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Background: Uncertainties remain about the molecular mechanisms governing clonal mast cell disorders (CMCD) and anaphylaxis., Objective: This study aims at comparing the burden, phenotype and behavior of mast cells (MCs) and basophils in patients with CMCD with wasp venom anaphylaxis (CMCD/WVA + ), CMCD patients without anaphylaxis (CMCD/ANA - ), patients with an elevated baseline serum tryptase (EBST), patients with wasp venom anaphylaxis without CMCD (WVA + ) and patients with a non-mast cell haematological pathology (NMHP)., Methods: This study included 20 patients with CMCD/WVA + , 24 with CMCD/ANA - , 19 with WVA + , 6 with EBST and 5 with NMHP. We immunophenotyped MCs and basophils and compared baseline serum tryptase (bST) and both total and venom specific IgE in the different groups. For basophil studies, 13 healthy controls were also included., Results: Higher levels of bST were found in CMCD patients with wasp venom anaphylaxis, CMCD patients without anaphylaxis and EBST patients. Total IgE levels were highest in patients with wasp venom anaphylaxis with and without CMCD. Bone marrow MCs of patients with CMCD showed lower CD117 expression and higher expression of CD45, CD203c, CD63, CD300a and FcεRI. Within the CMCD population, patients with wasp venom anaphylaxis showed a higher expression of FcεRI as compared to patients without anaphylaxis. Expression of MRGPRX2 on MCs did not differ between the study populations. Basophils are phenotypically and functionally comparable between the different patient populations., Conclusion: Patients with CMCD show an elevated burden of aberrant activated MCs with a significant overexpression of FcεRI in patients with a wasp venom anaphylaxis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer RMC declared a past co-authorship with the authors DE, MF, AG, MMH, CB, ID, and VS to the handling Editor., (Copyright © 2022 Elst, De Puysseleyr, Ebo, Faber, Van Gasse, van der Poorten, Decuyper, Bridts, Mertens, Van Houdt, Hagendorens, De Clerck, Verlinden, Vermeulen, Maes, Berneman, Valent and Sabato.)

Background: Studies on the mechanisms that govern mast cell (MC) functions are hindered by the difficulties in isolating sufficient numbers of these tissue-resident cells. Therefore, many research groups use cultured human MCs obtained out of progenitor cells. However, these culture methods significantly differ regarding primary source material, culture durations and conditions. Consequently, the finally obtained cells are likely to exhibit morphological, phenotypical and/or functional heterogeneity., Objective: To compare the phenotype and functionality of cells cultured from peripheral blood and bone marrow progenitor cells from patients with suspected clonal MC disease. These cells are designated as PBCMCs and BMCMCs, respectively., Methods: Twenty paired PBCMCs and BMCMCs cultures starting from CD34 + progenitor cells were compared. Cells were cultured for 4 weeks. Phenotyping included Giemsa and CD117 staining and flow cytometric staining for CD117, CD203c, FcεRI, MRGPRX2, CD300a, CD32, CD63 and CD25. Functional assessment included measurement of the up-regulation of CD63 after cross-linking of the high affinity receptor for IgE (FcεRI) with anti-FcεRI and ligation of MRGPRX2 with substance P., Results: PBCMCs and BMCMCs are phenotypically comparable. Functionally, after activation with anti-FcεRI and substance P, PBCMCs and BMCMCs show similar up-regulation of the lysosomal degranulation marker CD63. However, the yield of PBCMCs is higher than BMCMs and peripheral blood cultures are purer than bone marrow cultures., Conclusion: PBCMCs are an attractive alternative to the more difficult to obtain BMCMCs for the exploration of the complex mechanisms that govern IgE- and MRGPRX2-dependent MC activation and degranulation. Unlike BMCMCs, PBCMCs are easily accessible and enable repetitive