A World Allergy Organization International Survey on Diagnostic Procedures and Therapies in Drug Allergy/Hypersensitivity

OBJECTIVE: To study the diagnostic and treatment modalities used in drug allergy/hypersensitivity among members of the World Allergy Organization (WAO). METHODS: A questionnaire comprising 39 questions was circulated electronically to member societies, associate member societies, and regional and affiliate organizations of WAO between June 29, 2009, and August 9, 2009. RESULTS: Eighty-two responses were received. Skin testing was used by 74.7%, with only 71.4% having access to penicillin skin test reagents. In vitro–specific IgE tests were used by 67.4%, and basophil activation test was used by 54.4%. Lymphocyte transformation tests were used by 36.8% and patch tests by 54.7%. Drug provocation tests were used by 68.4%, the most common indication being to exclude hypersensitivity where history/symptoms were not suggestive of drug hypersensitivity/allergy (76.9%). Rapid desensitization for chemotherapy, antibiotics, or biologic agents was used by 69.6%. Systemic corticosteroid was used in the treatment of Stevens–Johnson syndrome by 72.3%, and high-dose intravenous immunoglobulins in toxic epidermal necrolysis by 50.8%. Human leukocyte antigen screening before prescription of abacavir was used by 92.9% and before prescription of carbamazepine by 21.4%. CONCLUSIONS: Results of this survey form a useful framework for developing educational and training needs and for improving access to drug allergy diagnostic and treatment modalities across WAO member societies

A world allergy organization international survey on diagnostic procedures and therapies in drug allergy/hypersensitivity.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.OBJECTIVE: To study the diagnostic and treatment modalities used in drug allergy/hypersensitivity among members of the World Allergy Organization (WAO). METHODS: A questionnaire comprising 39 questions was circulated electronically to member societies, associate member societies, and regional and affiliate organizations of WAO between June 29, 2009, and August 9, 2009. RESULTS: Eighty-two responses were received. Skin testing was used by 74.7%, with only 71.4% having access to penicillin skin test reagents. In vitro-specific IgE tests were used by 67.4%, and basophil activation test was used by 54.4%. Lymphocyte transformation tests were used by 36.8% and patch tests by 54.7%. Drug provocation tests were used by 68.4%, the most common indication being to exclude hypersensitivity where history/symptoms were not suggestive of drug hypersensitivity/allergy (76.9%). Rapid desensitization for chemotherapy, antibiotics, or biologic agents was used by 69.6%. Systemic corticosteroid was used in the treatment of Stevens-Johnson syndrome by 72.3%, and high-dose intravenous immunoglobulins in toxic epidermal necrolysis by 50.8%. Human leukocyte antigen screening before prescription of abacavir was used by 92.9% and before prescription of carbamazepine by 21.4%. CONCLUSIONS: Results of this survey form a useful framework for developing educational and training needs and for improving access to drug allergy diagnostic and treatment modalities across WAO member societies

