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.
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.
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.
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.
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 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.
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 - 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.
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, 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.
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.
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.
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 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.
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 - 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.
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.
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.
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.
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
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.
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
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
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
FPIAP is a non-IgE mediated gastrointestinal food allergy that is the mildest form. It is characterized by the presence of blood and sometimes mucus in the stools of otherwise healthy infants. It affects infants under 6 months of age, with symptoms appearing between 2-8 weeks of life. The most common triggering foods are cow's milk protein in breastfed infants and soy, cow's milk protein, and extensively hydrolyzed formulas in formula-fed infants. The diagnosis is based on clinical history and resolution of symptoms with dietary elimination of trigger foods. Prognosis is excellent, with tolerance developing in most children by 1-3 years of age.
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.
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.
Pearls in Allergy and Immunology, November 2013Juan Aldave
- 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 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.
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
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.
1. The document summarizes various studies on prevention of allergy through modulation of the gut microbiota from early life.
2. Key areas of focus include the gut microbiota of pregnant women and its impact on the infant, early introduction of foods like peanuts and eggs to induce tolerance, use of probiotics and breastfeeding to influence the infant gut microbiota, and effects of a farm environment and dietary fibers on allergy risk.
3. Studies found that probiotics started prenatally and combined with breastfeeding were most effective in preventing eczema, and that early introduction of peanuts and eggs reduced the risk of developing an allergy to those foods.
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.
1) A study of 651 children with pollen-related allergic rhinitis found that component-resolved diagnosis identified a lack of IgE antibodies to major allergens in a significant percentage of patients with skin prick test reactivity, calling into question the appropriateness of immunotherapy for some patients.
2) Without component-resolved diagnosis, immunotherapy would have been prescribed inappropriately in 37% of cases based on skin prick test alone.
3) Component-resolved diagnosis led European and American allergists to change their immunotherapy prescription decisions in 42-48% of cases compared to skin prick testing alone.
What is new in general pediatrics, allergic and respiratory diseasesEnvicon Medical Srl
The document discusses several studies related to general pediatrics, allergic and respiratory diseases from 2017.
One study found that early-term deliveries between 37-38 weeks gestation were associated with increased risk of long-term respiratory morbidity compared to full-term deliveries between 39-40 weeks. Another study showed that preschoolers with bedtimes before 8pm had a lower risk of adolescent obesity than those with later bedtimes. A third study found that high school start times later than 8:30am were associated with improved attendance and graduation rates.
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.
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.
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.
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
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.
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
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
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
FPIAP is a non-IgE mediated gastrointestinal food allergy that is the mildest form. It is characterized by the presence of blood and sometimes mucus in the stools of otherwise healthy infants. It affects infants under 6 months of age, with symptoms appearing between 2-8 weeks of life. The most common triggering foods are cow's milk protein in breastfed infants and soy, cow's milk protein, and extensively hydrolyzed formulas in formula-fed infants. The diagnosis is based on clinical history and resolution of symptoms with dietary elimination of trigger foods. Prognosis is excellent, with tolerance developing in most children by 1-3 years of age.
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.
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.
Pearls in Allergy and Immunology, November 2013Juan Aldave
- 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 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.
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
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.
1. The document summarizes various studies on prevention of allergy through modulation of the gut microbiota from early life.
2. Key areas of focus include the gut microbiota of pregnant women and its impact on the infant, early introduction of foods like peanuts and eggs to induce tolerance, use of probiotics and breastfeeding to influence the infant gut microbiota, and effects of a farm environment and dietary fibers on allergy risk.
3. Studies found that probiotics started prenatally and combined with breastfeeding were most effective in preventing eczema, and that early introduction of peanuts and eggs reduced the risk of developing an allergy to those foods.
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.
1) A study of 651 children with pollen-related allergic rhinitis found that component-resolved diagnosis identified a lack of IgE antibodies to major allergens in a significant percentage of patients with skin prick test reactivity, calling into question the appropriateness of immunotherapy for some patients.
2) Without component-resolved diagnosis, immunotherapy would have been prescribed inappropriately in 37% of cases based on skin prick test alone.
3) Component-resolved diagnosis led European and American allergists to change their immunotherapy prescription decisions in 42-48% of cases compared to skin prick testing alone.
What is new in general pediatrics, allergic and respiratory diseasesEnvicon Medical Srl
The document discusses several studies related to general pediatrics, allergic and respiratory diseases from 2017.
One study found that early-term deliveries between 37-38 weeks gestation were associated with increased risk of long-term respiratory morbidity compared to full-term deliveries between 39-40 weeks. Another study showed that preschoolers with bedtimes before 8pm had a lower risk of adolescent obesity than those with later bedtimes. A third study found that high school start times later than 8:30am were associated with improved attendance and graduation rates.
This document reviews the association between atopic conditions like asthma, allergic rhinitis, and atopic dermatitis with an increased risk of respiratory and non-respiratory tract infections. It discusses several potential mechanisms for this association, including dysfunction in innate immunity, humoral immunity, and cell-mediated immunity in atopic individuals. Specific examples are provided of impaired responses to pathogens like bacteria and viruses in those with asthma or allergies. The role of corticosteroid use and asthma severity/control in modifying infection risk is also examined.
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.
Immunological Aspects of Myasthenia Gravis Ade Wijaya
MG is an antibody-mediated neuromuscular junction disease caused by IgG antibodies against acetylcholine receptors or the muscle-specific kinase in some cases. The thymus often exhibits structural changes like tumors or follicular hyperplasia and plays an important role in the pathogenesis by impairing regulatory T cells and conventional T cells, creating a pro-inflammatory environment. Understanding the immunological mechanisms involved helps manage patients.
This document discusses ascariasis, a common helminth infection caused by the roundworm Ascaris lumbricoides. It infects over 25% of the world's population, predominantly children. Symptoms can include growth retardation, pneumonia, and intestinal obstruction. The life cycle and immunosuppressive effects of ascariasis are described, including its role in modulating the immune system and suppressing inflammatory responses through molecules like PAS-1. The hygiene hypothesis, which proposes that lack of early childhood exposure to pathogens like helminths may increase risk for allergic diseases, is also discussed.
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.
Efficacy and safety of immunomodulators in pediatric age - Slideset by Profes...WAidid
«The first cause of recurrent infections in children is... childhood itself.» (J. Gary Wheeler)
Is it possibe to treat and prevent recurrent respiratory infections (RTIs) in pediatric age? Some studies have shown that immunostimulants/immunomodulators can reduce and prevent RTIs in children.
To learn more please visit www.waidid.org
The document discusses food immunotherapy for treating food allergies. It provides definitions and outlines immune mechanisms and efficacy evidence from studies on peanut, cow's milk, egg, and wheat oral immunotherapy (OIT). Peanut OIT studies showed 67-78% of children achieved desensitization and 21-46% achieved sustained unresponsiveness. Cow's milk and egg OIT also demonstrated desensitization in 50-75% of children. Wheat OIT studies found 52-69% achieved desensitization. OIT was effective at increasing tolerance but also increased rates of adverse events during treatment.
Initiate infusion at a rate of 100 mg/hr, and increase by 100 mg/hr increments every 30 minutes to a maximum of 400 mg/hr as tolerated.
- In the absence of infusion reactions, a more rapid infusion can be administered within 6 hours.
- Premedicate with acetaminophen and an antihistamine approximately 30-60 minutes before each infusion.
- For patients with a history of infusion reactions, premedicate with corticosteroids (methylprednisolone or equivalent).
Specific drug - Rituximab
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.
The document discusses immune responses associated with pathology and allergies. It references three sources that cover non-immune mediators associated with hormonal mechanisms, the perioperative approach for allergic patients, and anesthesia, surgery, and life-threatening allergic reactions including management, outcomes, and recommendations. The bibliography lists the three sources cited in the document.
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 summarizes research on vaccination in children with chronic diseases. It discusses issues with influenza and pneumococcal vaccinations in high-risk groups. It reviews studies examining the immunogenicity, safety and efficacy of influenza and pneumococcal vaccines in various chronic conditions like asthma, cancer, and immunosuppression. It also discusses gaps in knowledge around the impact of influenza in different at-risk groups and the need for more data on vaccine immunogenicity, safety and efficacy in each high-risk population. The document emphasizes the importance of recommending influenza vaccination for children with chronic diseases and implementing strategies to increase vaccination coverage.
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.
Clinic ^%[+27633867063*Abortion Pills For Sale In Tembisa Central19various
Clinic ^%[+27633867063*Abortion Pills For Sale In Tembisa Central Clinic ^%[+27633867063*Abortion Pills For Sale In Tembisa CentralClinic ^%[+27633867063*Abortion Pills For Sale In Tembisa CentralClinic ^%[+27633867063*Abortion Pills For Sale In Tembisa CentralClinic ^%[+27633867063*Abortion Pills For Sale In Tembisa Central
5-hydroxytryptamine or 5-HT or Serotonin is a neurotransmitter that serves a range of roles in the human body. It is sometimes referred to as the happy chemical since it promotes overall well-being and happiness.
It is mostly found in the brain, intestines, and blood platelets.
