículos recientes. El programa se llevará a cabo los primeros viernes de cada mes para promover el trabajo interdisciplinario y la investigación.
Actualización en Inmunología - 02 de agosto de 2013Juan Aldave
El documento describe un programa de actualización en inmunología en el Hospital Nacional Edgardo Rebagliati Martins en Lima, Perú. El programa tiene como objetivos fortalecer y actualizar conocimientos en inmunología básica e inmunología clínica entre los médicos, promover el trabajo interdisciplinario, y fomentar la investigación. Se llevará a cabo revisión y discusión de artículos recientes los primeros viernes de cada mes para compartir conclusiones prácticas y nuevas ideas.
Adhd Medication Shortage Uk - trinexpharmacy.comreignlana06
The UK is currently facing a Adhd Medication Shortage Uk, which has left many patients and their families grappling with uncertainty and frustration. ADHD, or Attention Deficit Hyperactivity Disorder, is a chronic condition that requires consistent medication to manage effectively. This shortage has highlighted the critical role these medications play in the daily lives of those affected by ADHD. Contact : +1 (747) 209 – 3649 E-mail : sales@trinexpharmacy.com
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
Promoting Wellbeing - Applied Social Psychology - Psychology SuperNotesPsychoTech Services
A proprietary approach developed by bringing together the best of learning theories from Psychology, design principles from the world of visualization, and pedagogical methods from over a decade of training experience, that enables you to: Learn better, faster!
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
Osteoporosis - Definition , Evaluation and Management .pdfJim Jacob Roy
Osteoporosis is an increasing cause of morbidity among the elderly.
In this document , a brief outline of osteoporosis is given , including the risk factors of osteoporosis fractures , the indications for testing bone mineral density and the management of osteoporosis
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
1. November 2013
General considerations:
• The purpose of this educational material is exclusively
educational, to provide practical updated knowledge
for Allergy/Immunology Physicians.
• The content of this educational material does not
intend to replace the clinical criteria of the physician.
• If there is any correction or suggestion to improve the
quality of this educational material, it should be done
directly to the author by e-mail.
• If there is any question or doubt about the content of
this educational material, it should be done directly to
the author by e-mail.
Juan Carlos Aldave Becerra, MD
Allergy and Clinical Immunology
Hospital Nacional Edgardo Rebagliati Martins, Lima-Peru
jucapul_84@hotmail.com
Juan Félix Aldave Pita, MD
Medical Director
Luke Society International, Trujillo-Peru
2. Juan Carlos Aldave Becerra, MD
Allergy and Clinical Immunology
Rebagliati Martins National Hospital, Lima-Peru
November 2013 – content:
•
THE EPIDEMIOLOGY OF ANAPHYLAXIS IN EUROPE: A SYSTEMATIC REVIEW (Panesar SS, Javad S, de
Silva D, Nwaru BI, Hickstein L, Muraro A, Roberts G, Worm M, Bil o MB, Cardona V, Dubois AEJ, Dunn Galvin
A, Eigenmann P, Fernandez-Rivas M, Halken S, Lack G, Niggemann B, Santos AF, Vlieg-Boerstra BJ, Zolkipli
ZQ & Sheikh A on behalf of the EAACI Food Allergy and Anaphylaxis Group. Allergy 2013; 68: 1353–1361).
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RAPID DESENSITIZATION TO CHEMOTHERAPY AND MONOCLONAL ANTIBODIES IS EFFECTIVE AND
SAFE (Giavina-Bianchi P, Caiado J, Picard M, Pur Ozyigit L, Mezzano V, Castells M. Allergy 2013; 68: 1482–
1484).
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RANDOMIZED CONTROLLED TRIAL OF FISH OIL SUPPLEMENTATION IN PREGNANCY ON
CHILDHOOD ALLERGIES (Palmer DJ, Sullivan T, Gold MS, Prescott SL, Heddle R, Gibson RA, Makrides M.
Allergy 2013; 68: 1370–1376).
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PEANUT ALLERGEN IN HOUSE DUST OF EATING AREA AND BED – A RISK FACTOR FOR PEANUT
SENSITIZATION? (Trendelenburg V, Ahrens B, Wehrmann A-K, Kalb B, Niggemann B, Beyer K. Allergy 2013;
68: 1460–1462).
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DIVERSITY OF ALLERGENS CONTAINED IN DOG SALIVA (Codina R. Allergy 2013; 68: 1484–1485).
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ASPIRIN 300 MG/DAY IS EFFECTIVE FOR TREATING ASPIRIN-EXACERBATED RESPIRATORY
DISEASE (Comert S, Celebioglu E, Yucel T, Erdogan T, Karakaya G, Onerci M, Kalyoncu AF. Allergy 2013;
68: 1443–1451).
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AIRWAY DYSFUNCTION IN ELITE ATHLETES – AN OCCUPATIONAL LUNG DISEASE? (Price OJ, Ansley
L, Menzies-Gow A, Cullinan P, Hull JH. Allergy 2013; 68: 1343–1352).
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DELAYED ANAPHYLAXIS SECONDARY TO ALLERGY SKIN TESTING (Ricketti PA, Unkle DW, Cleri DJ,
Ricketti AJ. Ann Allergy Asthma Immunol 2013; 111: 420-421).
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OVER-THE-COUNTER INTRANASAL CORTICOSTEROIDS: WHY THE TIME IS NOW (Blaiss MS. Ann
Allergy Asthma Immunol 2013; 111: 316-318).
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RISK OF ADVERSE EFFECTS, MISDIAGNOSIS, AND SUBOPTIMAL PATIENT CARE WITH THE USE OF
OVER-THE-COUNTER TRIAMCINOLONE (Friedlander SL, Tichenor WS, Skoner DP. Ann Allergy Asthma
Immunol 2013; 111: 319-322).
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SHORT-TERM OMALIZUMAB TREATMENT IN AN ADOLESCENT WITH CUTANEOUS MASTOCYTOSIS
(Matito A, Blázquez-Goñi C, Morgado JM, Álvarez-Twose I, Mollejo M, Sánchez-Muñoz L, Escribano L. Ann
Allergy Asthma Immunol 2013; 111: 425-426).
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THE BURDEN OF ILLNESS IN PATIENTS WITH HEREDITARY ANGIOEDEMA (Banerji A. Ann Allergy
Asthma Immunol 2013; 111: 329-336).
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ATOPIC DERMATITIS: SCRATCHING THROUGH THE COMPLEXITY OF BARRIER DYSFUNCTION
(Sprecher E, Leung DYM. J Allergy Clin Immunol 2013; 132: 1130-1131).
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CODING-REGION ALTERATIONS IN BTK DO NOT UNIVERSALLY CAUSE X-LINKED
AGAMMAGLOBULINEMIA (Abbott JK, Ochs HD, Gelfand EW. J Allergy Clin Immunol 2013; 132: 1246-1248).