analyses., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Recent studies show that nsLTP sensitization is not limited to the Mediterranean basin and can present diverse clinical phenotypes. It remains challenging to predict clinical outcome when specific IgE antibodies (sIgE) to nsLTPs are present. This study compares both clinical and in vitro allergy characteristics but also diagnostic performance of a basophil activation test (BAT) and sIgG4 in nsLTP-sensitized patients from Antwerp (ANT, Belgium) and Barcelona (BCN, Spain)., Methods: Adult subjects with positive sIgE rPru p 3 and/or rMal d 3 ≥ 0.10 kU A /L (n = 182) and healthy controls (n = 37) were included. NsLTP-sensitized individuals were stratified according to clinical symptoms with peach/apple, respectively. BAT rPru p 3 and rMal d 3 were performed and sIgG4 antibodies to both components quantified., Results: In BCN, only ratios of sIgG4/sIgE rMal d 3 and BAT rMal d 3 (0.001 µg/mL) can identify clinically relevant Mal d 3 sensitization (sensitivity of 60%-63% and a specificity of 75%-67%, respectively). In ANT, only the sIgE/total IgE rPru p 3 ratio shows added value (sensitivity 60% and specificity 83%). Finally, it appears that symptomatic patients in BCN are more sensitive to lower allergen concentrations compared to ANT. In addition, it was shown that ANT patients were more often sensitized to pollen and that specific pollen sources differed between regions., Conclusions: NsLTP-related allergy profiles and diagnostic performance differ significantly between regions and are component-specific, which makes extrapolation of data difficult to do. In addition, it seems that basophil sensitivity might show geographical differences. Additional research is needed to confirm these findings., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Correct diagnosis of immediate drug hypersensitivity reactions (IDHRs) can pose a significant challenge, mainly because of the absence of reliable in vitro tests, uncertainties associated with skin testing, and incomplete understanding of the underlying mechanisms., Aim: To summarize and hypothesize on the potential of basophil activation test (BAT) as a safe aid to explore the mechanistic endotypes of IDHR, to identify antibody recognition sites, and to monitor drug desensitization., Methods: A literature search was conducted using the keywords "allergy, basophil activation, CD63, CD203c, diagnosis, drugs, hypersensitivity, flow cytometry"; this was complemented by the authors' own expertise., Results: At present BAT has mainly been employed as a diagnostic aid. However, evidence is emerging that the technique might also deepen our insights in immune (allergic) and nonimmune (nonallergic) mechanistic processes of IDHR. It is anticipated that BAT might also benefit the identification of antibody recognition sites and benefit our understandings of desensitization strategies., Conclusion: Although the nondiagnostic application of BAT in IDHR is still in its infancy, with increasing employment, we can expect the technique to become a valuable asset to study many domains of IDHR that remain poorly understood.

The basis of flow cytometric allergy diagnosis is the quantification of changes in the expression of basophilic surface membrane markers (Ebo et al., Clin Exp Allergy 34: 332-339, 2004). Upon encountering specific allergens recognized by surface receptor FcεRI-bound IgE, basophils not only secrete and generate quantifiable bioactive mediators but also upregulate the expression of different markers (e.g., CD63, CD203c) which can be detected by multicolor flow cytometry using specific monoclonal antibodies (Ebo et al., Cytometry B Clin Cytom 74: 201-210, 2008). Here, we describe two flow cytometry-based protocols which allow the detection of surface marker activation (Method 1) and changes in intragranular histamine (Method 2), both reflecting different facets of basophil activation.