5-HT is utilised to transport messages between nerve cells, is known to be involved in smooth muscle contraction, and adds to overall well-being and pleasure, among other benefits. 5-HT regulates the body's sleep-wake cycles and internal clock by acting as a precursor to melatonin.
It is hypothesised to regulate hunger, emotions, motor, cognitive, and autonomic processes.
Kosmoderma Academy, a leading institution in the field of dermatology and aesthetics, offers comprehensive courses in cosmetology and trichology. Our specialized courses on PRP (Hair), DR+Growth Factor, GFC, and Qr678 are designed to equip practitioners with advanced skills and knowledge to excel in hair restoration and growth treatments.
1. February 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
February 2013 – content:
• A MULTICENTER, RANDOMIZED, CONTROLLED TRIAL TESTING THE EFFECTS OF ACUPUNCTURE
ON ALLERGIC RHINITIS (AR) (Choi S-M, Park J-E, Li S-S, Jung H, Zi M, Kim T-H, Jung S, Kim A, Shin M,
Sul J-U, Hong Z, Jiping Z, Lee S, Liyun H, Kang K, Baoyan L. Allergy 2013; 68: 365–374).
• BLOOD EOSINOPHIL COUNTS RARELY REFLECT AIRWAY EOSINOPHILIA IN CHILDREN WITH
SEVERE ASTHMA (Ullmann N, Bossley CJ, Fleming L, Silvestri M, Bush A, Saglani S. Allergy 2013; 68: 402–
406).
• EOSINOPHIL-DERIVED CYTOKINES IN HEALTH AND DISEASE: UNRAVELING NOVEL MECHANISMS
OF SELECTIVE SECRETION (Melo RCN, Liu L, Xenakis JJ, Spencer LA. Allergy 2013; 68: 274–284).
• EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS (EGPA, CHURG–STRAUSS): STATE OF THE
ART (Vaglio A, Buzio C, Zwerina J. Allergy 2013; 68: 261–273).
• UNEXPLAINED RECURRENT FEVER: WHEN IS AUTOINFLAMMATION THE EXPLANATION? (Kallinich T,
Gattorno M, Grattan CE, de Koning HD, Traidl-Hoffmann C, Feist E, Krause K, Lipsker D, Navarini AA, Maurer
M, Lachmann HJ, Simon A. Allergy 2013; 68: 285–296).
• A CASE OF DRESS SYNDROME INDUCED BY THE ANTITUBERCULOSIS DRUGS, PROTHIONAMIDE,
AND PARA-AMINOSALYCILIC ACID (Joo-Hee Kim, Seung Hun Jang, Dong Hoon Kim, Sunghoon Park,
Dong-Gyu Kim, Ki-Suck Jung. Ann Allergy Asthma Immunol 2013; 110: 118–119).
• ADVERSE REACTIONS DURING DRUG CHALLENGES: A SINGLE US INSTITUTION’S EXPERIENCE (Kao
L, Rajan J, Roy L, Kavosh E, Khan DA. Ann Allergy Asthma Immunol 2013; 110: 86–91).
• ASTHMA MEDICATION ADHERENCE: THE ROLE OF GOD AND OTHER HEALTH LOCUS OF CONTROL
FACTORS (Ahmedani BK, Peterson EL, Wells KE, Rand CS, Williams LK. Ann Allergy Asthma Immunol 2013;
110: 75–79).
• CHARACTERIZATION OF ASPIRIN ALLERGIES IN PATIENTS WITH CORONARY ARTERY DISEASE
(Feng CH, White AA, Stevenson DD. Ann Allergy Asthma Immunol 2013; 110: 92–95).
• EFFECT OF MITE ALLERGEN IMMUNOTHERAPY ON THE ALTERED PHENOTYPE OF DENDRITIC
CELLS IN ALLERGIC ASTHMATIC CHILDREN (Chuang-Ming Wang, Jing-Jing Chuang. Ann Allergy Asthma
Immunol 2013; 110: 107-112).
• LONG-TERM EFFICACY OF FIXED-DOSE OMALIZUMAB FOR PATIENTS WITH SEVERE CHRONIC
SPONTANEOUS URTICARIA (Song CH, Stern S, Giruparajah M, Berlin N, Sussman GL. Ann Allergy Asthma
Immunol 2013; 110: 113-117).
• MANAGEMENT OF HEREDITARY ANGIOEDEMA (HAE) IN 2012: SCIENTIFIC AND
PHARMACOECONOMIC PERSPECTIVES (Tilles SA, Borish L, Cohen JP. Ann Allergy Asthma Immunol
2013; 110: 70-74).
• MANNOSE-BINDING LECTIN DEFICIENCY IN A PATIENT WITH MULTIPLE OPPORTUNISTIC
INFECTIONS, STRONGYLOIDIASIS, AND SPINDLE CELL TUMOR (Parikh P, Kooragayalu S, Jariwala S.
Ann Allergy Asthma Immunol 2013; 110: 120-121).
• MOSQUITO ALLERGY (Crisp HC, Johnson KS. Ann Allergy Asthma Immunol 2013; 110: 65-69).
• PERSISTENT PAPILLOMA AND POLYOMA VIRUS INFECTION IN COMMON VARIABLE
IMMUNODEFICIENCY (CVID) WITH PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (Nabavi
M, Arshi S, Fallahpour M, Esmaeilzadeh H. Ann Allergy Asthma Immunol 2013; 110: 119-120).
• SHOULD EXHALED NITRIC OXIDE BE PART OF ROUTINE ASTHMA MANAGEMENT? (Jain, MD Peter
Boggs, MD Myron Zitt, MD. Ann Allergy Asthma Immunol 2013; 110: 129-130).
• SUCCESS WITH IMMUNOMODULATORY THERAPIES IN THE TREATMENT OF RECALCITRANT
CHRONIC URTICARIA (CU) (Pongonis RM, Fahrenholz JM. Ann Allergy Asthma Immunol 2013; 110: 123-
124).
PEARLS IN ALLERGY AND IMMUNOLOGY February 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.
• WHEAT-DEPENDENT EXERCISE-INDUCED ANAPHYLAXIS (WDEIA) IN ELDERLY PATIENTS (Pérez-
Rangel I, Gonzalo-Garijo MA, Pérez-Calderón R, Zambonino MA, Corrales-Vargas SI. Ann Allergy Asthma
Immunol 2013; 110: 121-122).
• ABERRANT GLYCOSYLATION OF IGA IN WISKOTT-ALDRICH SYNDROME (WAS) AND X-LINKED
THROMBOCYTOPENIA (XLT) (Shimizu M, Kanegane H, Wada T, Motoyoshi Y, Morio T, Candotti F, Yachie
A. J Allergy Clin Immunol 2013; 131: 587-590).
• ANTIGEN-SPECIFIC T-CELL RESPONSES IN PATIENTS WITH NON–IGE-MEDIATED
GASTROINTESTINAL FOOD ALLERGY ARE PREDOMINANTLY SKEWED TO TH2 (Morita H, Nomura I,
Orihara K, Yoshida K, Akasawa A, Tachimoto H, Ohtsuka Y, Namai Y, Futamura M, Shoda T, Matsuda A,
Kamemura N, Kido H, Takahashi T, Ohya Y, Saito H, Matsumoto K. J Allergy Clin Immunol 2013; 131: 590-
592).
• ATOPIC DERMATITIS: A PRACTICE PARAMETER UPDATE 2012 (Schneider L, Tilles S, Lio P, Boguniewicz
M, Beck L, LeBovidge J, Novak N. J Allergy Clin Immunol 2013; 131: 295-299).
• CLASSIFICATION OF PRIMARY IMMUNODEFICIENCIES: NEED FOR A REVISED APPROACH? (Maggina
P, Gennery AR. J Allergy Clin Immunol 2013; 131: 292-294).
• COMBINED DOCK8 AND CLEC7A MUTATIONS CAUSING IMMUNODEFICIENCY IN 3 BROTHERS WITH
DIARRHEA, ECZEMA, AND INFECTIONS (Dinwiddie DL, Kingsmore SF, Caracciolo S, Rossi G, Moratto D,
Mazza C, Sabelli C, Bacchetta R, Passerini L, Magri C, Bell CJ, Miller NA, Hateley SL, Saunders CJ, Zhang L,
Schroth GP, Barlati S, Badolato R. J Allergy Clin Immunol 2013; 131: 594-597).
• DISSEMINATED MYCOBACTERIUM GENAVENSE INFECTION AFTER IMMUNOSUPPRESSIVE THERAPY
SHOWS UNDERLYING NEW COMPOSITE HETEROZYGOUS MUTATIONS OF β1 SUBUNIT OF IL-12
RECEPTOR GENE (Tassone L, Carvalho ACC, Calabresi A, Tortoli E, Apostoli A, Scomodon O, Spina C,
Vairo D, Villanacci V, Matteelli A, Badolato R. J Allergy Clin Immunol 2013; 131: 607-610).
• FORKHEAD BOX PROTEIN 3 (FOXP3) HYPERMETHYLATION IS ASSOCIATED WITH DIESEL EXHAUST
EXPOSURE AND RISK FOR CHILDHOOD ASTHMA (Brunst KJ, Leung YK, Ryan PH, Khurana Hershey GK,
Levin L, Ji H, LeMasters GK, Ho SM. J Allergy Clin Immunol 2013; 131: 592-594).