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EOSINOPHILIC ASTHMA: INSIGHTS INTO THE EFFECTS OF REDUCING IL-5 RECEPTOR–POSITIVE
CELL LEVELS (Assa’ad AH, Rothenberg ME. J Allergy Clin Immunol 2013; 132: 1097-1098).
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GLUCOCORTICOID-INDUCED OSTEOPOROSIS: AN UPDATE ON EFFECTS AND MANAGEMENT
(Buehring B, Viswanathan R, Binkley N, Busse W. J Allergy Clin Immunol 2013; 132: 1019-1030).
PEARLS IN ALLERGY AND IMMUNOLOGY
November 2013
3. The purpose of this summary is exclusively educational, to provide practical updated knowledge for Allergy/Immunology Physicians. It does not
intend to replace the clinical criteria of the physician.
•
OUTCOMES OF THE CHILDHOOD ASTHMA PREVENTION STUDY AT 11.5 YEARS (Toelle BG, Garden
FL, Ng KKW, Belousova EG, Almqvist C, Cowell CT, Tovey ER, Webb KL, Leeder SR, Marks GB. J Allergy
Clin Immunol 2013; 132: 1220-1222).
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REGIONAL DIFFERENCES IN THE EXPRESSION OF INNATE HOST DEFENSE MOLECULES IN
SINONASAL MUCOSA (Seshadri S, Rosati M, Lin DC, Carter RG, Norton JE, Choi AW, Suh L, Kato A,
Chandra RK, Harris KE, Chu HW, Peters AT, Tan BK, Conley DB, Grammer LC, Kern RC, Schleimer RP. J
Allergy Clin Immunol 2013; 132: 1220-1222).
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RHINOVIRUS SPECIFIC IGE CAN BE DETECTED IN HUMAN SERA (Tam JS, Jackson WT, Hunter D, Proud
D, Grayson MH. J Allergy Clin Immunol 2013; 132: 1241-1243).
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THE BIOLOGY OF THE GLUCOCORTICOID RECEPTOR: NEW SIGNALING MECHANISMS IN HEALTH
AND DISEASE (Oakley RH, Cidlowski JA. J Allergy Clin Immunol 2013; 132: 1033-1044).
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THE EDITORS’ CHOICE (Leung DYM, Szefler SJ. J Allergy Clin Immunol 2013; 132: 1056-1057).
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THE LONG ROAD TO OPTIMAL MANAGEMENT FOR CHRONIC GRANULOMATOUS DISEASE
(Notarangelo LD. J Allergy Clin Immunol 2013; 132: 1164-1165).
•
USE OF ONDANSETRON FOR FOOD PROTEIN–INDUCED ENTEROCOLITIS SYNDROME (Holbrook T,
Keet, CA, Frischmeyer-Guerrerio PA, Wood RA. J Allergy Clin Immunol 2013; 132: 1219-1220).
“But knowledge puffs up while love builds up” 1 Corinthians 8:1
4. Juan Carlos Aldave Becerra, MD
Allergy and Clinical Immunology
Rebagliati Martins National Hospital, Lima-Peru
ALLERGY:
•
AIRWAY DYSFUNCTION IN ELITE ATHLETES – AN OCCUPATIONAL LUNG DISEASE? (Price
OJ, Ansley L, Menzies-Gow A, Cullinan P, Hull JH. Allergy 2013; 68: 1343–1352):
•
•
Exercise-induced bronchoconstriction: (i) definition: transient, reversible bronchoconstriction
after exercise; (ii) prevalence: occurs in 90% of asthmatics, 50% of elite athletes and 15% of the
general population; (iii) diagnosis: clinical history, exercise challenge (↓ 10-15% of FEV1 within
30 min after exercise; exercise at suboptimal intensity/duration or with warm/humid inspired air
may cause false-negative results), mannitol challenge.
•
Mechanisms of EIB: (i) heating and humidifying large volumes of air in a short period → loss of
water from the lower airways → hyperosmolar environment → activation and release of
mediators (cysLTs, PGD2, ECP, adenosine, neurokinins, MUC5AC) from mast cells,
eosinophils, epithelial cells and nerves → bronchoconstriction; (ii) very intense exercise in
athletes → dehydration injury to the airway epithelium → microvascular leak and plasma
exudation → bronchoconstriction; (iii) hyperpnoea → exposure to greater quantities of
aeroallergens and pollutants.
•
A 20-min warm-up at submaximal intensity or 30-sec repeated sprints cause refractoriness to
following vigorous exercise (hypothesis: ↓ mast cell mediator stores, ↑ protective
prostaglandins, desensitization of airway smooth muscle receptors to mediators).
•
Risk factors for EIB: dry air, cold air, high load of aeroallergens and pollutants, high ventilation,
mouth breathing.
•
Strategies to ↓ airway dysfunction in athletes: (i) early proper diagnosis; (ii) sport environments
with less concentration of aeroallergens and pollutants; (iii) warming up before exercise; (iv) use
of β2-agonists before exercise (risk of adverse effects and tachyphylaxis); (v) use of daily
inhaled corticosteroids; (vi) dietary modification (e.g. fish oil supplementation).
•
•
Airway dysfunction: frequent problem in elite athletes (both summer and winter high-intensity
sports); impact: affects their performance and health.
Elite athletes should receive the same considerations for their airway health as others with
relevant occupational exposures.
ASPIRIN 300 MG/DAY IS EFFECTIVE FOR TREATING ASPIRIN-EXACERBATED
RESPIRATORY DISEASE (AERD) (Comert S, Celebioglu E, Yucel T, Erdogan T, Karakaya G,
Onerci M, Kalyoncu AF. Allergy 2013; 68: 1443–1451):
•
NSAID hypersensitivity: (i) intolerance: pharmacologic mechanism (COX inhibition); crossreactivity; urticaria/angioedema is the most frequent reaction; (ii) allergy: IgE or T-cell mediated;
selective reactivity; less frequent.
•
Traditional management of intolerance to NSAIDs: (i) avoidance of COX-1 inhibitors; (ii) use of
selective COX-2 inhibitors as alternative drugs (usually well tolerated); (iii) desensitization to
aspirin (effective but requires continuous therapy; tolerance disappears within 2 to 5 days after
NSAID interruption).
PEARLS IN ALLERGY AND IMMUNOLOGY
November 2013
5. The purpose of this summary is exclusively educational, to provide practical updated knowledge for Allergy/Immunology Physicians. It does not
intend to replace the clinical criteria of the physician.
•
•
Authors performed aspirin desensitization in 40 patients with AERD (maintenance dose = 300
mg/day) → (i) 29 patients continued treatment for ≥1 year, 18 patients for ≥3 yrs; (ii) beneficial
effects of desensitization (up to 3 yrs of follow up): ↓ systemic corticosteroid use, ↓ episodes of
sinusitis, ↓ surgery requirement.
•
•
AERD (Samter’s triad): (i) clinical manifestations: intolerance to NSAIDs, nasal polyposis,
chronic eosinophilic sinusitis, severe asthma; (ii) prevalence: 0.5% of the general population,
15% of asthmatics, 35% of asthmatics with nasal polyposis; (iii) treatment option for severe
cases: aspirin desensitization (optimal maintenance dose is controversial; some authors
recommend ≥325 mg bid, however, even doses of 325 mg/day are associated with a
considerable risk of GI bleeding).
Author’s commentary: treatment with aspirin 300 mg/day was beneficial in patients with AERD.
DIVERSITY OF ALLERGENS CONTAINED IN DOG SALIVA (Codina R. Allergy 2013; 68: 1484–
1485):
•
•
Polovic et al (Allergy 2013; 68: 585–592) → (i) dog saliva has a greater number and diversity of
allergenic proteins compared to dog dander (e.g. BPIFA2, Mucin-5B, ANGPTL5, IgA heavy
chain constant region); (ii) allergenic proteins in dog saliva vary among dog breeds; (iii) dog
saliva extracts may improve diagnostics of dog allergy.
•
•
Pet allergy: (i) pet allergens are found in a variety of sources (e.g. dander, hair, epithelium,
saliva, urine); (ii) most cat-allergic individuals react to Fel d 1 (standardized cat extracts are
based on Fel d 1 concentrations); (iii) a distinctive major dog allergen has not been identified
(different allergens are relevant in different patients); (iv) dander is the most common material
used for the preparation of dog allergenic extracts; (v) there are patients with dog allergy who
have negative tests to dog dander extracts; (vi) dog dander extracts might be contaminated with
mite allergens (could lead to false positive SPT results).
It might be difficult to standardize allergenic extracts from dog saliva.
PEANUT ALLERGEN IN HOUSE DUST OF EATING AREA AND BED – A RISK FACTOR FOR
PEANUT SENSITIZATION? (Trendelenburg V, Ahrens B, Wehrmann A-K, Kalb B, Niggemann B,
Beyer K. Allergy 2013; 68: 1460–1462):
•
•
•
IgE-mediated peanut allergy: (i) impact: significant morbidity and mortality, ↓ QoL; (ii) diagnosis:
SPT, serum specific IgE detection, food challenge; (iii) conventional treatment: avoidance (does
not prevent accidental exposure), autoinjectable epinephrine, nutritional counseling; (iv) optimal
treatment: restore tolerance to allergens (immunotherapy).
Proposed risk factor to develop peanut allergy: consumption of peanut by the infant´s family →
high levels of peanut protein in the house (including areas where peanut is usually not
consumed [e.g. bed], indicating a spreading of allergens) → IgE-sensitization through the
infant’s skin, especially in patients with defective skin barrier (e.g. atopic dermatitis).
RANDOMIZED CONTROLLED TRIAL OF FISH OIL SUPPLEMENTATION IN PREGNANCY ON
CHILDHOOD ALLERGIES (Palmer DJ, Sullivan T, Gold MS, Prescott SL, Heddle R, Gibson RA,
Makrides M. Allergy 2013; 68: 1370–1376):
“But knowledge puffs up while love builds up” 1 Corinthians 8:1
6. Juan Carlos Aldave Becerra, MD
Allergy and Clinical Immunology
Rebagliati Martins National Hospital, Lima-Peru
•
•
Immune tolerance is essential to prevent: (i) self-destruction; (ii) inflammatory response to
beneficial or harmless exogenous molecules (e.g. food, commensal bacteria, allergens).
•
Loss of immune tolerance → allergic or autoimmune disorders.
•
Factors that promote tolerance: (i) ↑ tolerogenic microbiota (Lactobacillus, Bifidobacterium); (ii)
↑ tolerogenic dendritic cells; (iii) ↑ tolerogenic molecules (retinoic acid, TGF-β, TSLP,
indoleamine-2,3-dioxygenase, IL-10, IgG4, IgA); (iv) ↑ T regulatory responses (CD4+CD25+
Tregs, Th3 cells, Tr1 cells, CD8+ Tregs, regulatory B cells); (v) balanced TH1 responses.
•
Early interventions to induce immunologic tolerance and ↓ allergic diseases (efficacy is
controversial or not fully established): (i) use of probiotics; (ii) use of prebiotics; (iii) use of
bacterial lysates; (iv) supplements of vit D; (v) supplements of n-3 long chain polyunsaturated
fatty acids (LCPUFA) from fatty fish and fish oils.
•
Authors gave n-3 LCPUFA supplementation (900 mg/day) to pregnant women from 21 weeks’
gestation until birth → their infants were evaluated at 1 and 3 yrs of age → there was a
nonsignificant reduction (up to 22%) in IgE-mediated allergic diseases compared to controls
(the study was powered to detect a 33% relative reduction).
•
•
Immune tolerance: nonresponsiveness of the adaptive immune system or active Treg response
to antigens; mechanisms: anergy or deletion of reactive lymphocytes, generation of Treg cells.
Author’s commentaries: (i) n-3 LCPUFA supplementation during pregnancy did not significantly
reduce IgE-mediated allergies in the first 3 yrs of life; (ii) the nonsignificant risk reduction of up
to 22% may still be of public health significance (the burden of allergic disease is high while fish
oil intervention is safe and relatively cheap).
RAPID DESENSITIZATION TO CHEMOTHERAPY AND MONOCLONAL ANTIBODIES IS
EFFECTIVE AND SAFE (Giavina-Bianchi P, Caiado J, Picard M, Pur Ozyigit L, Mezzano V, Castells
M. Allergy 2013; 68: 1482–1484):
•
Drug desensitization: (i) essential procedure to manage drug-allergic patients who need the
culprit drug obligatorily; (ii) frequently necessary in patients with allergy to chemotherapy drugs
and monoclonal antibodies.
•
Madrigal-Burgaleta et al (Allergy 2013; 68: 853–861) reported the outcomes of 189
desensitization procedures to antineoplastic agents (oxaliplatin, carboplatin, paclitaxel,
docetaxel, cyclophosphamide, rituximab) in 23 patients (mean age=56 yrs) → (i) the novel
desensitization protocol lasted ~4 hrs, with a high starting dose compared to other protocols; (ii)
desensitization candidates were carefully elected by anamnesis, skin testing, risk assessment
and graded challenge; (iii) 188 desensitizations were successful (1 patient revoked consent
after a breakthrough reaction); (iv) 177 (94%) desensitizations had no breakthrough reactions; 8
desensitizations had mild reactions; 4 desensitizations had moderate/severe reactions; no
deaths; (v) 11 patients had a reaction during their 1st desensitization (premedication
[montelukast + acetylsalicylic acid] was useful to complete 2nd desensitizations, except for one
oxaliplatin-reactive patient who needed additional steps); (vi) oxaliplatin skin testing had poor
negative predictive value; (vii) specific IgE to oxaliplatin (ImmunoCAP) had 54% sensitivity
(cutoff point=0.10 UI/l) and 100% specificity in 10 oxaliplatin-reactive patients; (viii) 2 patients
had positive skin tests to paclitaxel.
PEARLS IN ALLERGY AND IMMUNOLOGY
November 2013
7. The purpose of this summary is exclusively educational, to provide practical updated knowledge for Allergy/Immunology Physicians. It does not
intend to replace the clinical criteria of the physician.
•
•
•
Author’s commentary: the desensitization protocol reported by Madrigal-Burgaleta et al might
be risky because of the high starting dose.
EAACI Drug Allergy Interest Group → needs for improving drug desensitization protocols: (i)
multicenter clinical trials with standardized and well-characterized patients; (ii) comparison of
different protocols in one well-characterized patient group; (iii) comparison of one protocol in
various, well-characterized patient groups.
THE EPIDEMIOLOGY OF ANAPHYLAXIS IN EUROPE: A SYSTEMATIC REVIEW (Panesar SS,
Javad S, de Silva D, Nwaru BI, Hickstein L, Muraro A, Roberts G, Worm M, Bil o MB, Cardona V,
Dubois AEJ, Dunn Galvin A, Eigenmann P, Fernandez-Rivas M, Halken S, Lack G, Niggemann B,
Santos AF, Vlieg-Boerstra BJ, Zolkipli ZQ & Sheikh A on behalf of the EAACI Food Allergy and
Anaphylaxis Group. Allergy 2013; 68: 1353–1361):
•
Anaphylaxis: (i) acute severe multisystemic allergic reaction; (ii) potentially fatal; (iii) caused by
the release of chemical mediators from mast cells and basophils.
•
Authors present a systematic review (49 selected studies) describing the epidemiology of
anaphylaxis in Europe (frequency, risk factors, outcomes).
•
Important points about anaphylaxis: (i) incidence seems to be increasing; (ii) incidence rate: ~1
per 20,000 person-yrs (0-4 yr-old children have higher incidence rates); (iii) lifetime prevalence:
0.3% of the population; (iv) case fatality ratio: <0.0001%; (v) most common triggers: foods,
drugs, stinging insects, latex; (vi) important comorbidities: atopic dermatitis, asthma, allergic
rhinitis, food allergy.
“But knowledge puffs up while love builds up” 1 Corinthians 8:1
8. Juan Carlos Aldave Becerra, MD
Allergy and Clinical Immunology
Rebagliati Martins National Hospital, Lima-Peru
ANNALS OF ASTHMA, ALLERGY & IMMUNOLOGY:
•
DELAYED ANAPHYLAXIS SECONDARY TO ALLERGY SKIN TESTING (Ricketti PA, Unkle DW,
Cleri DJ, Ricketti AJ. Ann Allergy Asthma Immunol 2013; 111: 420-421):
•
•
•
Authors report the case of a 59-yr-old man with asthma (medication: daily beclomethasone, as
needed albuterol), seasonal allergic rhinitis (medication: as needed antihistamines) and
hypertension (medication: valsartan, aspirin) → skin prick tests (SPT) with commercial extracts
were highly positive to grass pollens, tree pollens and dust mites → 2 hrs after SPT the patient
had signs of symptoms of anaphylaxis at home (burning and itching of the palms, nasal
congestion, itchy eyes, facial angioedema and erythema, diffuse urticaria, wheezing, throatclosing sensation, tachypnea, tachycardia); no food or drug intake during this 2-hr interval;
serum tryptase was not measured → successful treatment in the emergency department:
diphenhydramine, intravenous corticosteroids, famotidine (epinephrine was not administered).
Author’s commentaries: (i) SPT are usually safe; (ii) SPT have a minimal potential risk to cause
anaphylaxis (overall risk <0.02%); (iii) risk factors for systemic reactions after SPT: uncontrolled
asthma, concomitant use of certain drugs (e.g. ACE inhibitors), testing with foods, drugs or
Hymenoptera venoms, (iv) deaths after intradermal testing have been reported; (v) after SPT,
patients should be educated on signs and symptoms of anaphylaxis.
OVER-THE-COUNTER (OTC) INTRANASAL CORTICOSTEROIDS: WHY THE TIME IS NOW
(Blaiss MS. Ann Allergy Asthma Immunol 2013; 111: 316-318):
•
•
•
July 31, 2013 → the FDA’s Nonprescription Drugs Advisory Committee approved the switch of
Nasacort AQ (triamcinolone acetonide nasal spray) to OTC status for the same indications and
ages as it is used as a prescription product → FDA has approved the petition on October 11.
Arguments in favor of OTC use: (i) triamcinolone acetonide nasal spray is already approved for
OTC use in 11 countries, including Australia, New Zealand, Finland, Norway, Sweden,
Switzerland, Denmark, Uruguay, Malaysia and Malta; (ii) every country in the European Union
has different intranasal corticosteroid (INS) brands available for OTC use; (iii) FDA has already
approved 1st- and 2nd-generation antihistamines, oral and topical decongestants, and intranasal
cromolyn sodium for OTC use; (iv) patients in many parts of the world have been using INSs
without medical supervision for almost 20 yrs; (v) since launch, 50 million bottles of
triamcinolone acetonide nasal spray have been distributed in the US, with an excellent safety
profile (most common adverse effects: nasal dryness, nasal irritation, mild epistaxis, changes in
taste and smell); (vi) serious local adverse effects of INS (e.g. nasal septal perforation) are
extremely rare; (vii) systemic adverse effects of INS (e.g. adrenal suppression, growth
retardation) are usually non significant; (viii) patients with allergic rhinitis would have easier
access to INS (1st-line therapy); (ix) costs for the patient could be reduced (more competition
between INS-producing companies, no payment for medical consultation, no time loss for
medical consultation); (x) most patients are able to use INS appropriately; (xi) patients and
guardians could be advertised in the labeling about possible adverse effects of INS; (xii)
patients could request medical advice when INS use fails; (xiii) currently, some patients do not
receive the INS brand indicated by the physician due to insurance issues.
RISK OF ADVERSE EFFECTS, MISDIAGNOSIS, AND SUBOPTIMAL PATIENT CARE WITH THE
USE OF OVER-THE-COUNTER TRIAMCINOLONE (Friedlander SL, Tichenor WS, Skoner DP. Ann
Allergy Asthma Immunol 2013; 111: 319-322):
PEARLS IN ALLERGY AND IMMUNOLOGY
November 2013
9. The purpose of this summary is exclusively educational, to provide practical updated knowledge for Allergy/Immunology Physicians. It does not
intend to replace the clinical criteria of the physician.