Background: Misdiagnosis of amoxicillin (clavulanic acid) (AX(/CL)) hypersensitivity has serious consequences. A drug challenge (DC) is the final diagnostic to affirm or infirm AX(/CL) hypersensitivity. However, uncertainties remain whether a prolonged drug challenge (pDC) should benefit the diagnosis of a nonimmediate AX(/CL) hypersensitivity., Objective: To assess the added value of a standardized 7-day pDC in the diagnosis of nonimmediate or unclear penicillin hypersensitivity., Methods: A total of 132 patients with a history of a nonimmediate hypersensitivity reaction or an unclear reaction to AX(/CL) or an undefined penicillin with a negative diagnostic workup including a single-day DC (DC) with AX(/CL) were selected. In all these patients, an additional pDC with AX(/CL) was planned. Thirteen patients started the pDC immediately after the DC. To ensure that hypersensitivity symptoms manifesting during the pDC course do not result from the DC, in the remaining 119 patients, the pDC was scheduled after a washout of 1 week., Results: A total of 128 patients (12 without washout, 116 with washout) completed the pDC. Three patients reacted with a mild maculopapular exanthema. However, the value of a pDC was evidenced in only 1 patient who reacted during her pDC after an uneventful washout. In 2 patients pDC was cancelled because they reacted during the washout., Conclusions: A pDC is of limited added value to the diagnostic algorithms of nonimmediate hypersensitivity reaction or unclear hypersensitivity reactions to AX(/CL). In our hands, the traditionally recommended diagnostic algorithm that offers a 1-day DC as a final diagnostic in patients with negative workup for AX(/CL) is appropriate., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Despite numerous efforts to describe the clinical manifestations and the epidemiology of perioperative hypersensitivity (POH), there remains room to increase awareness among anesthetists and immunologists/allergists., Objective: To report the findings of a 17-year survey of suspected POH in Antwerp, Belgium., Methods: We analyzed clinical and diagnostic data from 715 patients referred because of a suspected POH reaction, between January 1, 2001, and May 31, 2018. A total of 456 patients demonstrating a POH could be queried about subsequent anesthesia., Results: A total of 608 cases formed the final dataset; 208 had a non-life-threatening reaction and 400 a life-threatening reaction. In life-threatening reactions, hypotension was predominating. In the non-life-threatening reactions, 83.9% of the patients displayed cutaneous manifestations. In life-threatening reactions, intravenous adrenaline and fluids were administered in 75.7% and 31%, respectively, and 41.3% had their intervention abandoned. Mast cell activation (MCA) was mainly, but not exclusively, observed in severe grades but did not predict the mechanistic process nor the culprit. A cause was identified in 77.8% of severe and 48.6% of milder cases. Main culprits were neuromuscular blocking agents, latex, cefazolin, and dyes. A total of 156 cases had uneventful anesthesia, except 1 patient who was inadvertently re-exposed to hidden chlorhexidine., Conclusions: This study highlights that there is room for an improved acute management and an optimized diagnostic workup that should not be restricted to patients with severe reactions and/or showing MCA., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The neuromuscular blocking agent (NMBA) rocuronium is a relevant cause of perioperative hypersensitivity (POH) with a significant risk of diagnostic error. Recently, it has been suggested to reclassify hypersensitivity to NMBA as type A reactions resulting from off-target occupation of the nonimmune MRGPRX2 receptor., Objective: To investigate whether basophil activation experiments can benefit diagnosis and add to the insights in the pathomechanisms of rocuronium hypersensitivity., Methods: A total of 140 patients with a suspected POH to rocuronium in whom peak tryptase was available had complete diagnostic workup for all potential culprits including triple confirmatory testing with skin tests, basophil activation test (BAT), and quantification of specific IgE (sIgE) antibodies to rocuronium and morphine. To further analyze the clinical relevance of sIgE antibodies, quantitative basophil inhibition experiments were performed by coincubation of the cells with rocuronium and morphine, an opiate known to harbor a substituted ammonium structure., Results: Diagnosis of rocuronium hypersensitivity was