• GENETIC VARIATION IN THE TOLL-LIKE RECEPTOR SIGNALING PATHWAY IS ASSOCIATED WITH
CHILDHOOD ASTHMA (Pandey RC, Michel S, Tesse R, Binia A, Schedel M, Liang L, Klopp N, Franke A, von
Berg A, Bufe A, Rietschel E, Heinzmann A, Laub O, Simma B, Frischer T, Genuneit J, Illig T, Kabesch M. J
Allergy Clin Immunol 2013; 131: 602-605).
• PRIMARY IMMUNODEFICIENCIES: A RAPIDLY EVOLVING STORY (Parvaneh N, Casanova JL,
Notarangelo LD, Conley ME. J Allergy Clin Immunol 2013; 131: 314-323).
• PROPHYLACTIC THERAPY IN CHILDREN WITH HEREDITARY ANGIOEDEMA (HAE) (Farkas H, Csuka D,
Zotter Z, Varga L, Füst G. J Allergy Clin Immunol 2013; 131: 579-582).
• TGF-β1 POLYMORPHISMS AND ASTHMA SEVERITY, AIRWAY INFLAMMATION, AND REMODELING
(Ierodiakonou D, Postma DS, Koppelman GH, Gerritsen J, ten Hacken NHT, Timens W, Marike Boezen H,
Vonk JM. J Allergy Clin Immunol 2013; 131: 582-585).
• TICK-BORNE ENCEPHALITIS VIRUS VACCINE AS ADDITIONAL ALTERNATIVE NEOANTIGEN FOR THE
CLINICAL IMMUNOLOGIST’S TOOLBOX (Seidel MG, Planitzer CB, Kreil TR, Förster-Waldl E. J Allergy Clin
Immunol 2013; 131: 617).
• ζ CHAIN–ASSOCIATED PROTEIN OF 70 KDA (ZAP70) DEFICIENCY IN HUMAN SUBJECTS IS
ASSOCIATED WITH ABNORMALITIES OF THYMIC STROMAL CELLS (Poliani PL, Fontana E, Roifman CM,
Notarangelo LD. J Allergy Clin Immunol 2013; 131: 597-600).
• A PROPOSED EXPLANATION FOR INCREASED RISK OF ACTIVE TUBERCULOSIS IN CHILDREN WITH
ALLERGIC DISEASE (Eisenhut M. Pediatr Allergy Immunol 2013: 24: 98).
• C1-INH CONCENTRATE FOR TREATMENT OF ACUTE HEREDITARY ANGIOEDEMA: A PEDIATRIC
COHORT FROM THE I.M.P.A.C.T. STUDIES (Schneider L, Hurewitz D, Wasserman R, Obtulowicz K, Machnig
T, Moldovan D, Reshef A, Craig TJ. Pediatr Allergy Immunol 2013: 24: 54–60).
• DESENSITIZATION TO ANTIBIOTICS IN CHILDREN (Cernadas JR. Pediatr Allergy Immunol 2013: 24: 3–9).
PEARLS IN ALLERGY AND IMMUNOLOGY February 2013
4. Juan Carlos Aldave Becerra, MD
Allergy and Clinical Immunology
Rebagliati Martins National Hospital, Lima-Peru
• ORAL FOOD DESENSITIZATION IN CHILDREN WITH IGE-MEDIATED HEN’S EGG ALLERGY: A NEW
PROTOCOL WITH RAW HEN’S EGG (Meglio P, Giampietro PG, Carello R, Gabriele I, Avitabile S, Galli E.
Pediatr Allergy Immunol 2013: 24: 75–83).
• POSITIVE NICKEL PATCH TESTS IN INFANTS ARE OF LOW CLINICAL RELEVANCE AND RARELY
REPRODUCIBLE (Mortz CG, Kjaer HF, Eller E, Osterballe M, Norberg LA, Høst A, Bindslev-Jensen C,
Andersen KE. Pediatr Allergy Immunol 2013: 24: 84–87).
• SAFETY OF MOMETASONE FUROATE NASAL SPRAY IN THE TREATMENT OF NASAL POLYPS IN
CHILDREN (Chur V, Small CB, Stryszak P, Teper A. Pediatr Allergy Immunol 2013: 24: 33–38).
• SPECIFIC ORAL TOLERANCE INDUCTION WITH RAW HEN’S EGG IN CHILDREN WITH VERY SEVERE
EGG ALLERGY: A RANDOMIZED CONTROLLED TRIAL (Dello Iacono I, Tripodi S, Calvani M, Panetta V,
Verga MC, Miceli Sopo S. Pediatr Allergy Immunol 2013: 24: 66–74).
• WHEN SHOULD ADRENALINE BE GIVEN AND BY WHOM? (Dreborg S. Pediatr Allergy Immunol 2013: 24:
97–98).
PEARLS IN ALLERGY AND IMMUNOLOGY February 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.
ALLERGY:
• A MULTICENTER, RANDOMIZED, CONTROLLED TRIAL TESTING THE EFFECTS OF
ACUPUNCTURE ON ALLERGIC RHINITIS (AR) (Choi S-M, Park J-E, Li S-S, Jung H, Zi M, Kim T-
H, Jung S, Kim A, Shin M, Sul J-U, Hong Z, Jiping Z, Lee S, Liyun H, Kang K, Baoyan L. Allergy
2013; 68: 365–374):
• Authors report 97 and 94 patients (>18 yr old) with moderate-severe persistent AR who
received active or sham acupuncture, respectively (3 times/wk for 4 wks) → both active and
sham acupuncture ↓ significantly AR symptoms; effect was greater with active acupuncture.
• Acupuncture: needles are inserted at specific points in the body, and manipulated or electrically
stimulated; ↓ symptoms of several diseases, including osteoarthritis, vomiting and itch.
• BLOOD EOSINOPHIL COUNTS RARELY REFLECT AIRWAY EOSINOPHILIA IN CHILDREN
WITH SEVERE ASTHMA (Ullmann N, Bossley CJ, Fleming L, Silvestri M, Bush A, Saglani S. Allergy
2013; 68: 402–406):
• Authors report 88 children (6–17 yr old) with severe therapy-resistant asthma → blood
eosinophilia suggested high likelihood of airway eosinophilia; however, normal blood eosinophil
levels did not exclude airway eosinophilic inflammation.
• Blood eosinophil counts rarely reflect airway inflammation in severe asthmatic children.
• EOSINOPHIL-DERIVED CYTOKINES IN HEALTH AND DISEASE: UNRAVELING NOVEL
MECHANISMS OF SELECTIVE SECRETION (Melo RCN, Liu L, Xenakis JJ, Spencer LA. Allergy
2013; 68: 274–284):
• Eosinophil functions: cytotoxicity, repair, remodeling, angiogenesis, immunomodulation.
• Eosinophils can store cytokines in cytoplasmic granules → immediate availability.
• Eosinophils do not only express Th2 cytokines, but also Th1 and regulatory cytokines.
• Secretion of preformed intracellular granules occur in 4 ways: (i) classic exocytosis: granules
fuse with cell membrane → total release of single granule’s contents; (ii) compound exocytosis:
≥2 granules fuse prior to fusion with cell membrane → simultaneous release of multiple granule
contents; (iii) piecemeal degranulation (PMD): cytokines are selectively depleted from granules
and transported within secretory vesicles to the cell membrane for release; (iv) cytolysis: intact
granules are liberated through a ruptured cell membrane.
• Most commonly observed mechanisms of eosinophil degranulation in human diseases in vivo:
PMD and cytolysis.
• Receptor-mediated trafficking of cognate cytokines: exogenous stimulation of the eosinophil →
specific cytokine receptor chains mobilize to intracellular granules → receptors sequester
granule-derived cognate cytokines → the conjugate cytokine-receptor is packaged into
secretory vesicles → vesicles are transported to the cell membrane for secretion.
• EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS (EGPA, CHURG–STRAUSS): STATE
OF THE ART (Vaglio A, Buzio C, Zwerina J. Allergy 2013; 68: 261–273):
PEARLS IN ALLERGY AND IMMUNOLOGY February 2013
6. Juan Carlos Aldave Becerra, MD
Allergy and Clinical Immunology
Rebagliati Martins National Hospital, Lima-Peru
• EGPA: usual onset: 40–60 yr old; pediatric cases have been reported.
• Pathogenesis: not well defined; association with HLA-DRB4; possibly triggered by infections,
allergens or drugs; Th2 responses are prominent; Th1 and Th17 responses are not negligible;
increased production, recruitment, activation and survival of eosinophils; humoral immunity is
dysregulated (prominent IgG4 and IgE responses).
• 3 phases, which partially overlap: 1) prodromic, allergic phase: asthma (95-100% of patients)
and rhinosinusitis; 2) eosinophilic phase: marked peripheral eosinophilia (>1,500/μL), organ
involvement (lungs, heart, GI tract); 3) vasculitic phase: systemic small-vessel vasculitis,
constitutional symptoms, peripheral neuropathy, renal damage, skin lesions, frequent
paradoxical improvement of asthma.