•
•
•
July 31, 2013 → the FDA’s Nonprescription Drugs Advisory Committee approved the switch of
Nasacort AQ (triamcinolone acetonide nasal spray) to OTC status for the same indications and
ages as it is used as a prescription product → FDA has approved the petition on October 11.
Arguments against OTC use: (i) use of INS for wrong diagnosis, delaying treatment of other
conditions; (ii) use of INS devices in a wrong manner; (iii) lack of medical supervision of INS
serious adverse effects (nasal perforation, severe epistaxis, Candida infection, ↑ intraocular
pressure, cataracts, adrenal suppression, ↓ growth velocity, ↑ bone resorption, adverse
metabolic effects); (iv) although serious adverse effects of INS are rare, there are sensitive
subjects who would be at high risk for OTC use; (v) systemic adverse effects of OTC INS could
be potentiated by concomitant use of inhaled or skin-applied corticosteroids; (vi) very-long-term
safety of INS is not fully established; (vii) unawareness of drug-drug interactions (e.g. ritonavir
or itraconazole may ↑ triamcinolone levels; triamcinolone may ↓ efficacy of tretinoin;
fluoroquinolones + INS may ↑ risk of tendon rupture); (viii) patients may expect immediate relief
after using OTC INS (confusion with OTC topical decongestants), which might lead to INS
overuse; (ix) patients or guardians may not read or comprehend INS package labeling.
SHORT-TERM OMALIZUMAB TREATMENT IN AN ADOLESCENT WITH CUTANEOUS
MASTOCYTOSIS (Matito A, Blázquez-Goñi C, Morgado JM, Álvarez-Twose I, Mollejo M, SánchezMuñoz L, Escribano L. Ann Allergy Asthma Immunol 2013; 111: 425-426):
•
•
Authors report the case of a girl with cutaneous mastocytosis from birth (skin biopsy: severe
mast cell infiltration) → 7 yrs of age: daily pruritus and diarrhea, recurrent severe asthma
attacks, serum tryptase=15.4 ng/mL; good response to antihistamines, cromoglycate and ICS
→ 12 yrs of age: severe idiopathic urticaria/angioedema, recurrent anaphylaxis, serum basal
tryptase=8.57 ng/mL, total IgE= 508 kU/L, sIgE to D pteronyssinus= 56.9 kU/L, skin biopsy:
mastocytosis (less MC infiltration compared to biopsy at birth), parents refused bone marrow
study → incomplete response to conventional treatment (antihistamines, cromoglycate, highdose ICS/LABA, prednisone 1 mg/kg/day) → successful treatment (patient’s weight=76 kg):
omalizumab 450 mg every 4 wks for 3 doses (complete response 48 hrs after the 1st injection,
total discontinuation of other therapies in 2 months, no symptoms up to 12 months of follow-up).
•
•
Omalizumab: (i) anti-IgE mAb → binds to free IgE → ↓ IgE binding to its receptors, ↓
expression of IgE receptors → ↓ IgE-mediated inflammation; (ii) approved for [uncontrolled
asthma + serum IgE levels between 30 and 700 IU/mL + sensitization to perennial allergens];
(iii) dose is calculated in a chart, based on pretreatment IgE levels (between 30 and 700 IU/mL)
and body weight; (iv) alternative formula when the chart is not suitable: ≥0.016 mg/kg per IgE
unit every 4-wk period; (v) suggested maximum dose: 750 mg every 4 wks; (vi) efficacy has
also been documented in patients with chronic urticaria, mastocytosis, idiopathic anaphylaxis,
exercise-induced anaphylaxis, eosinophilic chronic rhinosinusitis.
Author’s commentaries: (i) cutaneous mastocytosis might be successfully treated with shortterm courses of omalizumab; (ii) larger studies are needed to confirm this beneficial effect.
THE BURDEN OF ILLNESS IN PATIENTS WITH HEREDITARY ANGIOEDEMA (Banerji A. Ann
Allergy Asthma Immunol 2013; 111: 329-336):
•
Metabolism of bradykinin (BK): FXII converts prekallikrein intro kallikrein → kininogenases
(kallikrein, FXII, plasmin) convert high-molecular-weight-kininogen into BK → BK acts through
“But knowledge puffs up while love builds up” 1 Corinthians 8:1
10. Juan Carlos Aldave Becerra, MD
Allergy and Clinical Immunology
Rebagliati Martins National Hospital, Lima-Peru
type 1 and type 2 BK receptors → BK is catabolized mainly by kininases (angiotensinconverting enzyme [ACE], aminopeptidase P [APP], carboxypeptidase N [CPN]).
•
C1-inhibitor (C1-INH) deficiency or dysfunction (autosomal dominant mutations in the
SERPING1 gene; de novo mutations occur in ~25% of cases) → ↑ activity of FXII and kallikrein
→ ↑ production of BK → ↑ endothelial permeability → ↑ vascular leakage → hereditary
angioedema (HAE): recurrent angioedema without urticaria, painful, unpredictable, potentially
fatal (markedly affects patient’s QoL).
•
Hereditary angioedema (HAE): (i) type I (85% of cases): ↓ C1-INH levels; (ii) type II (15% of
cases): normal C1-INH levels, ↓ C1-INH function; (iii) type III (very rare): normal C1-INH levels
and function, positive family history, more frequent in women, associated to high estrogen
levels, FXII mutations may contribute to pathogenesis (20-30% of cases).
•
Epidemiology of HAE: (i) prevalence: 1/50,000 subjects; (ii) age of onset: 50% of cases by 10
yrs of age, nearly all cases by 20 yrs of age; (iv) diagnosis delay: 8 yrs in average; (v) >50% of
patients may experience a life-threatening attack; (vi) many patients receive ineffective
treatment and unnecessary medical procedures before diagnosis.
•
HAE attacks: (i) clinical manifestations (severity is variable): nonpruritic painful angioedema
without urticaria, abdominal pain, vomiting, nausea, constipation, diarrhea, throat tightness,
circulatory collapse, loss of consciousness; (ii) most common sites: skin, GI tract (>50% of
patients may experience ≥1 laryngeal attack); (iii) prodromal symptoms: erythema marginatum;
(iv) frequency average (if untreated): 1 attack every 10 days; (v) duration average: 2-5 days; (vi)
peak of symptoms: 12-36 hrs; (vii) possible triggers (do not always occur): physical trauma,
medical procedures (e.g. surgery), infection, emotional stress, drugs (e.g. ACE inhibitors,
estrogens); (viii) pregnancy might aggravate or reduce attacks.