established in 72 of 140 patients (51.4%), of whom 65 (90.3%) demonstrated mast cell activation. Of the 72 patients, 64 displayed a positive skin test, 8 (11.1%) had their diagnosis documented only by BAT. Coincubation of morphine and rocuronium induced a dose-dependent inhibition of BAT with rocuronium that was restricted to 4 of 6 patients with IgE reactivity to rocuronium and/or morphine., Conclusions: BAT can benefit diagnosis of rocuronium hypersensitivity. As basophils barely express MRGPRX2 and BAT rocuronium can be inhibited by morphine, we believe that hypersensitivity to rocuronium still mainly results from IgE/high-affinity receptor for sIgE (FcεRI)-dependent effector cell activation. However, it cannot be excluded that in a few patients rocuronium hypersensitivity results from off-target occupation of the MRGPRX2 receptor., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Cannabis allergy (CA) has mainly been attributed to Can s 3, the nonspecific lipid transfer protein (nsLTP) of Cannabis sativa. Nevertheless, standardized diagnostic tests are lacking and research on CA is scarce., Objective: To explore the performance of 5 cannabis diagnostic tests and the phenotypic profile of CA., Methods: A total of 120 patients with CA were included and stratified according to the nature of their cannabis-related symptoms; 62 healthy and 189 atopic controls were included. Specific IgE (sIgE) hemp, sIgE and basophil activation test (BAT) with a recombinant Can s 3 protein from Cannabis sativa (rCan s 3), BAT with a crude cannabis extract, and a skin prick test (SPT) with an nCan s 3-rich cannabis extract were performed. Clinical information was based on patient history and a standardized questionnaire., Results: First, up to 72% of CA reporting likely-anaphylaxis (CA-A) are Can s 3 sensitized. Actually, the Can s 3-based diagnostic tests show the best combination of positive and negative predictive values, 80% and 60%, respectively. sIgE hemp displays 82% sensitivity but only 32% specificity. Secondly, Can s 3+CA reported significantly more cofactor-mediated reactions and displayed significantly more sensitizations to other nsLTPs than Can s 3-CA. Finally, the highest prevalence of systemic reactions to plant-derived foods was seen in CA-A, namely 72%., Conclusions: The most effective and practical tests to confirm CA are the SPT with an nCan s 3-rich extract and the sIgE rCan s 3. Can s 3 sensitization entails a risk of systemic reactions to plant-derived foods and cofactor-mediated reactions. However, as Can s 3 sensitization is not absolute, other cannabis allergens probably play a role., (Copyright © 2018. Published by Elsevier Inc.)

Secondary food allergies due to cross-reactivity between inhalant and food allergens are a significant and increasing global health issue. Cross-reactive food allergies predominantly involve plant-derived foods resulting from a prior sensitization to cross-reactive components present in pollen (grass, tree, weeds) and natural rubber latex. Also, primary sensitization to allergens present in fungi, insects, and both nonmammalian and mammalian meat might induce cross-reactive food allergic syndromes. Correct diagnosis of these associated food allergies is not always straightforward and can pose a difficult challenge. As a matter of fact, cross-reactive allergens might hamper food allergy diagnosis, as they can cause clinically irrelevant positive tests to cross-reacting foods that are safely consumed. This review summarizes the most relevant cross-reactivity syndromes between inhalant and food allergens. Particular focus is paid to the potential and limitations of confirmatory testing such as skin testing, specific IgE assays, molecular diagnosis, and basophil activation test., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Quantification of specific IgE (sIgE) antibodies constitutes an important measure to document anesthesia-related immediate hypersensitivity reactions (IHRs). However, only a few drug-specific assays are available and their predictive value is not known. In cases of non-IgE mediated IHRs, diagnosis might benefit from cellular tests such as basophil mediator release tests and basophil activation tests (BATs). To review the potential and limitations of quantification of sIgE, mediator release, and BAT in anesthesia-related IHRs, a literature search was conducted using the key words allergy, basophil activation, CD63, CD203c, diagnosis, drugs, hypersensitivity, flow cytometry, MRGPRX2, specific IgE antibodies, leukotrienes, histamine, and