Профиль аминокислот в диагностике врождённых заболевания обмена веществ

Institute of Mother and Child, Chisinau, Moldova, Scientific Center of Medicine of State University of Medicine and Pharmacy, Chisinau, Moldova, “Petru Poni” Institute of Macromolecular Chemistry, Romanian Academy, Iasi, Romania, “C. D. Nenitescu” Centre of Organic Chemistry, Romanian Academy, Bucharest, RomaniaIntroducere: Erorile înnăscute de metabolism (EIM) reprezintă un grup eterogen fenotipic și genetic de tulburări cauzate de defect într-o cale metabolică cu consecințe defectuoase în funcționarea metabolismului și/sau acumularea de metaboliți intermediari toxici la nivelul organismului. În prezent, sunt descrise în jur de 1015 IEM, în timp ce individual sunt rare, incidență estimată cumulativ este de 1:500-800. Materiale și metode: Cuantificarea aminoacizilor a fost efectuată în plasma a 2 pacienți suspecți pentru o eroare metabolică. Plasma a fost deproteinizată și analizată în vederea cuantificării aminoacizilor prin cromatografie lichidă de înaltă performanță (HPLC) folosind sistemul “Shimadzu LC-20” și “Agilent 1260”. Rezultate și discuții: În rezultatul analizei cromatogramelor obținute au fost identificate concentrații anormal crescute ale unor aminoacizi sugestiv pentru o EIM. În primul caz, aminoacidul fenilalanina avea valori foarte crescute (1064 μmol/L), iar tirozina și aminoacizii concurenți pentru sistemul de transport LNAA (valină, leucină, izoleucină) erau în cantități joase, pacientul facându-se suspect pentru maladia fenilcetonurie (PKU), fiind imediat supus dietoterapiei. Concentrația ridicată de alanină (572 μmol/L) și raportul alanină/lizină crescut de 6,8 a completat profilul investigațiilor metabolice ale pacientului următor cu sugestii importante pentru o eroare metabolică cu implicare mitocondrială. Cuantificarea aminoacizilor la pacienții testați au contribuitt la stabilirea diagnosticului și inițierea terapiei corespunzătoare cu monitorizarea periodica a valorilor aminoacizilor. Concluzie: Identificarea biomarkerilor din spectrul aminoacizilor prin Cromatografie lichidă de înaltă performanță oferă posibilitatea obținerii unui spectru larg de metaboliți utili în stabilirea diagnosticului sau monitorizarea atât a pacientului acut bolnav cât celui supus unei terapii specifice pentru a evalua eficiența tratamentului.Введение: Врождённые заболевания обмена веществ представляют собой гетерогенную группу нарушений, вызванных дефектом метаболического пути с нарушениями метаболизма и/или накоплением токсичных метаболитов в организме. В настоящее время описано около 1015 заболеваний, но кумулятивная частота составляет 1:500-800. Материалы и методы. Количественный анализ аминокислот проводился в плазме 2 пациентов с подозрением на нарушения метаболизма. Плазму депротеинизировали и анализировали для определения аминокислот с помощью высокоэффективной жидкостной хроматографии с использованием систем «Shimadzu LC-20» и «Agilent 1260». Результаты и обсуждение: В результате анализа полученных хроматограмм были выявлены аномально высокие концентрации некоторых аминокислот, наводящие на мысль о наличии врождённые заболеваний обмена веществ. В первом случае было выявлена высокая концентрация фенилаланина (1064 мкмоль/л), а тирозин и конкурирующие аминокислоты для транспортной системы LNAA (валин, лейцин, изолейцин) были в малых количествах, что заставило заподозрть болезнь фенилкетонурию у пациента. Полученные данные определили начало диетотерапии. Высокая концентрация аланина (572 мкмоль/л) и увеличенное соотношение аланин/лизин до 6,8 дополнили профиль метаболических исследований следующего пациента с подозрением на метаболические нарушения с вовлечением митохондрий. Количественное определение аминокислот у испытуемых пациентов способствовало постановке диагноза и началу соответствующей терапии с периодическим мониторингом значений аминокислот. Заключение: Идентификация биомаркеров в спектре аминокислот с помощью высокоэффективной жидкостной хроматографии даёт возможность получить широкий спектр метаболитов, полезных для установления диагноза или мониторинга как при тяжёлых формах болезни пациентов, так и у пациентов, проходящих специальную терапию, для оценки эффективности лечения

Proposal of 0.5 mg of protein/100 g of processed food as threshold for voluntary declaration of food allergen traces in processed food-A first step in an initiative to better inform patients and avoid fatal allergic reactions : A GA(2)LEN position paper