• Histology: eosinophilia, necrotizing vasculitis, eosinophil-rich granulomatous inflammation.
• Laboratory: marked eosinophilia; ↑ ESR, CRP, IgE and IgG4; ANCA are positive in ~40% of
patients (usually p-ANCA, anti-MPO), associated with vasculitis; increased eotaxin-3.
• Typical case of EGPA: Patient with adult-onset asthma and rhino-sinusitis, who develops
marked eosinophilia and lung infiltrates (peripheral, patchy and migratory).
• Treatment: glucocorticoids; immunosuppressants (e.g., cyclophosphamide, azathioprine,
methotrexate); new therapeutic options; mepolizumab (anti-IL5 mAb), rituximab (B-cell-
depleting agent).
• UNEXPLAINED RECURRENT FEVER: WHEN IS AUTOINFLAMMATION THE EXPLANATION?
(Kallinich T, Gattorno M, Grattan CE, de Koning HD, Traidl-Hoffmann C, Feist E, Krause K, Lipsker
D, Navarini AA, Maurer M, Lachmann HJ, Simon A. Allergy 2013; 68: 285–296):
• Differential diagnosis of recurrent fever: infections, neoplasms, autoimmune diseases,
autoinflammatory diseases, drugs, factitious, benign hyperthermia, central fever.
• Key questions to a patient with recurrent fever: 1) At what age did symptoms first appear; 2)
What is the duration of the individual fever episodes; 3) What is the time interval between
episodes (duration, variable or fixed intervals); 4) What other symptoms are associated with the
fever episodes; 5) What can trigger or alleviate a fever episode; 6) How have symptoms
developed over time; 7) Which treatments have been used and what was the response; 8) Is
there a family history; 9) Does the patient originate from a certain ethnicity?
• Authors present beautiful tables and figures to describe and differentiate autoinflammatory
syndromes.
PEARLS IN ALLERGY AND IMMUNOLOGY February 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.
ANNALS OF ALLERGY, ASTHMA & IMMUNOLOGY:
• A CASE OF DRESS SYNDROME INDUCED BY THE ANTITUBERCULOSIS DRUGS,
PROTHIONAMIDE, AND PARA-AMINOSALYCILIC ACID (Joo-Hee Kim, Seung Hun Jang, Dong
Hoon Kim, Sunghoon Park, Dong-Gyu Kim, Ki-Suck Jung. Ann Allergy Asthma Immunol 2013; 110:
118–119):
• DRESS (drug reaction with eosinophilia and systemic symptoms): rash, fever,
lymphadenopathy, eosinophilia, hepatitis; typically develops 2-8 weeks after drug initiation;
common culprit drugs: phenobarbital, carbamazepine, phenytoin, lamotrigine, sulfonamides;
diagnosis: drug challenge is the gold standard but it has high risk; patch tests, intradermal tests
and lymphocyte transformation tests may be useful.
• Authors report a 33-year-old man with DRESS caused by the second-line antituberculosis drugs
prothionamide and para-aminosalycilid acid. Diagnosis was confirmed by drug challenges.
• Severe reactions to antituberculosis drugs are a great trouble, especially in patients with
multidrug-resistant infections, because: 1) patients require prompt therapy; 2) patients need a
combination of several drugs; 3) therapy lasts months to years; 3) in some cases it is difficult to
find alternative drug regimens; 4) diagnostic tests are not standardized.
• ADVERSE REACTIONS DURING DRUG CHALLENGES: A SINGLE US INSTITUTION’S
EXPERIENCE (Kao L, Rajan J, Roy L, Kavosh E, Khan DA. Ann Allergy Asthma Immunol 2013; 110:
86–91):
• Drug challenge: gold standard test to diagnose or exclude drug hypersensitivity. Graded
challenge is performed when drug allergy is unlikely. Benefits: prevents false labeling of
“allergic” patients, eliminates need for drug desensitization, gives confidence to the patient.
• Many individuals report subjective symptoms after drug intake, which do not suggest a true
allergic reaction. Placebo-controlled drug challenge is performed when there is a high suspicion
of a nocebo effect (adverse reaction to placebo).
• Authors report 114 “allergic” patients who underwent 123 drug challenges (to the suspected
drug or a different drug within the same class) → only 1 patient apparently had a positive
reaction (delayed rash reported by phone call, it was not verified); 20 patients reported
subjective symptoms (risk factors: female gender, higher number of previous reactions,
previous subjective reactions).
• Low-risk drug challenges: (1) patients with negative penicillin skin test results challenged with a
penicillin; 2) penicillin allergic patients challenged with a cephalosporin or a carbapenem; (3)
challenges with local anesthetics.
• High-risk drug challenge: patients with aspirin-exacerbated respiratory disease (AERD) who
undergo aspirin challenge.
• ASTHMA MEDICATION ADHERENCE: THE ROLE OF GOD AND OTHER HEALTH LOCUS OF
CONTROL FACTORS (Ahmedani BK, Peterson EL, Wells KE, Rand CS, Williams LK. Ann Allergy
Asthma Immunol 2013; 110: 75–79):
PEARLS IN ALLERGY AND IMMUNOLOGY February 2013
8. Juan Carlos Aldave Becerra, MD
Allergy and Clinical Immunology
Rebagliati Martins National Hospital, Lima-Peru
• Adherence to therapy is low among patients with chronic diseases, such as asthma. Reasons:
patient issues (eg, low confidence); physician issues (eg, prescribing complex medication
regimens); administrative or financing issues (eg, high costs, limited access to appointments).
• Authors report 1,025 patients (5-56 years old) with asthma receiving ICS; patients were
considered adherent if ICS use was >80% of prescribed → adherence was low (36%); patients
who believed that God determined asthma control were less likely to be adherent.
• Health locus of control: individual’s belief about whom or what determines health (doctors,
personal behaviour, chance, God, etc.).
• CHARACTERIZATION OF ASPIRIN ALLERGIES IN PATIENTS WITH CORONARY ARTERY
DISEASE (Feng CH, White AA, Stevenson DD. Ann Allergy Asthma Immunol 2013; 110: 92–95):
• Hypersensitivity to aspirin: 1) respiratory sensitivity (asthma and/or rhinitis), 2) cutaneous
sensitivity (urticaria and/or angioedema), 3) anaphylaxis (very rare).
• Authors report 9,565 patients with coronary artery disease (CAD) → 142 patients (1.5%) had a
history of adverse reactions to aspirin; 30 patients (0.3%) had cutaneous and/or respiratory
reactions, the other patients had mostly gastrointestinal intolerance or bleeding; 34 patients
were receiving daily cardiovascular prophylaxis with aspirin; of 108 patients not receiving
aspirin, 25 were prescribed clopidogrel.
• Aspirin desensitization (elimination of pharmacologic and immunologic reactions by exposing a
patient to increasing doses of aspirin) was seriously underused in the study population.
• Since 1988, 87 aspirin desensitizations have been reported. Aspirin desensitization can be
performed in the emergency or in the outpatient setting.
• EFFECT OF MITE ALLERGEN IMMUNOTHERAPY ON THE ALTERED PHENOTYPE OF
DENDRITIC CELLS IN ALLERGIC ASTHMATIC CHILDREN (Chuang-Ming Wang, Jing-Jing
Chuang. Ann Allergy Asthma Immunol 2013; 110: 107-112):
• Effect of mite immunotherapy in dendritic cells of allergic asthmatic children: ↓ expression of
CD86 and HLA-DR; ↑ expression of TLR4.
• CD86, HLA-DR and TLR4 expression may be useful parameters for monitoring SIT efficacy.
• TLR4 agonists might overcome decreased TLR4 expression in allergic patients, with the
potential of improving SIT effects.
• LONG-TERM EFFICACY OF FIXED-DOSE OMALIZUMAB FOR PATIENTS WITH SEVERE
CHRONIC SPONTANEOUS URTICARIA (Song CH, Stern S, Giruparajah M, Berlin N, Sussman GL.
Ann Allergy Asthma Immunol 2013; 110: 113-117):
• Many patients with chronic spontaneous urticaria (CSU) do not improve with conventional
therapy, such as antihistamines or leukotriene antagonists.
• Authors report 16 patients with severe CSU who received omalizumab (150 mg every 2-4
weeks) between 2010 and 2011 → 10 patients (63%) had remission after the first injection; 4
patients (25%) required 2-6 treatments to achieve remission; 2 patients (12%) discontinued
treatment after 2 injections; of the 14 patients who initially benefited, 4 remain asymptomatic >9
PEARLS IN ALLERGY AND IMMUNOLOGY February 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.
months after their last injection, 7 patients continue in remission with maintenance omalizumab,
3 patients became refractory and discontinued treatment.
• Omalizumab was an effective treatment for inducing and maintaining long-term remission for
patients with severe CSU. Larger randomized trials are necessary to confirm these findings.