tryptase; this was complemented by the authors' experience. The drugs and compounds that have predominantly been studied are neuromuscular blocking agents (NMBAs), β-lactams, latex, and chlorhexidine. For sIgE NMBA, sensitivity and specificity varies between 38.5% to 92% and 92% to 100%, respectively. For sIgE β-lactams, sensitivity varies between 0% to 85% and specificity between 52% to 100%. sIgE to morphine should not be used in isolation to diagnose IHRs to NMBAs or opiates. sIgE for latex, and, in difficult cases, molecular diagnosis with quantification of sIgE to Hevea components constitute reliable diagnostics. For drugs, the sensitivity of BAT varies between 50% and 60% and specificity reaches 80% to 90%. Basophil mediator release tests seem to be abandoned and supplanted by BATs., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Mechanisms that govern priming and degranulation of human mast cells (MCs) remain elusive. Besides, most of our knowledge is based on experiments from which data only reflect an average of all stimulated cells. This study aims at investigating the effects of proinflammatory cytokines IL-6, IL-33, and TNF-α on IgE-dependent and IgE-independent activation of individual MCs., Methods: MCs were derived from CD34 + progenitors isolated from 50 mL whole blood from 4 healthy controls and 5 birch pollen allergic patients. Passively sensitized MCs were preincubated with IL-6, IL-33, or TNF-α and stimulated with anti-IgE/birch pollen allergen or substance P, the latter being a ligand for the G-protein-coupled MRGPRX2-receptor. Activation-i.e., upregulation of CD203c-and anaphylactic degranulation-i.e., appearance of CD63-were measured using flow cytometry., Results: Preincubation with IL-33 demonstrated upregulated CD203c density without degranulation. Subsequent IgE-dependent stimulation (anti-IgE/birch pollen allergen) resulted in higher appearance of CD63 as compared to cells without preincubation, indicating IL-33 to exert a priming effect (P = 0.04). IL-6 only increased allergen-specific responses but to a lesser extent than IL-33. Combination of IL-33/IL-6 had a synergistic effect, demonstrating more degranulation in response to allergen. TNF-α had no effect on IgE-mediated activation, nor synergistic effects with IL-33. Stimulation with substance P resulted in degranulation that could not be enhanced by preincubation., Conclusions: In conclusion, IL-33, and in a lesser extent IL-6, prime individual MCs for subsequent IgE-mediated activation. Moreover, this priming effect is synergistic. In contrast, none of the cytokines had a priming effect on MRGPRX2-mediated activation of MCs. © 2017 International Clinical Cytometry Society., (© 2017 International Clinical Cytometry Society.)

Immediate drug hypersensitivity reactions (IDHR) to moxifloxacin constitute a pathomechanistic conundrum and a diagnostic challenge. Our objective was to study whether simultaneous phenotyping and quantification of histamine release might add to our knowledge about the basophil activation properties of moxifloxacin and constitute a reliable diagnostic aid. Fifteen patients with an IDHR to moxifloxacin and nine moxifloxacin challenged controls were selected. All had a basophil activation test (BAT) with moxifloxacin. Flow cytometric analysis of basophil responses implied labeling for CD63, CD203c, and intracellular histamine. Unlike tolerant challenged controls, basophilic upregulation of CD203c in response to moxifloxacin was observed in seven of 15 patients. Only two of these seven patients demonstrated appearance of CD63 and release of histamine. In the remainder eight patients, no basophil responses were demonstrable. In conclusion, immediate hypersensitivity to moxifloxacin might involve mechanisms difficult to capture by traditional CD63-/CD203c-based BAT. Deciphering the complexity of quinolone IDHR seems mandatory., (© 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: For most physicians, quantification of drug-specific immunoglobulin E (drug-sIgE) antibodies constitutes the primary in vitro measure to document immediate drug hypersensitivity reactions (IDHR). Unfortunately, this is often insufficient to correctly identify patients with IgE-mediated IDHR and impossible for non-IgE-mediated IDHR that result from alternative routes of basophil and mast cell activation. In these difficult cases, diagnosis might benefit from cellular tests such as basophil activation tests (BAT)., Aim: The aim was to review the potential and limitations of quantification of sIgE and BAT in