Background Food anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labeling the 14 main allergens used as ingredients in food products is mandatory in the EU, there is no legal definition of declaring potential contaminants. Precautionary allergen labeling such as "may contain traces of" is often used. However, this is unsatisfactory for consumers as they get no information if the contamination is below their personal threshold. In discussions with the food industry and technologists, it was suggested to use a voluntary declaration indicating that all declared contaminants are below a threshold of 0.5 mg protein per 100 g of food. This concentration is known to be below the threshold of most patients, and it can be technically guaranteed in most food production. However, it was also important to assess that in case of accidental ingestion of contaminants below this threshold by highly allergic patients, no fatal anaphylactic reaction could occur. Therefore, we performed a systematic review to assess whether a fatal reaction to 5mg of protein or less has been reported, assuming that a maximum portion size of 1kg of a processed food exceeds any meal and thus gives a sufficient safety margin. Methods MEDLINE and EMBASE were searched until 24 January 2021 for provocation studies and case reports in which one of the 14 major food allergens was reported to elicit fatal or life-threatening anaphylactic reactions and assessed if these occurred below the ingestion of 5mg of protein. A Delphi process was performed to obtain an expert consensus on the results. Results In the 210 studies included, in our search, no reports of fatal anaphylactic reactions reported below 5 mg protein ingested were identified. However, in provocation studies and case reports, severe reactions below 5 mg were reported for the following allergens: eggs, fish, lupin, milk, nuts, peanuts, soy, and sesame seeds. Conclusion Based on the literature studied for this review, it can be stated that cross-contamination of the 14 major food allergens below 0.5 mg/100 g is likely not to endanger most food allergic patients when a standard portion of food is consumed. We propose to use the statement "this product contains the named allergens in the list of ingredients, it may contain traces of other contaminations (to be named, e.g. nut) at concentrations less than 0.5 mg per 100 g of this product" for a voluntary declaration on processed food packages. This level of avoidance of cross-contaminations can be achieved technically for most processed foods, and the statement would be a clear and helpful message to the consumers. However, it is clearly acknowledged that a voluntary declaration is only a first step to a legally binding solution. For this, further research on threshold levels is encouraged.Peer reviewe

Proposal of 0.5 mg of protein/100 g of processed food as threshold for voluntary declaration of food allergen traces in processed food—A first step in an initiative to better inform patients and avoid fatal allergic reactions: A GA²LEN position paper

Background: Food anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labeling the 14 main allergens used as ingredients in food products is mandatory in the EU, there is no legal definition of declaring potential contaminants. Precautionary allergen labeling such as "may contain traces of" is often used. However, this is unsatisfactory for consumers as they get no information if the contamination is below their personal threshold. In discussions with the food industry and technologists, it was suggested to use a voluntary declaration indicating that all declared contaminants are below a threshold of 0.5 mg protein per 100 g of food. This concentration is known to be below the threshold of most patients, and it can be technically guaranteed in most food production. However, it was also important to assess that in case of accidental ingestion of contaminants below this threshold by highly allergic patients, no fatal anaphylactic reaction could occur. Therefore, we performed a systematic review to assess whether a fatal reaction to 5mg of protein or less has been reported, assuming that a maximum portion size of 1kg of a processed food exceeds any meal and thus gives a sufficient safety margin. Methods: MEDLINE and EMBASE were searched until 24 January 2021 for provocation studies and case reports in which one of the 14 major food allergens was reported to elicit fatal or life-threatening anaphylactic reactions and assessed if these occurred below the ingestion of 5mg of protein. A Delphi process was performed to obtain an expert consensus on the results. Results: In the 210 studies included, in our search, no reports of fatal anaphylactic reactions reported below 5 mg protein ingested were identified. However, in provocation studies and case reports, severe reactions below 5 mg were reported for the following allergens: eggs, fish, lupin, milk, nuts, peanuts, soy, and sesame seeds. Conclusion: Based on the literature studied for this review, it can be stated that cross-contamination of the 14 major food allergens below 0.5 mg/100 g is likely not to endanger most food allergic patients when a standard portion of food is consumed. We propose to use the statement "this product contains the named allergens in the list of ingredients, it may contain traces of other contaminations (to be named, e.g. nut) at concentrations less than 0.5 mg per 100 g of this product" for a voluntary declaration on processed food packages. This level of avoidance of cross-contaminations can be achieved technically for most processed foods, and the statement would be a clear and helpful message to the consumers. However, it is clearly acknowledged that a voluntary declaration is only a first step to a legally binding solution. For this, further research on threshold levels is encouraged

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity