AbstractBackgroundIn anaphylaxis, the dosing of injectable epinephrine in medical settings has been arbitrarily recommended to be 0.01 mg/kg of body weight. For ethical reasons, there have been no dose–response studies or double-blind studies performed on patients with active anaphylaxis. Intramuscular delivery of epinephrine has been the standard. Auto-injectors for use in the treatment of anaphylaxis are available in four strengths (0.1, 0.15, 0.3, and 0.5 mg). However, in many countries, only the 0.15 and 0.3 mg strengths are available. Consequently, many adult, heavy patients are prescribed the 0.3 mg dose, which may result in only one-fifth to one-third of the recommended weight-based dose being administered in heavy patients experiencing anaphylaxis. Underdosing may have therefore contributed to mortality in anaphylaxis.ObjectiveTo review the doses of epinephrine recommended for the treatment of anaphylaxis in the community, and assess whether recommendations should be made to increase dosing for heavy adult patients in hopes of avoiding future deaths from anaphylaxis.MethodsWe reviewed multiple national and international recommendations for the dosing of epinephrine. We also reviewed the literature on adverse drug reactions from epinephrine, lethal doses of epinephrine, and epinephrine dose-finding studies.ResultsThe majority of national and regional professional societies and authorities recommend epinephrine delivered by auto-injectors at doses far lower than the generally accepted therapeutic dose of 0.01 mg/kg body weight. Furthermore, we found that the recommendations vary even within regions themselves.ConclusionsWe suggest prescribing more appropriate doses of epinephrine auto-injectors based on weight-based recommendations. There may be some exceptions, such as for patients with heart disease. We hypothesize that these recommendations will lead to improved outcomes of anaphylaxis.

Background For a century, epinephrine has been the drug of choice for acute treatment of systemic allergic reactions/anaphylaxis. For 40 years, autoinjectors have been used for the treatment of anaphylaxis. Over the last 20 years, intramuscular epinephrine injected into the thigh has been recommended for optimal effect. Objective To review the literature on pharmacokinetics of epinephrine autoinjectors. Results Six studies assessing epinephrine autoinjector pharmacokinetics were identified. The studies, all on healthy volunteers, were completed by Simons, Edwards, Duvauchelle, Worm and Turner over the span of 2 decades. Simons et al. published two small studies that suggested that intramuscular injection was superior to subcutaneous injection. These findings were partially supported by Duvauchelle. Duvauchelle showed a proportional increase in C max and AUC 0-20 when increasing the dose from 0.3 to 0.5 mg epinephrine intramuscularly. Turner confirmed these findings. Simons, Edwards and Duvauchelle documented the impact of epinephrine on heart rate and blood pressure. Turner confirmed a dose-dependent increase in heart rate, cardiac output and stroke volume. Based on limited data, confirmed intramuscular injections appeared to lead to faster C max . Two discernable C max’s were identified in most of the studies. We identified similarities and discrepancies in a number of variables in the aforementioned studies. Conclusions Intramuscular injection with higher doses of epinephrine appears to lead to a higher C max . There is a dose dependent increase in plasma concentration and AUC 0-20 . Most investigators found two C max’s with T max 5–10 min and 30–50 min, respectively. There is a need for conclusive trials to evaluate the differences between intramuscular and subcutaneous injections with the epinephrine delivery site confirmed with ultrasound.

Epinephrine autoinjectors should be used for treatment of severe general allergic reactions in the community. Recently, there has been a concern that the autoinjectors are not designed properly for all patients.

Diagnostic allergens are defined as medicinal products in the EU. Marketing authorization by national authorities is necessary; however, diagnostic allergens are not homogeneously regulated in different EU member states. Allergen manufacturers argue with increasing costs forcing them to continuously reduce the diagnostic allergen portfolios offered to allergists. In contrast, EAACI and national European Allergy Societies see the need for the availability of a wide range of high-quality diagnostic allergens for in vivo diagnosis of IgE-mediated allergies not only covering predominant but also less frequent allergen sources. In a recent EAACI task force survey, the current practice of allergy diagnosis was shown to rely on skin tests as first option in almost 2/3 of all types of allergic diseases and in 90% regarding respiratory allergies. With the need to ensure the availability of high-quality diagnostic allergens in the EU, an action plan has been set up by EAACI to analyse the current regulatory demands in EU member states and to define possible solutions stated in this document: (a) simplification of authorization for diagnostic allergens; (b) specific regulation of special types of diagnostic allergens; (c) new models beyond the current model of homologous groups; (d) simplification of pharmacovigilance reporting; (e) reduction of regulation fees for diagnostic allergens; (f) reimbursement for diagnostic allergens. Joining forces of allergists, manufacturers and authorities are of high importance to ensure remaining relevant allergens in the EU markets to facilitate a sustainable and comprehensive service for the diagnosis and treatment of allergic diseases.

In his editorial “Epinephrine needle length in autoinjectors and why it matters” in the Journal of Allergy and Clinical Immunology: In Practice, Song1Song T.T. Epinephrine needle length in autoinjectors and why it matters.J Allergy Clin Immunol Pract. 2018; 6: 1264-1265Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar reviewed the findings of Duvauchelle et al,2Duvauchelle T. Robert P. Donazzolo Y. Loyau S. Orlandini B. Lehert P. et al.Bioavailability and cardiovascular effects of adrenaline administered by anapen autoinjector in healthy volunteers.J Allergy Clin Immunol Pract. 2018; 6: 1257-1263Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar reporting new data on the pharmacokinetics of epinephrine and epinephrine autoinjectors (EAIs). We disagree with a number of Song's interpretations of earlier studies. First, Song claims that when using an EAI, epinephrine is not deposited at the tip of the needle but forced further by high pressure. This finding is from a pig model study where there was no assessment of the impact of muscle fascia. Importantly, Diacono et al3Diacono D. Pumphrey R.S. Sharma V. Arkwright P.D. The deep fascia of the thigh forms an impenetrable barrier to fluid injected subcutaneously by autoinjectors.J Allergy Clin Immunol Pract. 2015; 3: 297-299Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar found that the propulsive force of autoinjectors did not propel the epinephrine through the fascia using a pig model. We agree with the data by Diacono et al suggesting that the needle must pass through the whole muscle fascia and the epimysium to deliver epinephrine into muscle (IM). Secondly, Song claims that the subcutaneous (SC) tissue is compressed by the injection pressure from autoinjectors. It is true that some compression of SC tissue occurs. But on average only 10% of the compression is in the SC tissue and approximately 90% of the compression takes place in the muscle4Dreborg S. Kim L. Tsai G. Kim H. Epinephrine auto-injector needle lengths: can both subcutaneous and periosteal/intraosseous injection be avoided?.Ann Allergy Asthma Immunol. 2018; 120: 648-653.e1Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar (Table I). So compression has a relatively small impact on successful IM delivery. The SC tissue is more compressed in women than in men.Table INew data from the original papers analyzing STMD, STBD min and max and % compression of the subcutaneous tissue in adult women (n = 67) and men (n = 32)VariablenMeanMinMaxSignificancesSTMDmin women6715.46.031.7<.000001WomenSTMDmin men326.93.313.6STMDmin vs STMDmaxSTMDmax women6712.95.027.7<.000001P ≤ .000001STMDmax men326.32.713.7MenSTMDmin vs STMDmaxP ≤ .000001Compression SC % women6715.8−9.548.8<.000001Compression SC % men323.2−1.813.0SC, Subcutaneous; STMD, skin to muscle distance; STBD, skin to bone distance.t-tests were performed. Open table in a new tab SC, Subcutaneous; STMD, skin to muscle distance; STBD, skin to bone distance. t-tests were performed. Thirdly, Song1Song T.T. Epinephrine needle length in autoinjectors and why it matters.J Allergy Clin Immunol Pract. 2018; 6: 1264-1265Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar claims that “It is likely that the propulsive force may be sufficient in some instances to propel epinephrine across the fascia into the IM space” without providing any evidence. We do not believe that EAI given SC will deliver the drug intramuscularly. Song cites Diacono et al,3Diacono D. Pumphrey R.S. Sharma V. Arkwright P.D. The deep fascia of the thigh forms an impenetrable barrier to fluid injected subcutaneously by autoinjectors.J Allergy Clin Immunol Pract. 2015; 3: 297-299Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar who identified that the epinephrine jet does not penetrate the fascia. However, Song did not use Diacono et al's findings when stating his claims. Furthermore, in Duvauchelle et al's study,2Duvauchelle T. Robert P. Donazzolo Y. Loyau S. Orlandini B. Lehert P. et al.Bioavailability and cardiovascular effects of adrenaline administered by anapen autoinjector in healthy volunteers.J Allergy Clin Immunol Pract. 2018; 6: 1257-1263Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar imaging of SC injections does not appear to lead to ultrasound changes in the IM compartment. This suggests that the SC epinephrine did not penetrate into muscle. Lastly, Song claims that estrogens may influence the pharmacokinetics of epinephrine when assessed in these studies that span several minutes only. We cannot rationalize how estrogen would impact epinephrine levels in such studies. We could not find any evidence in the medical literature to support this idea. We conclude that until further human experiments have been performed, the pig model data showing that epinephrine is not forced through the fascia by the high jet pressure should be accepted, that the compression of the SC tissue by EAI is limited, and that there seems to be little difference in tissue compression between men and women. Sten Dreborg: 0000-0002-3544-1557 Harold Kim: 0000-0002-0497-844X Sten Dreborg drafted the correspondence and Harold Kim and Sten Dreborg reviewed the text critically and accepted the final version. ReplyThe Journal of Allergy and Clinical Immunology: In PracticeVol. 7Issue 6PreviewWe appreciate comments from Dreborg and Kim.1 We value their input, but there are additional data that challenge their conclusions. We discuss these data below. Full-Text PDF

The Agency for Healthcare Research and Quality and the National Institute of Allergy and Infectious Diseases organized a workshop to develop trial concepts that could improve the use and effectiveness of aeroallergen immunotherapy (AAIT). Expert groups were formed to accomplish the following tasks: (1) propose a study design to compare the effectiveness and safety of subcutaneous versus sublingual AAIT; (2) propose a study design to compare the effectiveness and safety of AAIT by using 1 or a few allergens versus all or most allergens to which a patient is sensitized; (3) propose a study design to determine whether AAIT can alter the progression of childhood allergic airways disease; and (4) propose a study design to determine the optimal dose and duration of AAIT to achieve maximal effectiveness with acceptable safety. Study designs were presented by the workgroups, extensively discussed at the workshop, and revised for this report. The proposed trials would be of long duration and require large highly characterized patient populations. Scientific caveats and feasibility matters are discussed. These concepts are intended to help the development of clinical trials that can address some of the major questions related to the practice of AAIT for the management and prevention of allergic airways disease.

Allergens are molecules with the capacity to elicit IgE responses in humans. When stimulated with allergens, most allergic patients respond with production of IgE specific for several proteins/allergens in the source material. The standardization of allergen extracts is essential in order to control variability and to achieve consistency and reproducibility in a clinical setting.Because the IgE binding capacity of an allergen extract is related to the content of one or a few major allergens, it is important that the standardization procedure ensures consistency, not only in the overall IgE binding potency, but also in the content and ratio of individual major allergens. Owing to the complexity of allergen extracts, a key element in standardization of allergen extracts is the use of standards.This chapter describes the principles for standardization of allergen extracts to be used by research laboratories. Other chapters in this volume describe in vitro methods in detail.

LRBA deficiency is caused by loss of LRBA protein expression, due to either homozygous or compounds heterozygous mutations in LRBA. LRBA deficiency has been shown to affect vesicular trafficking and autophagy. To date, LRBA has been observed in the cytosol, Golgi apparatus and some lysosomes in LPS-stimulated murine macrophages. The objectives of the present study were to study the LRBA localization in organelles involved in vesicular traffic, phagocytosis, and autophagy in mononuclear phagocytes (MP).We analyzed LRBA colocalization with different endosomes markets using confocal microscopy in MP. We used the autophagy inhibitors to determine the role of LRBA in formation, maturation or degradation of the autophagosome.LRBA intracellular trafficking depends on the activity of the GTPase ADP ribosylation factor-1 (ARF) in MP. LRBA was identified in early, late endosomes but did not colocalize strongly with lysosomal markers. Although LRBA appears not to be recruited during the phagocytic cargo uptake, it greatly colocalized with the microtubule-associated protein 1A/1B-light chain 3 (LC3) under a steady state and this decreased after the induction of autophagy flux. Although the use of inhibitors of lysosome fusion did not restore the LRBA/LC3 colocalization, inhibitors of either early to late endosomes trafficking or PI3K pathway did.Taken together, our results show that LRBA is located in endomembrane system vesicles, mainly in the early and late endosomes. Although LRBA appears not to be involved in the phagocytic uptake, it is recruited in the early steps of the autophagy flux.

BACKGROUND:The variation of needle lengths of epinephrine auto-injectors (EAIs) has not been investigated. OBJECTIVE:To investigate the impact of the variation of the needle length of EAIs. METHODS:Skin-to-muscle (STMD) and skin-to-bone distances (STBD) were measured for 303 children and adolescents and 99 adults. Distance was determined by ultrasound, applying high or low pressure on the probe. The risk of subcutaneous and periosteal/intraosseous injection was calculated using the lower and upper acceptance limits for length of EAI needles as provided for 3 high-pressure EAIs (HPEAI) and 1 low-pressure EAI (LPEAI). RESULTS:The variation in needle length of the HPEAIs are for Epipen Jr/Epipen 5 mm, for Jext 2 mm, for Auvi-Q 2.5 mm, and for the LPEAI, Emerade, 1.5 mm. When using the longest acceptable needles for Epipen Jr, the risk of intraosseous/periosteal penetration was highest in children weighing less than 15 kg at 60% and for Jext at 43%. The risk was low for Auvi-Q and Emerade. The risk of subcutaneous injection was greatest with the shortest needles of the Auvi-Q 0.1 mg at 94% in children weighing less than 15 kg. In adults, the risk of subcutaneous injection using the shortest needles was for Epi-Pen at 41%, Jext at 36%, Auvi-Q at 38%, and Emerade at 12%. CONCLUSION:The variation in needle length of EAIs influences the risk of subcutaneous and intraosseous/periosteal injections. Compared with Epipen Jr, the Auvi-Q 0.1 mg for children weighing less than 15 kg had a low risk of intraosseous/periosteal injection but a very high risk of subcutaneous injection. For adults, there is a significant risk of subcutaneous injection.

Background: Some overweight and obese adults have an increased risk of subcutaneous injection using epinephrine auto injectors (EAIs). Needle lengths of EAIs vary between brands and lots. Objective: To study if BMI or height adds information to define adults at risk of having intraosseous or subcutaneous injection. Methods: Ninety-nine (99) food allergic adult patients, 32 men and 67 women, 18 – 72 years of age, prescribed EAIs were included. The skin to muscle and skin to bone distances were measured by ultrasonography. The effect of injection on naked skin or through thick clothing was analyzed. High and minimal pressure was applied to the ultrasound probe. Results: Two of three men and 1/5 women with BMI <20 had a risk of intraosseous/periosteal injection using the high pressure auto injector Epipen® , thick clothing, 5/8. Injecting through naked skin using the shortest needle, 14/17 obese women had a high risk of subcutaneous injection (overweight 14/23), through thick clothing all 17 obese women would have a risk of subcutaneous injection (overweight 20/23). Injecting with LPEAIs through naked skin, using the shortest needle 8/17 obese and 4/23 overweight women would have a risk of subcutaneous injection, wearing thick clothing, 10/17 obese and 7/23 overweight women. Height had no predictive value. Conclusion: Using high pressure EAIs, high BMI predicted a very high risk for subcutaneous injection in women and in some men. Even injection with low pressure EAIs had some risk of subcutaneous injection, especially when injected through thick clothing. Height had no predictive value. Keywords: Auto-injector; epinephrine; intramuscular; subcutaneous; intraosseous; skin to bone distance; skin to muscle distance; clothing; overweight; obese; adults; women; men.

Salas et al1Salas M. Fernández-Santamaría R. Mayorga C. Barrionuevo E. Ariza A. Posadas T. et al.Use of basophil activation test may reduce the need for drug provocation in amoxicillin-clavulanic allergy.J Allergy Clin Immunol Pract. 2018; 6: 1010-1018Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar published an article in this journal on the value of the basophil activation test (BAT) in the evaluation of amoxicillin-clavulanic acid allergic reactions. Their conclusion is that the sensitivity of BAT is 62% and that BAT is a promising complementary technique. Before discussing sensitivity, the limit between positive and negative test results, that is, the cutoff of the method, must be established. A cutoff limit should differentiate between those with positive reactions according to the method and those in whom the test/stimulation is not different from the background. Normally, the cutoff of in vitro tests is defined by the mean of blank tests + 3.3 SD.2Matsson P.N.J. Hamilton R.G. Esch R.E. Halsey J.F. Homburger H.A. Kleine-Tebbe J. et al.Analytical performance characteristics and clinical utility of immunological assays for human immunoglobulin E (IgE) antibodies and defined allergen specificities: approved guideline. Clinical and Laboratory Standards Institute, Philadelphia2009: 1-160Google Scholar In vivo tests are limited by the highest concentration of allergen available that is not toxic/locally irritating in normal subjects. BAT with aeroallergens can be performed using a wide range of concentrations of allergen and the results are given as the concentration inducing 50% of maximum activation with anti-IgE. The principle is the same as that used for histamine release tests and for in vivo challenge tests defined by their threshold concentrations. This is not possible for drug-stimulated BAT. Much higher concentrations of drugs are needed for basophil activation than are used with aeroallergens. Slightly higher concentrations are cytotoxic, leaving a narrow window, excluding the possibility to use for titration and calculation of threshold concentrations. The sensitivity of BAT depends on the cutoff of the test. Salas et al1Salas M. Fernández-Santamaría R. Mayorga C. Barrionuevo E. Ariza A. Posadas T. et al.Use of basophil activation test may reduce the need for drug provocation in amoxicillin-clavulanic allergy.J Allergy Clin Immunol Pract. 2018; 6: 1010-1018Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar use a stimulation index (SI), that is, the ratio of percent basophils activated by allergen (>5% activation)/percent basophils activated spontaneously. They regard a ratio of 1.5 as positive, but such a cutoff is not well documented. As late as in 2016 European researchers agreed on a more realistic cutoff limit of SI more than 2.3Hoffmann H.J. Knol E.F. Ferrer M. Mayorga L. Sabato V. Santos A.F. et al.Pros and cons of clinical basophil testing (BAT).Curr Allergy Asthma Rep. 2016; 16: 56Crossref PubMed Scopus (21) Google Scholar Using the accepted, but not well-documented, cutoff (SI > 2) instead of an SI of 1.5 would decrease the sensitivity (Figure 1, A). The cutoff of 1.5 for the SI is said to be based on a receiver-operating characteristic curve presented as Figure E2 in the article by Salas et al.1Salas M. Fernández-Santamaría R. Mayorga C. Barrionuevo E. Ariza A. Posadas T. et al.Use of basophil activation test may reduce the need for drug provocation in amoxicillin-clavulanic allergy.J Allergy Clin Immunol Pract. 2018; 6: 1010-1018Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar This involves circular reasoning in that they use a proposed new cutoff and then confirm it in a receiver-operating characteristic curve based on the sensitivity and specificity resulting from the proposed cutoff. Three concentrations were used, with 10 and 25 times difference between the highest and the lowest concentration of amoxicillin and clavulanic acid, respectively.1Salas M. Fernández-Santamaría R. Mayorga C. Barrionuevo E. Ariza A. Posadas T. et al.Use of basophil activation test may reduce the need for drug provocation in amoxicillin-clavulanic allergy.J Allergy Clin Immunol Pract. 2018; 6: 1010-1018Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar This difference is far lower than the variation in sensitivity using in vivo provocation tests, in vitro IgE tests, or histamine release tests.4Dreborg S. Basomba A. Belin L. Durham S. Einarsson R. Eriksson N. et al.Biological equilibration of allergen preparations: methodological aspects and reproducibility.Clin Allergy. 1987; 17: 537-550Crossref PubMed Scopus (53) Google Scholar The variation is at least 4 magnitudes. A value less than the cutoff limit is negative. Negative data can only be presented as negative. Thus, the median cannot be given a value less than the cutoff 2 (or 1.5); it is just negative. In Figure 1, A, all dots and rings lower than 2 (1.5) should be removed (Figure 1, B). The number of negative test results is presented as a number below the graph in Figure 1, B. For the purpose of statistical analysis, negative results are sometimes given a value lower than the cutoff. In this case SI = 1 would be suggested. Normal criteria for documentation of background and degree of sensitivity of BAT cannot be established before a well-documented BAT method has been agreed upon. Use of the Basophil Activation Test May Reduce the Need for Drug Provocation in Amoxicillin-Clavulanic AllergyThe Journal of Allergy and Clinical Immunology: In PracticeVol. 6Issue 3PreviewReports of selective reactions to clavulanic acid (CLV) have increased in recent decades because of its increased prescription in combination with amoxicillin (AX) as AX-CLV. Basophil activation test (BAT) is used for diagnosing beta-lactam immediate hypersensitivity and is the only available in vitro assay for diagnosing patients with immediate hypersensitivity to CLV. However, few studies, and with limited numbers of patients have been published. Full-Text PDF ReplyThe Journal of Allergy and Clinical Immunology: In PracticeVol. 6Issue 3PreviewDreborg1 has expressed concerns regarding our recent article on the value of basophil activation test (BAT) for the evaluation of amoxicillin-clavulanic acid (AX-CLV) allergy.2 Full-Text PDF

Background Epinephrine auto-injectors are expected to deliver the drug intramuscularly. Objective To study whether injection through clothing influences the frequency of subcutaneous and intraosseous/periosteal deposition of epinephrine. Methods Skin to muscle and skin to bone distances were measured for 303 children and adolescents and 99 adults. Distance was determined by ultrasound, with high or low pressure on the ultrasound probe. The risk/percentage of subcutaneous and intraosseous/periosteal injections was calculated using the lower and upper limits for the authority-approved length of EAI needles as provided by two high pressure EAI manufacturers and one low pressure EAI manufacturer. The addition winter clothing on the delivery of epinephrine was illustrated by comparing drug delivery fissue depth with no clothes. Furthermore, the riof non-intramuscular delivery for the shortest and longest approved needle length was calculated. Results When using EpipenJr ® in children < 15 kg the risk of intraosseous/periostal injection was reduced from 1% and 59% for the shortest and longest approved needle length to 0 and 15% with winter clothes. The Auvi-Q ® 0.1 mg had no risk of intraosseous/periosteal injection. However, the subcutaneous deposition risk increased from 94% and 28% to 100% and 99% with winter clothes. The risk of subcutaneous injection using EpipenJr ® in the youngest children increased from 13% and 0% to 81% and 1% with winter clothes, and with Epipen ® in adults from 45% and 17% to 60% and 38%. Emerade ® , had a risk of subcutaneous injection in adults increasing from 14% and 10% to 28% and 21% adding winter clothes. Conclusion The risk of intraosseous/periosteal injections decreases and the risk of subcutaneous injection increases when injecting through winter clothes for all EAIs.

The skin prick/puncture test (SPT) is the most common method within allergology used for screening of sensitization to food allergens and primary diagnostic tool of food allergen sensitization. A positive SPT with food indicates IgE sensitization, i.e., atopy, and possible IgE-mediated allergy. The indication for SPT or conventional in vitro IgE testing has been diagnosis of species specific sensitization or allergy. However, during recent years, component-resolved diagnosis using an allergen chip based technology, ISAC, has made it possible to reveal sensitization to a relatively low number of allergen protein families with cross-reacting molecules within related but even unrelated allergen source materials. This will make SPT important as a screening method for later molecular diagnosis. This chapter discusses the factors influencing SPT as a diagnostic tool in food allergy, the registration, evaluation and interpretation of skin prick/puncture tests in clinical trials as well as in daily practice.

In the European Union (EU), the regulatory framework regarding diagnostic allergen extracts is currently in the process of being implemented at the national level. Due to these regulations, the initial and periodic renewal expenses for the registration of diagnostic allergen extracts may render extract production unprofitable. Consequently, many extracts may be at risk of removal from the market. The current survey, which was conducted by a task force of the European Academy of Allergy and Clinical Immunology, aimed to assess the current practice of allergy diagnosis in Europe. This survey revealed that skin tests continue to be the main diagnostic procedure and are used as the first option in almost two-third of all types of allergic diseases and in 90% of individuals suffering from respiratory allergies. Therefore, there is a need to ensure the availability of high-quality allergen extracts to maintain the common diagnostic procedures used by EU professionals. To reach this goal, it is necessary to align efforts and establish active partnerships between manufacturers, relevant scientific societies, consumer organizations and authorities to maintain the availability of these diagnostic tools.

Background: Skin prick testing is the most common diagnostic tool used by allergists. There are limited, international rules on interpreting and reporting skin test results in a meaningful way. Aim: This communication describes methods to express the results of skin prick tests in a meaningful way. It is recommended to use allergen extracts with defined composition, potency and stability, to keep the precision of SPT within acceptable limits by using duplicate tests, and to regularly calculate the c.v. If duplicate tests cannot be performed for practical and or psychological reasons, e.g. in small children, then it are proposed that regular proficiency tests are performed and reported. The method of estimating the allergen threshold concentration, histamine equivalent allergen concentration Cha, is described Conclusion: By adjusting the allergen wheal response to that of histamine, Cha, differences in techniques between personnel and centres can be minimized and changes in skin reactivity can be calculated as a threshold concentration. To document the skin reactivity and changes over time it is even proposed to report the mean histamine wheal response of groups and of testing personnel at all-time points of therapeutic trials and in practice over time.

Liquid sublingual allergen immunotherapy (SLIT) has been used off-label for decades, and Food and Drug Administration (FDA)-approved grass and ragweed SLIT tablets have been available in the United States since 2014. Potentially life-threatening events from SLIT do occur, although they appear to be very rare, especially for FDA-approved products. Practice guidelines that incorporate safety precautions regarding the use of SLIT in the United States are needed. This clinical commentary attempts to address unresolved issues including controversy regarding the FDA mandate for the prescription of epinephrine autoinjectors for patients on SLIT; how to approach polysensitized patients; optimal timing and duration of SLIT administration; how to address gaps in therapy; whether antihistamines can prevent local reactions, if certain patient populations (such as persistent asthmatics) should not receive SLIT; and when to instruct patients to self-administer epinephrine. Key points are that physicians should focus on educating patients regarding: (1) when not to administer SLIT; (2) how to recognize a potentially serious allergic reaction to SLIT; and (3) when to administer epinephrine and seek emergency care.