• MANAGEMENT OF HEREDITARY ANGIOEDEMA (HAE) IN 2012: SCIENTIFIC AND
PHARMACOECONOMIC PERSPECTIVES (Tilles SA, Borish L, Cohen JP. Ann Allergy Asthma
Immunol 2013; 110: 70-74):
• Drugs to prevent HAE attacks: 1) Attenuated androgens: low price; considerable dose-
dependent side effects; contraindicated in children, pregnancy and breastfeeding. 2) C1INH
replacement therapy (Cinryze, Viropharma): good safety profile; very expensive (highest annual
cost of any drug in the US); reduce 50% of attacks. 3) Tranexamic acid.
• Drugs to treat HAE attacks: 1) C1INH (Berinert, CSL Behring); 2) ecallantide (Kalbitor, Dyax):
inhibitor of kallikrein; 3) icatibant (Firazyr, Shire): bradykinin receptor antagonist. For the 3
agents, many patients improve in <30 minutes, 75% of patients improve in <4 hours, complete
alleviation is often achieved in 8-12 hours; none of the therapies completely control symptoms
in every patient. Good safety profile for the 3 agents (3% risk of anaphylaxis with ecallantide).
• 1983: the Orphan Drug Act (ODA) was declared to stimulate development of drugs for diseases
that affect <200,000 individuals (7-year market exclusivity, development tax credits, less
rigorous FDA approval process). In the decade before 1983 only 34 orphan drugs went on the
market; between 1983 and 2009 FDA approved 275 orphan drugs for 337 orphan indications.
• HAE affects approximately 6,000 individuals in the US (prevalence: 1/50,000) → all of the
recently approved HAE treatments were developed under the auspices of the ODA program.
• MANNOSE-BINDING LECTIN DEFICIENCY IN A PATIENT WITH MULTIPLE OPPORTUNISTIC
INFECTIONS, STRONGYLOIDIASIS, AND SPINDLE CELL TUMOR (Parikh P, Kooragayalu S,
Jariwala S. Ann Allergy Asthma Immunol 2013; 110: 120-121):
• Mannose-binding lectin (MBL) activates complement by the lectin pathway, facilitating pathogen
phagocytosis. It may also have an anti-tumorigenic role.
• Mutations in MBL2 gene → low levels of MBL → susceptibility to diverse infections (bacterial,
mycobacterial, viral, protozoal and fungal) and malignancies.
• Authors report a 66-year-old man with a history of spindle cell tumor, pulmonary Mycobacterium
avium infection, nasal aspergillus mycetoma and suspected strongyloidasis. Immunologic
evaluation demonstrated an undetectable MBL level of <0.5 ng/mL (normal >7.8 ng/mL).
• Infections by Mycobacterium avium and Aspergillus suggest a possible role of MBL in
augmenting adaptive cellular immune response.
• Always suspect MBL deficiency in patients with recurrent or atypical infections in whom other
studies of the immune system are normal.
• MOSQUITO ALLERGY (Crisp HC, Johnson KS. Ann Allergy Asthma Immunol 2013; 110: 65-69):
PEARLS IN ALLERGY AND IMMUNOLOGY February 2013
10. Juan Carlos Aldave Becerra, MD
Allergy and Clinical Immunology
Rebagliati Martins National Hospital, Lima-Peru
• Mosquitoes: class Insecta, order Diptera, family Culicidae; >3,500 species worldwide; need
aquatic habitats; both sexes feed on plant juices for energy; females of most species require a
blood-meal after copulation to complete egg development; 50-500 eggs are placed onto water
surfaces or moist soil; Aedes and Culex are the most common genera in North America.
• Mosquito saliva contains >30 proteins that facilitate feeding (antiplatelet, anticoagulant and
vasodilator properties); many of them are allergenic.
• Typical reactions to mosquito bites: 1) Immediate reaction (80% of bitten subjects): 2-10 mm
wheals with surrounding erythema peaking in 20-30 minutes; correlates with saliva-specific IgE
and IgG. 2) Delayed reaction (60% of individuals): 2-10 mm pruritic papules peaking at 24-36
hours and diminishing in several days; correlates with saliva-specific IgG and T cells.
• Large local reactions (2-5% of bitten subjects): 1) Immediate: erythematous pruritic swelling >3
cm occurring in minutes to hours at the site of a bite; correlates with saliva-specific IgE and IgG.
2) Delayed: papular, vesicular, blistering, bullous or ecchymotic, lesions that persist for days or
weeks; correlates with saliva-specific IgG and T cells.
• Skeeter syndrome: large local reactions accompanied by fever; may mimic cellulitis; resolve in
3-10 days; correlates with saliva-specific IgE and IgG.
• Anaphylactic reactions: extremely rare; risk factors: high exposure, lack of acquired immunity
(young children and immigrants).
• Lymphoproliferative and hemophagocytic syndromes: might occur in patients with Epstein-Barr
virus (EBV)-associated lymphoproliferative diseases; hypothesis: repeated activation of saliva-
specific CD4+ T cells, which induce reactivation of latent EBV in NK cells.
• Natural history of mosquito bite reactions in an individual progress through 5 stages: 1) no
reaction (first exposure) → 2) delayed reactions only → 3) immediate reactions followed by
delayed reactions at the same site → 4) immediate reactions only → 5) no reaction
(desensitization, it may take 2-20 years).
• Diagnosis of mosquito allergy is mainly clinical. Patients with typical reactions should not be
labeled as “allergic”; this term should be reserved for those with large local, atypical, or
systemic reactions.
• In patients with a history of severe or atypical reactions, diagnostic testing might be helpful.
Currently available tests (skin testing with whole-body extracts, in vitro detection of specific IgE)
lack adequate sensitivity and specificity.
• New approaches for diagnosis: skin tests with standardized and recombinant allergens;
mosquito bite testing (problems: trapping female insects, risk of eliciting severe reactions, risk of
disease transmission; it may be considered in research to confirm clinical sensitivity).
• Treatment: avoidance (mosquito reduction, reduction of standing water, protective clothing,
chemical repellants, mosquito netting, sleeping indoors); medication (prophylactic
antihistamines, topical steroids, oral steroids, antipyretics for Skeeter syndrome, antibiotics if
secondary bacterial infection occurs, epinephrine); immunotherapy (whole-body mosquito
extracts are not standardized, recombinant allergens should be considered).
PEARLS IN ALLERGY AND IMMUNOLOGY February 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.
• N,N-diethyl-m-toluamide (DEET): the most effective insect repellant for skin or clothing;
indicated for children >2 years old; appropriate concentrations between 10-30%, higher
concentrations can cause systemic toxic effects, dermatitis or bullous eruptions.
• Permethrin 0.5% may be applied to clothes and bed nets 6 hours before wear to ↑ protection.
• PERSISTENT PAPILLOMA AND POLYOMA VIRUS INFECTION IN COMMON VARIABLE
IMMUNODEFICIENCY (CVID) WITH PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY
(Nabavi M, Arshi S, Fallahpour M, Esmaeilzadeh H. Ann Allergy Asthma Immunol 2013; 110: 119-
120):
• CVID: heterogeneous syndrome characterized mainly by hypogammaglobulinemia and
impaired specific antibody responses; higher risk of infections, malignancy and autoimmunity.
• Progressive multifocal leukoencephalopathy (PML): opportunistic demyelinating CNS disease
caused by John Cunningham (JC) virus (polyoma group DNA virus); usually affects individuals
with profound cellular immunosuppression.
• Authors report a 29-year-old woman with CVID and PML. Clinical history: recurrent
sinopulmonary infections from 3 years old; thrombocytopenia and splenomegaly from 7 years
old; splenectomy at 9 years old; initial diagnosis: selective IgA deficiency; meningitis at 15 and
18 years old; diagnosis of CVID at 18 years old; large palmar and plantar planar warts at 22
years old; 1 episode of left knee septic arthritis; PML diagnosed at 28 years old (dysarthria,
ataxia, apraxia, radiographic abnormalities, positive PCR for JC virus in CSF).
• SHOULD EXHALED NITRIC OXIDE BE PART OF ROUTINE ASTHMA MANAGEMENT? (Jain, MD
Peter Boggs, MD Myron Zitt, MD. Ann Allergy Asthma Immunol 2013; 110: 129-130):
• Proposed utility of FeNO measurements: support diagnosis of asthma; support differential
diagnosis; monitor airway inflammation; fine-tune ICS dosing. Its real value is controversial.
• SUCCESS WITH IMMUNOMODULATORY THERAPIES IN THE TREATMENT OF
RECALCITRANT CHRONIC URTICARIA (CU) (Pongonis RM, Fahrenholz JM. Ann Allergy Asthma
Immunol 2013; 110: 123-124):
• CU: 30% of patients are refractory to antihistamines; many patients use oral steroids.
Immunomodulatory therapies may improve CU symptoms and decrease steroid use.
• Authors report 47 patients with antihistamine-refractory CU who received immunomodulatory
therapies. 1st
choice: hydroxychloroquine or sulfasalazine; 2nd
choice: mycophenolate mofetil,
cyclosporine or tacrolimus; 3rd
choice: omalizumab → Age average: 44 years old; 69% of
patients were female; 89% of patients were taking daily or frequent steroids.
• Clinical benefit → cyclosporine: 88% of treated patients; sulfasalazine: 75%; tacrolimus: 60%;
hydroxychloroquine: 56%; mycophenolate mofetil: 55%; omalizumab: 100% (only 3 patients).