•
Drugs to treat HAE attacks: (i) plasma-derived or recombinant human C1-INH; (ii) ecallantide
(inhibitor of kallikrein); (iii) icatibant (bradykinin receptor antagonist). For the 3 agents, many
patients improve in <30 min, 75% of patients improve in <4 hrs, complete alleviation is often
achieved in 8-12 hrs (none of the therapies completely control symptoms in every patient).
Good safety profile for the 3 agents (3% risk of anaphylaxis with ecallantide).
•
Drugs to prevent HAE attacks: (i) attenuated androgens: low price; considerable dosedependent side effects; usually contraindicated in children, pregnancy and breastfeeding; (ii)
plasma-derived C1-INH replacement therapy: good safety profile; very expensive (highest
annual cost of any drug in the US); reduce 50% of attacks; (iii) tranexamic acid: agent of choice
in children, rarely contraindicated (e.g. thrombophilia).
PEARLS IN ALLERGY AND IMMUNOLOGY
November 2013
11. The purpose of this summary is exclusively educational, to provide practical updated knowledge for Allergy/Immunology Physicians. It does not
intend to replace the clinical criteria of the physician.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY:
•
ATOPIC DERMATITIS: SCRATCHING THROUGH THE COMPLEXITY OF BARRIER
DYSFUNCTION (Sprecher E, Leung DYM. J Allergy Clin Immunol 2013; 132: 1130-1131):
•
Atopic dermatitis (AD): common chronic skin disease (3% of adults, 20% of children); impact: ↓
QoL, ↑ predisposition to skin infections (bacterial, viral) and other allergies (asthma, allergic
rhinitis); pathogenic factors are multiple (genetic, epigenetic, environmental) and may result in
varied clinical phenotypes.
•
Pathogenic factors for AD: (i) skin barrier defects: scratching, ↓ synthesis of epidermal proteins
(e.g. filaggrin, loricrin, involucrin, corneodesmosin, S100 proteins, proteases, antiproteases [e.g.
LEKTI], tight junction proteins [e.g. claudin-1]) due to genetic mutations or TH2-cytokine
influence → increased entry of allergens through skin.
•
(ii) innate immune dysregulation: ↑ inflammatory dendritic cells, altered TLR signalling, ↓
production of antimicrobial peptides (e.g. cathelicidin, defensins), ↑ keratinocyte production of
cytokines that promote TH2 environment (e.g. TSLP, IL-25, IL-33), ↑ production of
neuropeptides (AD is usually associated with stress).
•
(iii) adaptive immune dysregulation (determined by genetic factors [e.g. polymorphisms in
IL4RA] and environmental factors [e.g. Staphylococcal superantigens, allergens, low vit D]): ↑
TH2 inflammation (IL-4, IL-13, IL-5, IgE, IL-31 → promote skin barrier dysfunction and pruritus),
↑ TH22 inflammation (promotes acanthosis), altered TH1 responses (predisposition to viral and
bacterial infections), altered TH17 responses (predisposition to bacterial and fungal infections),
↓ Treg responses.
•
(iv) exaggerated immune responses to food allergens (e.g. milk, egg), aeroallergens (e.g.
house dust mites), microbial molecules (e.g. from S aureus or Malassezia sp) or self antigens
(e.g. human thioredoxin).
•
(v) abnormal skin colonization by microbes: S aureus colonizes the skin in 90% of AD patients
(staphylococcal enterotoxins induce polyclonal T-cell and B-cell activation).
•
TH2 responses: (i) driven by TH2 lymphocytes; (ii) important cytokines: IL-3, IL-4, IL-5, IL-9, IL13; (iii) pathogenic mechanisms: IgE production, mast cell, basophil and eosinophil activation.
•
TH22 responses: (i) driven by TH22 lymphocytes; (ii) important cytokine: IL-22; (iii) pathogenic
mechanisms: keratinocyte proliferation, diffuse epidermal hyperplasia (acanthosis).
•
Filaggrin: important role in the integrity of skin barrier; expressed by keratinocytes; not
expressed by nasal, bronchial or esophageal epithelium; loss-of-function genetic mutations
occur in 30% of AD patients (however, 8% of healthy subjects also carry those mutations).
•
Desmoglein 1 deficiency → ↓ epidermal intercellular adhesion → severe dermatitis, multiple
allergies, metabolic wasting.
•
Tmem79 (MATT in humans) deficiency → abnormal lamellar granule secretory system in the
epidermis → altered stratum corneum formation → pathogenic factor in atopic dermatitis.
•
‘Futuristic’ therapy of AD: determine specific AD phenotypes using clinical, laboratory, histologic
and genetic biomarkers → individualize therapy.
“But knowledge puffs up while love builds up” 1 Corinthians 8:1
12. Juan Carlos Aldave Becerra, MD
Allergy and Clinical Immunology
Rebagliati Martins National Hospital, Lima-Peru
•
CODING-REGION ALTERATIONS IN BTK DO NOT UNIVERSALLY CAUSE X-LINKED
AGAMMAGLOBULINEMIA (Abbott JK, Ochs HD, Gelfand EW. J Allergy Clin Immunol 2013; 132:
1246-1248):
•
•
Authors show that variants in the BTK gene can be nonpathogenic.
•
•
X-linked agammaglobulinemia (XLA): mutations in BTK gene → block in B-cell maturation at
pre-B stage → ↓ circulating B cells (<2% of peripheral blood lymphocytes) → ↓ production of
immunoglobulins → recurrent infections.
Author’s commentaries: (i) measure B-cell numbers in every male patient with ↓ serum
immunoglobulin levels (even with mild infectious history); (ii) consider an alternative diagnosis
when B-cell numbers are ≥2% (even if there is a coding region variation in the BTK gene).
EOSINOPHILIC ASTHMA: INSIGHTS INTO THE EFFECTS OF REDUCING IL-5 RECEPTOR–
POSITIVE CELL LEVELS (Assa’ad AH, Rothenberg ME. J Allergy Clin Immunol 2013; 132: 10971098):
•
•
Eosinophil-depleting mAbs (anti-IL-5 [mepolizumab, reslizumab], anti-IL-5Rα [benralizumab,
which also depletes basophils]): therapeutic options in patients with eosinophilic diseases
(hypereosinophilic syndrome, eosinophilic esophagitis, eosinophilic asthma); no significant side
effects (eg. patients with HES who have received mepolizumab for 6 yrs).
•
•
IL-5: main cytokine that stimulates eosinophil production, migration and survival.
Compared to bone marrow and circulating eosinophils, the tissue eosinophil might be less
responsive to certain antieosinophil agents, including corticosteroids.
GLUCOCORTICOID-INDUCED OSTEOPOROSIS: AN UPDATE ON EFFECTS AND
MANAGEMENT (Buehring B, Viswanathan R, Binkley N, Busse W. J Allergy Clin Immunol 2013;
132: 1019-1030):
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•
•
Glucocorticoids (GC): cornerstone of management of allergic and autoimmune diseases.
Glucocorticoid-induced osteoporosis (GIO): (i) most common iatrogenic cause of osteoporosis
(corticosteroids affect osteoclasts, osteoblasts and osteocytes); (ii) risk factor for fragility
fractures; (iii) most frequent due to oral GC administration (>5 mg/d prednisone for >3 months)
(iv) may also occur with high-dose GC topical therapy; (v) effective detection and management
of GIO is encouraged (main recommendations: adequate intake of calcium and vit D,
pharmacologic osteoporosis therapy in high-risk patients).
OUTCOMES OF THE CHILDHOOD ASTHMA PREVENTION STUDY AT 11.5 YEARS (Toelle BG,
Garden FL, Ng KKW, Belousova EG, Almqvist C, Cowell CT, Tovey ER, Webb KL, Leeder SR,
Marks GB. J Allergy Clin Immunol 2013; 132: 1220-1222):
•
Effectiveness of environmental interventions (e.g. allergen avoidance, breast feeding, maternal
diet) for the primary prevention of asthma is controversial.
•
Authors report the outcomes of The Childhood Asthma Prevention Study at 11.5 yrs of patient
follow up → (i) HDM avoidance and omega-3 fatty acid supplementation for the first 5 yrs of life
in high-risk children did not ↓ the prevalence of atopy, asthma or other atopic disorders at age
11.5 yrs; (ii) identifying effective interventions to prevent asthma remains an elusive challenge.
PEARLS IN ALLERGY AND IMMUNOLOGY
November 2013
13. The purpose of this summary is exclusively educational, to provide practical updated knowledge for Allergy/Immunology Physicians. It does not
intend to replace the clinical criteria of the physician.
•
REGIONAL DIFFERENCES IN THE EXPRESSION OF INNATE HOST DEFENSE MOLECULES IN
SINONASAL MUCOSA (Seshadri S, Rosati M, Lin DC, Carter RG, Norton JE, Choi AW, Suh L, Kato
A, Chandra RK, Harris KE, Chu HW, Peters AT, Tan BK, Conley DB, Grammer LC, Kern RC,
Schleimer RP. J Allergy Clin Immunol 2013; 132: 1220-1222):
•
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Nasal mucosal epithelial cells and glands: (i) barrier against the entry of airborne substances
and pathogens; (ii) secrete mucous, which immobilize pathogens and other harmful substances;
(iii) produce dozens of antimicrobial peptides (e.g. defensins, cathelicidin, S100A7, SPLUNC1,
lactoferrin): deleterious effect against bacteria, fungi, virus and parasites.
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Abnormal expression of host defense molecules has been linked to many airway diseases.
•
Authors show that expression of antimicrobial peptides differed between the inferior region
(inferior turbinate [IT]) and the superior region (uncinate tissue [UT]) of the sinonasal mucosa in
healthy human subjects.
•
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Innate immune system: (i) barriers: physical (e.g. skin, mucosal epithelium, cilia), chemical (e.g.
gastric acid), biological (e.g. commensal bacteria); (ii) soluble molecules (e.g. antimicrobial
peptides, complement system); (iii) cells (e.g. neutrophils, macrophages, NK lymphocytes).
Causal hypothesis for these findings: (i) maxilloturbinal (IT) vs ethmoturbinal (UT) tissues have
different embryonic origins; (ii) IT vs UT may have different environmental exposures
(pathogens, microbiota, pollutants, allergens); (iii) UT is located at a point of drainage of various
sinuses, so it might need special defense mechanisms (e.g. SPLUNC1 has surfactant
properties and may promote mucociliary clearance).
RHINOVIRUS SPECIFIC IGE CAN BE DETECTED IN HUMAN SERA (Tam JS, Jackson WT,
Hunter D, Proud D, Grayson MH. J Allergy Clin Immunol 2013; 132: 1241-1243):
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HRV: (i) nonenveloped, single-stranded RNA virus (Picornaviridae family); (ii) >150 serotypes
with many more distinct strains that can infect humans; (iii) 3 genetic clades (A, B, C); (iv) HRV
infection is ubiquitous.
•
Authors show that human subjects can develop specific IgE against HRV after exposure →
important implication in the pathogenesis of asthma exacerbations.
•
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Respiratory viral infections (mainly by respiratory syncytial virus [RSV] or human rhinovirus
[HRV]): important pathogenic factor in asthma development and exacerbations.
Author’s commentaries: (i) specific IgE has also been shown against RSV or influenza virus; (ii)
whether antiviral-specific IgE is a purposeful or maladaptive immune response, it appears to
contribute to the exacerbation and perhaps development of atopic disease.
THE BIOLOGY OF THE GLUCOCORTICOID RECEPTOR: NEW SIGNALING MECHANISMS IN
HEALTH AND DISEASE (Oakley RH, Cidlowski JA. J Allergy Clin Immunol 2013; 132: 1033-1044):
•
Glucocorticoids (GCs): (i) stress hormones necessary for life; (ii) synthetic GCs are potent
antiinflammatory drugs (cornerstone of management of allergic and autoimmune diseases).
•
Mechanism of action of GCs: diffusion across the cell membrane → binding to the
glucocorticoid receptor α (GRα) in the cytoplasm → GRα liberates from chaperone proteins
(HSP90) → GRα enters the nucleus through nuclear import proteins (importin α) → GRα
“But knowledge puffs up while love builds up” 1 Corinthians 8:1
14. Juan Carlos Aldave Becerra, MD
Allergy and Clinical Immunology
Rebagliati Martins National Hospital, Lima-Peru
homodimerizes → GR complex binds to gene promoters and induces or represses the
transcription of thousands of genes (e.g. switches off many activated inflammatory genes
[cytokines, chemokines, adhesion molecules, etc.]).
•
•
Mechanisms of GC resistance: (i) ↑ phosphorylation of the GRα by kinases (p38MAPK, JNK1),
↓ activity of phosphatases (MKP-1, PP2A) → ↓ nuclear translocation; (ii) ↑ expression of GRβ,
which competes with activated GRα; (iii) ↑ proinflammatory transcription factors (AP-1, JNK);
(iv) oxidative stress → activation of PI3Kδ → ↓ expression of histone deacetylase 2 (HDAC2),
which normally switches off activated inflammatory genes.
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Strategies for managing GC resistance: (i) anti-inflammatory drugs: phosphodiesterase 4
inhibitors (e.g. oral roflumilast for COPD), p38MAPK inhibitors, NF-kB inhibitors, macrolides; (ii)
drugs that ↑ HDAC2 expression: theophylline, nortriptyline, PI3Kδ inhibitors; (iii) LABA: ↑ PP2A,
↓ GRα phosphorylation, ↑ GRα translocation to the nucleus; (iv) antioxidants: Nrf2 activators.
•
Many factors affect sensitivity and specificity to GCs: (i) GR isoform; (ii) GC type; (iii) GC
concentration; (iv) GC target genes; (v) target cell/tissue.
•
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GR: (i) there are many isoforms, with unique expression, gene-regulatory and functional
profiles; (ii) GR isoforms derive from a single gene by alternative splicing of the primary
transcript, alternative translation initiation of the mature mRNA, and posttranslational
modifications of the encoded protein → ↑ diversity of glucocorticoid responses both in healthy
and diseased tissues.
Dissociated or selective glucocorticoid receptor agonists (SEGRAs) (in research): (i) retain the
antiinflammatory effects of GCs; (ii) lose the adverse effects of GCs.
THE EDITORS’ CHOICE (Leung DYM, Szefler SJ. J Allergy Clin Immunol 2013; 132: 1056-1057):
•
•
Tiotropium bromide: add-on therapy for asthma control; (i) factors associated with a positive
response to tiotropium in uncontrolled asthmatic patients: higher cholinergic tone, positive
immediate response to albuterol, airway obstruction; (ii) factors not associated with a positive
response to tiotropium: ethnicity, sex, atopy, IgE level, sputum eosinophil count, FENO, asthma
duration, body mass index.
•
Long-acting β2-agonists → ↑ nuclear translocation of the activated glucocorticoid receptor in
sputum macrophages (equivalent to that seen with a 5-fold higher dose of ICS) → ↑
corticosteroid sensitivity in patients with COPD.
•
Tmem79 (MATT): novel skin barrier–related gene involved in the pathogenesis of atopic
dermatitis.
•
•
73% of patients with cow’s milk–mediated eosinophilic esophagitis (CMME) tolerated significant
amounts of baked milk products without recurrence of symptoms or esophageal inflammation
→ this finding could improve adherence to diet, QoL and nutrition in patients with CMME.
Futuristic approach in asthma/wheezing: use of clinical data and biomarkers to identify specific
asthma/wheezing phenotypes → give individualized therapy (e.g. leukotriene-induced asthma
→ give antileukotrienes).
THE LONG ROAD TO OPTIMAL MANAGEMENT FOR CHRONIC GRANULOMATOUS DISEASE
(Notarangelo LD. J Allergy Clin Immunol 2013; 132: 1164-1165):
PEARLS IN ALLERGY AND IMMUNOLOGY
November 2013
15. The purpose of this summary is exclusively educational, to provide practical updated knowledge for Allergy/Immunology Physicians. It does not
intend to replace the clinical criteria of the physician.
•
•
Forms of CGD: (i) X-linked CGD (the most frequent): mutations of the CYBB gene encoding for
the gp91phox subunit of the NADPH oxidase complex; (ii) autosomal recessive CGD: mutations
of the genes that encode for the p22phox, p47phox, p67phox, and p40phox subunits.
•
NADPH oxidase activity: (i) can be measured by the dihydrorhodamine test; (ii) might help to
predict outcomes in CGD patients.
•
Treatment of CGD: (i) curative treatment: HSCT (for which patients and when is still matter of
debate), gene therapy; (ii) supportive treatment to prevent infections: antibacterial and
antifungal prophylaxis, IFN-γ; (iii) supportive treatment for granulomas and inflammatory
manifestations: immunosuppressive agents (corticosteroids, azathioprine, anti-TNF-α,
thalidomide; significant side effects; ↑ infection risk).
•
Koker et al (J Allergy Clin Immunol 2013; 132: 1156-63): patients with p47phox deficiency had
more NADPH oxidase residual activity compared to patients with gp91phox, p22phox or
p67phox deficiency → clinical course in patients with p47phox deficiency was less severe.
•
Cole et al (J Allergy Clin Immunol 2013; 132: 1150-55): HSCT reduced the incidence of serious
complications but did not affect survival in patients with CGD at short term follow-up.
•
•
Chronic granulomatous disease (CGD): genetic defects of the phagocyte NADPH oxidase
complex → phagocyte dysfunction (impaired production of microbicidal ROS) → severe
bacterial and fungal infections, granuloma formation, inflammatory manifestations (e.g. colitis
[mimicking Crohn disease], interstitial pneumonitis, nodular pneumonia, neutrophilic dermatosis,
granulomatous hepatitis, cystitis) → high early mortality in the absence of treatment (disease
severity reflects the degree of residual [if any] NADPH oxidase activity).
Comparing outcomes of conservative versus curative treatment in CGD patients with similar
levels of oxidase activity is of outmost importance.
USE OF ONDANSETRON FOR FOOD PROTEIN–INDUCED ENTEROCOLITIS SYNDROME
(FPIES) (Holbrook T, Keet, CA, Frischmeyer-Guerrerio PA, Wood RA. J Allergy Clin Immunol 2013;
132: 1219-1220):
•
FPIES: (i) non-IgE-mediated allergy to food proteins (potentially severe); (ii) clinical history
(usually starts in the 1st yr of life): vomiting, diarrhea, dehydration, electrolyte disbalance,
hypotension, shock, acidemia, methemoglobinemia (2-6 hrs after eating the culprit food); (iii)
frequent culprits: cow’s milk, soy, grains; (iv) diagnosis: clinical history, oral food challenge; (v)
treatment: allergen avoidance; (vi) prognosis: FPIES typically resolves by 3-5 yrs of age
(medically supervised OFCs are usually performed to confirm FPIES resolution); (vii) breast-fed
infants with FPIES can typically continue lactating without maternal avoidance (FPIES is very
rare in exclusively breast-fed infants).
•
Ondansetron hydrochloride: (i) highly potent and selective serotonin 5-HT3 receptor antagonist
(peripheral and central receptors); (ii) approved to prevent and treat nausea/vomiting induced
by chemotherapy or radiation; (iii) low risk of adverse effects (be cautious in children with
underlying heart disease, as QT prolongation has been observed); (iv) used successfully offlabel in emergency room settings to control vomiting (such as in acute gastroenteritis).
•
Authors report the rapid efficacy of ondansetron in 5 children who had FPIES reactions during
oral food challenges.
“But knowledge puffs up while love builds up” 1 Corinthians 8:1
16. Juan Carlos Aldave Becerra, MD
Allergy and Clinical Immunology
Rebagliati Martins National Hospital, Lima-Peru
•
Author’s commentaries: (i) ondansetron may have great value in treating FPIES reactions; (ii)
the apparent efficacy of ondansetron raises questions as to whether inflammation is the central
mechanism underlying FPIES and whether corticosteroids truly have a role in FPIES treatment;
(iii) ondansetron should be routinely used in the treatment of FPIES reactions, both in the food
challenge setting and in the emergency room.
PEARLS IN ALLERGY AND IMMUNOLOGY
November 2013