• Adverse events that required stopping therapy → hydroxychloroquine: 2 patients with drug
eruptions, 1 patient with a mucosal reaction; sulfasalazine: 1 patient with gastrointestinal
symptoms; cyclosporine: 1 patient with hypertension.
• Cyclosporine is the only immunomodulatory therapy that has RCT data to support its use in CU.
PEARLS IN ALLERGY AND IMMUNOLOGY February 2013
12. Juan Carlos Aldave Becerra, MD
Allergy and Clinical Immunology
Rebagliati Martins National Hospital, Lima-Peru
• Omalizumab is being evaluated in a phase 3 clinical trial for treatment of CU.
• WHEAT-DEPENDENT EXERCISE-INDUCED ANAPHYLAXIS (WDEIA) IN ELDERLY PATIENTS
(Pérez-Rangel I, Gonzalo-Garijo MA, Pérez-Calderón R, Zambonino MA, Corrales-Vargas SI. Ann
Allergy Asthma Immunol 2013; 110: 121-122):
• Food-dependent exercise-induced-anaphylaxis is caused by aerobic exercise within 2-4 hours
after food ingestion; variable severity; usually occurs in adolescents and young adults.
• Authors report 2 elderly patients (85-year-old woman and 79-year-old man) with WDEIA after
mild physical activity. Diagnosis was confirmed by detection of specific IgE against recombinant
omega-5 gliadin. Patients have remained asymptomatic by avoiding any significant physical
activity for at least 3 hours after wheat ingestion.
• The concept of exercise is not well defined for elderly patients. Proposed new terminology:
“activity-dependent wheat allergy”.
PEARLS IN ALLERGY AND IMMUNOLOGY February 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.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY:
• ABERRANT GLYCOSYLATION OF IGA IN WISKOTT-ALDRICH SYNDROME (WAS) AND X-
LINKED THROMBOCYTOPENIA (XLT) (Shimizu M, Kanegane H, Wada T, Motoyoshi Y, Morio T,
Candotti F, Yachie A. J Allergy Clin Immunol 2013; 131: 587-590):
• WAS: X-linked disorder; mutation in the WAS gene; triad of thrombocytopenia, eczema, and
susceptibility to infection. XLT: attenuated form of WAS with minimal or no immunodeficiency.
• Autoimmune complications occur in 40-70% of WAS/XLT patients. Glomerulonephritis occur in
3.5-19% of patients. IgA nephropathy (IgAN) is very common.
• Authors report 26 patients with WAS or XLT → 11 patients had autoimmune complications
(IgAN, vasculitis, arthritis, colitis, autoimmune hemolytic anemia and thrombocytopenia); these
patients had increased levels of: a) galactose-deficient IgA, and b) IgG-IgA circulating immune
complexes, in an age-dependent manner.
• Hypothesis: WAS mutation → aberrant glycosylation of IgA → increased immune-mediated
glomerulonephritis. Mechanisms of aberrant glycosylation of IgA remain unclear.
• ANTIGEN-SPECIFIC T-CELL RESPONSES IN PATIENTS WITH NON–IGE-MEDIATED
GASTROINTESTINAL FOOD ALLERGY ARE PREDOMINANTLY SKEWED TO TH2 (Morita H,
Nomura I, Orihara K, Yoshida K, Akasawa A, Tachimoto H, Ohtsuka Y, Namai Y, Futamura M,
Shoda T, Matsuda A, Kamemura N, Kido H, Takahashi T, Ohya Y, Saito H, Matsumoto K. J Allergy
Clin Immunol 2013; 131: 590-592):
• Non–IgE-mediated GI food allergies: food protein–induced enterocolitis syndrome, food
protein–induced proctocolitis, food protein–induced enteropathy; underlying mechanisms are
not well defined, except for an important role of TNF-α; TH2 cells are thought not to be involved.
• Authors detect antigen-specific TH2 cell responses in infants with non–IgE-mediated GI food
allergies.
• ATOPIC DERMATITIS: A PRACTICE PARAMETER UPDATE 2012 (Schneider L, Tilles S, Lio P,
Boguniewicz M, Beck L, LeBovidge J, Novak N. J Allergy Clin Immunol 2013; 131: 295-299):
• Authors present a 32-page comprehensive document about atopic dermatitis (51 Summary
Statements), in behalf of the American Academy of Allergy, Asthma & Immunology (AAAAI) and
the American College of Allergy, Asthma & Immunology (ACAAI).
• Atopic dermatitis: 10-20% of children, 1-3% of adults; pathogenic factors: atopy, defects in the
skin barrier and humidity, bacterial and fungal colonization of the skin, dysregulated innate and
adaptive responses, increased early Th2 and Th22 responses, autoreactivity, stress;
management: trigger avoidance, measures to restore skin barrier function, antiinflammatory
medication.
• CLASSIFICATION OF PRIMARY IMMUNODEFICIENCIES: NEED FOR A REVISED APPROACH?
(Maggina P, Gennery AR. J Allergy Clin Immunol 2013; 131: 292-294):
• The main purpose of PID classification is to define the natural history and the most appropriate
treatment for each PID.
PEARLS IN ALLERGY AND IMMUNOLOGY February 2013
14. Juan Carlos Aldave Becerra, MD
Allergy and Clinical Immunology
Rebagliati Martins National Hospital, Lima-Peru
• Why PID classification is difficult? a) Heterogeneity (current IUIS classification lists 188 PIDs);
b) Defects in the same gene can cause different clinical phenotypes; c) Defects in different
genes can result in the same clinical or laboratory phenotype.
• Defects in RAG1 and RAG2 can result in different clinical phenotypes → a) T-B-NK+ SCID; b)
Omenn syndrome; c) Combined immune deficiency (CID) with CMV infection and Tγδ
lymphocyte expansion; d) CID with cutaneous granulomatous lesions.
• Omenn syndrome can result from defects in: RAG1, RAG2, DLCRE1C, IL2RG, IL7R, ADA,
LIG4, RMRP7 (cartilage-hair hypoplasia).
• SCID can evolve into Omenn syndrome after antigenic triggering.
• Defects in WAS can result in different clinical phenotypes → a) Wiskott-Aldrich syndrome (loss-
of-function mutations); b) X-linked thrombocytopenia (loss-of-function mutations); c) X-linked
severe congenital neutropenia (gain-of-function mutations).
• Defects in STAT1 can result in different clinical phenotypes → a) Autosomal dominant gain-of-
function mutations: chronic mucocutaneous candidiasis, autoimmunity; b) Autosomal dominant
loss-of-function mutations: susceptibility to mycobacterial and Salmonella infection; c)
Autosomal recessive loss-of-function mutations: severe viral or mycobacterial disease.
• New-generation and whole-exome sequencing will help to detect novel defects in well-known
genes and to discover new PID-causing genes.
• Does it matter whether a gene defect results in SCID, leaky SCID, atypical SCID, profound CID,
or late-onset CID? It matters only if the treatment approach will differ. Multicenter clinical trials
are required to define the most appropriate treatment for each PID.
• COMBINED DOCK8 AND CLEC7A MUTATIONS CAUSING IMMUNODEFICIENCY IN 3
BROTHERS WITH DIARRHEA, ECZEMA, AND INFECTIONS (Dinwiddie DL, Kingsmore SF,
Caracciolo S, Rossi G, Moratto D, Mazza C, Sabelli C, Bacchetta R, Passerini L, Magri C, Bell CJ,
Miller NA, Hateley SL, Saunders CJ, Zhang L, Schroth GP, Barlati S, Badolato R. J Allergy Clin
Immunol 2013; 131: 594-597):
• Authors report 4 brothers from a consanguineous family → severe eczema, milk and egg
allergies, recurrent infections, intractable diarrhea, failure to thrive, lymphoma, severe T-cell
lymphopenia. 2 patients underwent successful HSCT from a matched unrelated donor.
• Genetic sequencing showed: 1) a mutation in CLEC7A (C-type lectin domain family 7, member
A), also known as dectin-1, associated with familiar CMC; b) a novel mutation in DOCK8
(dedicator of cytokinesis 8).
• Exome sequencing should be considered in patients with atypical presentations of PID to
examine possible mutations in >1 locus.
• DISSEMINATED MYCOBACTERIUM GENAVENSE INFECTION AFTER IMMUNOSUPPRESSIVE
THERAPY SHOWS UNDERLYING NEW COMPOSITE HETEROZYGOUS MUTATIONS OF β1
SUBUNIT OF IL-12 RECEPTOR GENE (Tassone L, Carvalho ACC, Calabresi A, Tortoli E, Apostoli
A, Scomodon O, Spina C, Vairo D, Villanacci V, Matteelli A, Badolato R. J Allergy Clin Immunol
2013; 131: 607-610):
PEARLS IN ALLERGY AND IMMUNOLOGY February 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.
• Authors report a 32-yr-old woman with autoimmune hepatitis who had received
immunosuppressive therapy with corticosteroids and azathioprine for 9 years → she presented
with fever, abdominal lymphadenopathy and diarrhea → bone marrow, liver, lymph node and
duodenum biopsies showed macrophages containing acid-fast bacilli → Mycobacterium
genavense DNA was detected → laboratory analysis of patient’s cells showed defective IFN-γ
production in response to IL-12, lack of IL-12Rβ1 expression and impaired STAT-4
phosphorylation after stimulation with IL-12 → genetic sequencing showed a composite
heterozygous mutations of IL12RB1 gene.
• IL-12Rβ1 deficiency: most patients present with isolated BCG infection; some patients present
with infections caused by environmental mycobacteria, M tuberculosis, Salmonella, Klebsiella or
Nocardia; incomplete clinical penetrance; environmental factors may trigger disseminated
infections (e.g. subcutaneous injection of BCG, use of immunosuppressant drugs).
• MSMD (Mendelian susceptibility to mycobacterial diseases) may present as disseminated
mycobacterial infection in patients receiving immunosuppressive treatment.
• FORKHEAD BOX PROTEIN 3 (FOXP3) HYPERMETHYLATION IS ASSOCIATED WITH DIESEL
EXHAUST EXPOSURE AND RISK FOR CHILDHOOD ASTHMA (Brunst KJ, Leung YK, Ryan PH,
Khurana Hershey GK, Levin L, Ji H, LeMasters GK, Ho SM. J Allergy Clin Immunol 2013; 131: 592-
594):
• Traffic-related air pollutants, such as diesel exhaust particles (DEP), contribute to pathogenesis
of wheezing and asthma in early childhood.
• Authors report a study in 92 asthmatic children → children with increased FOXP3 methylation
were 2 times more likely to have asthma than children with lower FOXP3 methylation.
• Chronic DEP exposure during childhood → FOXP3 methylation → reduced FOXP3 expression
→ increased risk for persistent wheezing and asthma.
• New strategy for asthma prevention and treatment: upregulate FOXP3 → expand Treg cells.
• GENETIC VARIATION IN THE TOLL-LIKE RECEPTOR SIGNALING PATHWAY IS ASSOCIATED
WITH CHILDHOOD ASTHMA (Pandey RC, Michel S, Tesse R, Binia A, Schedel M, Liang L, Klopp
N, Franke A, von Berg A, Bufe A, Rietschel E, Heinzmann A, Laub O, Simma B, Frischer T, Genuneit
J, Illig T, Kabesch M. J Allergy Clin Immunol 2013; 131: 602-605):
• Certain microbial exposure in early life → TLR activation → modulation of the immune system
→ less atopy and asthma.
• Asthma has been associated with genetic polymorphisms in TLR2, TLR4, TLR7, TLR8, TLR9.
• Authors evaluated the association between asthma and SNPs in 41 genes from TLR-mediated
signaling cascades → asthma was associated with SNPs in >20 genes; association for atopic
asthma was distinct from nonatopic asthma, only partially overlapping → different TLR
signaling mechanisms might be involved in the pathogenesis of atopic and nonatopic asthma.
• PRIMARY IMMUNODEFICIENCIES: A RAPIDLY EVOLVING STORY (Parvaneh N, Casanova JL,
Notarangelo LD, Conley ME. J Allergy Clin Immunol 2013; 131: 314-323):
PEARLS IN ALLERGY AND IMMUNOLOGY February 2013
16. Juan Carlos Aldave Becerra, MD
Allergy and Clinical Immunology
Rebagliati Martins National Hospital, Lima-Peru
• New PIDs are being discovered at an ever-increasing rate. Authors review 19 novel PIDs that
have been discovered after the release of the last IUIS classification report.
• Each new PID provides valuable insights into how our immune system normally works.
• PROPHYLACTIC THERAPY IN CHILDREN WITH HEREDITARY ANGIOEDEMA (HAE) (Farkas H,
Csuka D, Zotter Z, Varga L, Füst G. J Allergy Clin Immunol 2013; 131: 579-582):
• HAE: recurrent attacks of angioedema without urticaria due to C1-inhibitor deficiency; 50% of
cases initiate in childhood or adolescence; 50% of patients may experience a life-threatening
attack; management: treat and prevent attacks; prophylaxis in children is difficult because of
few suitable medications and low safety profile.
• Authors report their experience managing 48 pediatric patients (<18 yr old) with HAE, and
present an algorithm for HAE prophylaxis in children.
• HAE prophylaxis in children: a) Antifibrinolytics: agents of choice; rarely contraindicated (e.g.
thrombophilia). b) Anabolic androgens: usually contraindicated; they may be necessary in a
proportion of cases; danazol appeared well tolerated at the lowest effective dose. c) Human
plasma-derived C1-INH: good option; problem: cost.
• TGF-β1 POLYMORPHISMS AND ASTHMA SEVERITY, AIRWAY INFLAMMATION, AND
REMODELING (Ierodiakonou D, Postma DS, Koppelman GH, Gerritsen J, ten Hacken NHT, Timens
W, Marike Boezen H, Vonk JM. J Allergy Clin Immunol 2013; 131: 582-585):
• Asthma: chronic inflammation in the airways → release of cytokines and growth factors →
remodeling.
• TGF-β1 levels in the airways are increased in asthma. Actions: regulatory, profibrotic.
• Authors show that TGFB1 SNPs are significantly associated with asthma severity, airway
inflammation and remodeling.
• TICK-BORNE ENCEPHALITIS VIRUS VACCINE AS ADDITIONAL ALTERNATIVE NEOANTIGEN
FOR THE CLINICAL IMMUNOLOGIST’S TOOLBOX (Seidel MG, Planitzer CB, Kreil TR, Förster-
Waldl E. J Allergy Clin Immunol 2013; 131: 617):
• Substitution therapy with IgG provides antibodies against the majority of pathogens → how to
test active antibody response in patients who receive regular IgG substitution therapy? → using
neoantigens (antigens to which the general population is usually not exposed).
• Neoantigens: rabies virus vaccine; the nonlicensed artificial antigens bacteriophage 4X174 and
keyhole limpet hemocyanin; tick-borne encephalitis virus (TBEV) vaccine.
• TBEV vaccine: licensed and easily available in most European countries; routine laboratory
tests to quantify the vaccine response exist.
• ζ CHAIN–ASSOCIATED PROTEIN OF 70 KDA (ZAP70) DEFICIENCY IN HUMAN SUBJECTS IS
ASSOCIATED WITH ABNORMALITIES OF THYMIC STROMAL CELLS (Poliani PL, Fontana E,
Roifman CM, Notarangelo LD. J Allergy Clin Immunol 2013; 131: 597-600):
PEARLS IN ALLERGY AND IMMUNOLOGY February 2013
17. 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.
• Thymic stromal cells: cortical thymic epithelial cells (cTECs), medullary TECs (mTECs) and
dendritic cells (DCs). cTECs → differentiation and positive selection of thymocytes. mTECs and
DCs → negative selection of self-reactive T cells; generation of Treg cells.
• A subset of mTECs express AIRE (autoimmune regulator), a transcription factor that promotes
expression of tissue-restricted antigens, important for negative selection of autoreactive T cells.
Mature mTECs express TSLP and involucrin, important cytokines for DC function.
• 3 major thymic DCs: myeloid DCs, plasmacytoid DCs, Langerhans cells. Interaction between
XCL1 (secreted by mTECs) and XCR1 (expressed in DCs) attract DCs to the deeper medulla.
• Cross-talk between thymocytes and mTECs is essential for mTEC maturation and immune
tolerance induction → several SCID, including Omenn syndrome, are associated with ↓
differentiation of mTECs, ↓ expression of AIRE and ↓ thymic DCs.
• Authors evaluated the thymus of 2 infants with ZAP70 deficiency (recurrent infections,
lymphadenopathy, small-sized thymic shadow, reduced CD8+ lymphs, impaired function of
CD4+ lymphs) → ZAP70 deficiency was associated with: a) ↓ terminal differentiation of mTECs
(minimal amounts of TLSP and involucrin); b) ↓ numbers of AIRE+ mTECs; c) ↓ medullary DCs;
d) ↓ thymic FOXP3+ Treg cells → ZAP70 deficiency might predispose to autoimmunity
(currently there is little clinical evidence, possibly due to the rarity of the disease or because
most patients receive HSCT in infancy, before autoimmunity could develop).
• Hypothesis: ZAP70 deficiency → CD4+ T cells are unable to provide adequate signals to
support terminal differentiation of mTECs.
PEARLS IN ALLERGY AND IMMUNOLOGY February 2013
18. Juan Carlos Aldave Becerra, MD
Allergy and Clinical Immunology
Rebagliati Martins National Hospital, Lima-Peru
PEDIATRIC ALLERGY AND IMMUNOLOGY:
• A PROPOSED EXPLANATION FOR INCREASED RISK OF ACTIVE TUBERCULOSIS IN
CHILDREN WITH ALLERGIC DISEASE (Eisenhut M. Pediatr Allergy Immunol 2013: 24: 98):
• A recent large study reported significant association between tuberculosis and allergic disease.
• Hypothesis: respiratory allergies → high IL-4 production in the airways → 1st
mechanism: IL-4
enhances endocytosis via macrophage’s mannose receptor → mannose receptor binds
mycobacterial lipoarabinomannan → increased entry of M tuberculosis into macrophages. 2nd
mechanism: IL-4 reduces nitric oxide synthase expression → reduced IFN-γ-induced nitric
oxide → decreased intracellular killing of M tuberculosis.
• IL-4 inhibitors (anti-IL-4, soluble IL-4 receptor) are being developed to treat asthma. They may
be useful for tuberculosis.
• C1-INH CONCENTRATE FOR TREATMENT OF ACUTE HEREDITARY ANGIOEDEMA: A
PEDIATRIC COHORT FROM THE I.M.P.A.C.T. STUDIES (Schneider L, Hurewitz D, Wasserman R,
Obtulowicz K, Machnig T, Moldovan D, Reshef A, Craig TJ. Pediatr Allergy Immunol 2013: 24: 54–
60):
• Authors report 7 patients (10-18 years old) from the IMPACT 1 study who received a single
injection of pdC1-INH concentrate (Berinert®, CSL Behring) 20 U/kg for type I or II HAE attacks
→ Median time to onset of relief: 0.42 h; median time to complete resolution: 8.08; no patient
had worsening of symptoms during the 0–4-h assessment period.
• Authors report 9 patients (10-18 years old) from the IMPACT 2 study who received a single
injection of pdC1-INH concentrate (Berinert®, CSL Behring) 20 U/kg for type I or II HAE attacks
→ Median time to onset of relief: 0.49 h; median time to complete resolution: 14.1 h.
• Outcomes with pdC1-INH treatment of HAE attacks in children were similar to adult’s outcomes.
• DESENSITIZATION TO ANTIBIOTICS IN CHILDREN (Cernadas JR. Pediatr Allergy Immunol 2013:
24: 3–9):
• Drug hypersensitivity reactions can occur to almost all drugs. More common drugs: β-lactams,
sulfanilamides, NSAIDs. Incidence in children: 0.75-4.5%.
• Individual with suspected drug hypersensitivity (child or adult) → skin tests (intradermal tests
are difficult to perform in children); in vitro tests; drug challenges (may be performed in a proper
hospital setting during diagnostic workup or delayed until the patient requires the drug).
• Individual with confirmed drug hypersensitivity (child or adult) → avoid the drug; give a safe and
effective alternative drug → desensitize when there is no alternative treatment.
• Drug desensitization: induction of transient tolerance to a drug; tolerance can only be
maintained by continuous drug administration; mainly performed in IgE-mediated reactions but
also seems to work for non-IgE reactions; contraindicated in severe immunocytotoxic reactions,
vasculitis or bullous skin diseases; mechanisms are not well known (IgE may be neutralized by
the increasing dose of antigen; mast cells and basophils may be slowly degranulated).
• Desensitization protocols in children are similar to adult’s, differing only in the final dose.
PEARLS IN ALLERGY AND IMMUNOLOGY February 2013
19. 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.
• Serum sickness-like illness occurs in 0.06% of children receiving cefaclor; possible mechanism:
cytotoxic effect of the drug.
• Amoxicillin and ampicillin often induce rash in patients with EBV infection. Infections can induce
an inflammatory state that activates T cells and predispose to drug reaction.
• General rules for rapid drug desensitization: 1) be sure that the drug is irreplaceable; 2) assume
that it is a risky procedure; 3) evaluate individual risk/benefit for the procedure, benefits must
outweigh risks; 4) get informed consent; 5) be prepared to manage an acute hypersensitivity
reaction; 6) monitor the patient continuously; 7) educate nurses and parents to recognize early
signs of a hypersensitivity reaction; 8) desensitization for severe reactions should be performed
in ICU; 9) follow available desensitization protocols, if they exist; 10) initial dose depends on the
patient’s history (usually 1/10.000; up to 1/1.000.000 when there was a history of anaphylaxis).
• Desensitization to penicillin: oral route seems to be safer (less prone to produce multivalent
penicillin conjugates); mild reactions occur in 30–80% of patients; most procedures are
completed with success.
• Patients with cystic fibrosis: high prevalence (up to 70%) of allergic reactions to antibiotics,
especially β-lactams, in part because of frequent use. Many patients need desensitization
procedures because of frequent requirement of specific antipseudomonal antibiotics; impaired
lung function increases the procedure’s risk.
• Tuberculosis (TBC) treatment requires administration of multiple drugs simultaneously →
hypersensitivity reactions occur in up to 5% of patients. Immediate and non-immediate
reactions (mostly urticarial rashes) are seen with these drugs, predominantly with rifampicin.
• Reaction to TBC treatment → stop all drugs and reintroduce them one at a time, with a 4–5
days interval. In some circumstances (e.g. tuberculous meningitis) it is not possible to stop all
drugs, so only the most probable causal drug(s) should be stopped.
• Both successful and unsuccessful desensitization outcomes should be published, to establish
the most efficient and safer protocols.
• ORAL FOOD DESENSITIZATION IN CHILDREN WITH IGE-MEDIATED HEN’S EGG ALLERGY: A
NEW PROTOCOL WITH RAW HEN’S EGG (Meglio P, Giampietro PG, Carello R, Gabriele I,
Avitabile S, Galli E. Pediatr Allergy Immunol 2013: 24: 75–83):
• Hen’s egg allergy (HEA): 1–2% of young children; 4% of children outgrow HEA by the age of 4,
26% by the age of 8, 48% by the age of 12 and 68% by the age of 16; current treatment:
avoidance (problems: significant dietary limitation, decreased quality of life, psychological
problems), self-injectable epinephrine for severe allergy.
• Authors report a 6-month ‘in home’ protocol that successfully desensitized 8 out of 10 children
(>4 years old) with moderate-severe IgE-mediated HEA.
• Active group: 8 children (80%) achieved daily intake of 25 ml; 1 child (10%) tolerated 2 ml/day;
1 child failed the desensitization. Control group: only 2 children (20%) could tolerate hen’s egg.
• POSITIVE NICKEL PATCH TESTS IN INFANTS ARE OF LOW CLINICAL RELEVANCE AND
RARELY REPRODUCIBLE (Mortz CG, Kjaer HF, Eller E, Osterballe M, Norberg LA, Høst A,
Bindslev-Jensen C, Andersen KE. Pediatr Allergy Immunol 2013: 24: 84–87):
PEARLS IN ALLERGY AND IMMUNOLOGY February 2013
20. Juan Carlos Aldave Becerra, MD
Allergy and Clinical Immunology
Rebagliati Martins National Hospital, Lima-Peru
• Authors report 562 children who were patch tested with nickel sulphate → 26 children had a
positive reaction at 12 and 18 months old → patch tests were repeated at 3 and 6 years old in
21 of those children → only 2 children had reproducible positive reactions.
• Repeated nickel patch tests did not cause sensitization in infants; positive reactions were
probably of irritant or non-specific nature.
• SAFETY OF MOMETASONE FUROATE NASAL SPRAY IN THE TREATMENT OF NASAL
POLYPS IN CHILDREN (Chur V, Small CB, Stryszak P, Teper A. Pediatr Allergy Immunol 2013: 24:
33–38):
• Nasal polyposis: 2–4% of the general population; 0.1% of children; symptoms: rhinorrhea, nasal
congestion, loss of smell; might be associated with asthma and allergy; ↓ quality of life.
• In the US, mometasone furoate nasal spray (MFNS) is approved to treat: 1) nasal polyposis in
individuals ≥18 years old; 2) allergic rhinitis in individuals ≥2 years old.
• Authors report 46 children (6–11 years old) and 81 teens (12-17 years old) with bilateral nasal
polyps who received MFNS for 4 months → MFNS was safe and effective to treat nasal polyps,
even at double the recommended pediatric dosage for allergic rhinitis.
• SPECIFIC ORAL TOLERANCE INDUCTION WITH RAW HEN’S EGG IN CHILDREN WITH VERY
SEVERE EGG ALLERGY: A RANDOMIZED CONTROLLED TRIAL (Dello Iacono I, Tripodi S,
Calvani M, Panetta V, Verga MC, Miceli Sopo S. Pediatr Allergy Immunol 2013: 24: 66–74):
• Authors report a 6-month protocol that partially desensitized 9 out of 10 children (5-11 years
old) with very severe IgE-mediated hen’s egg allergy (HEA), using raw HE emulsion.
• Active group: 9 children (90%) achieved partial tolerance (at least 10 ml, but <40 ml of raw HE
emulsion in a single dose); 1 child (10%) tolerated only 5 ml/day; side effects occurred in all
children. Control group: the 10 children did not tolerate hen’s egg.
• WHEN SHOULD ADRENALINE BE GIVEN AND BY WHOM? (Dreborg S. Pediatr Allergy Immunol
2013: 24: 97–98):
• When should adrenaline be administered? At early symptoms of anaphylaxis (itching of the
throat, soles, the whole body or hacking cough), especially when there is a probable trigger
(e.g. drug, food, insect sting). The problem is to better define which early symptoms indicate
anaphylaxis.
• Who should be trained to administer adrenaline to children and adolescents? Patient (school
children or adolescent), parents, teachers, school nurses and caregivers.
PEARLS IN ALLERGY AND IMMUNOLOGY February 2013