diagnosing IDHR. The utility of quantification of serum tryptase is discussed., Methods: A literature search was conducted using the key words allergy, basophil activation, CD63, CD203c, diagnosis, drugs, hypersensitivity, flow cytometry, specific IgE antibodies; this was complemented by the authors' own experience., Results: The drugs that have been most studied with both techniques are β-lactam antibiotics and curarizing neuromuscular blocking agents (NMBA). For sIgE morphine, data are available on the value of this test as a biomarker for sensitization to substituted ammonium structures that constitute the major epitope of NMBA, especially rocuronium and suxamethonium. For the BAT, there are also data on non-steroidal anti-inflammatory drugs (NSAIDs) and iodinated radiocontrast media. For β-lactam antibiotics, sensitivity and specificity of sIgE varies between 0 and 85% and 52 and 100%, respectively. For NMBA, sensitivity and specificity varies between 38.5 and 92% and 85.7 and 100%, respectively. Specific IgE to morphine should not be used in isolation to diagnose IDHR to NMBA nor opiates. For the BAT, sensitivity generally varies between 50 and 60%, whereas specificity attains 80%, except for quinolones and NSAIDs., Conclusions: Although drug-sIgE assays and BAT can provide useful information in the diagnosis of IDHR, their predictive value is not absolute. Large-scale collaborative studies are mandatory to harmonize and optimize test protocols and to establish drug-specific decision thresholds.

Background: For many physicians, quantification of serum drug-specific IgE (sIgE) antibodies constitutes the first measure in the diagnostic approach of immediate drug hypersensitivity reactions (IDHR)., Aim: To review the accuracy and limitations of the main drug-sIgE tests, especially those that are commercially available., Methods: A literature search was conducted, using the key-words allergy, diagnosis, drugs, hypersensitivity, specific IgE antibodies; this was complemented by the authors' own experience., Results: The drugs that have mostly been studied appeared to be β-lactam antibiotics, neuromuscular blocking agents (NMBA) and morphine, the latter as a biomarker for sensitisation to substituted ammonium structures that constitute the major epitope of NMBA. For β-lactams sensitivity and specificity varied between 0-85% and 52-100%, respectively. For NMBA, sensitivity and specificity varied between 38.5-92% and 92-100%, respectively. With respect to sIgE to morphine it appears this drug to be a sensitive biomarker for sensitisation to rocuronium and suxamethonium but not for atracurium. However, sIgE morphine should not be applied in isolation to diagnose IDHR to NMBA nor opiates., Conclusions: Although drug-sIgE assay can provide valuable information they should not be performed in isolation to establish correct diagnosis, as their predictive value is not per se absolute. Larger comprehensive studies are urgently required to determine the accuracy of drug-sIgE assays., (Copyright © 2016. Published by Elsevier B.V.)

Histamine and its release can be studied by multicolor flow cytometry on a single cell level by an enzyme affinity method (HistaFlow®). However, for the time-being, the clinical and scientific application of the HistaFlow® technique remains limited. This study aims at verifying the reliability of the HistaFlow® as an instrument to quantify IgE-mediated basophil responses to drugs, i.e., rocuronium, which are believed to be less potent basophil activators than large proteinaceous allergens. Ten patients and three exposed control individuals were included in this study. Each subject underwent in vitro basophil activation tests (HistaFlow®) with 0.16 and 1.6 mmol/L rocuronium. Patients showed an activation of basophils ranging from 11 to 86% of CD63 positive basophils and a median histamine release per cell from 68 to 100% after stimulation with an optimal concentration of 1.6 mmol/L rocuronium. For the control individuals no activation was demonstrable. This study confirms that the HistaFlow® technique is a reliable tool to study histamine release by individual cells in response to drugs. Although the HistaFlow® technique will probably not add to the diagnostic management of rocuronium allergy, our findings suggest that the technique could constitute an important asset for future studies on the pathomechanism(s) of immediate drug hypersensitivity reactions. © 2015 International Clinical Cytometry Society., (© 2015 International Clinical Cytometry Society.)

In rheumatoid arthritis (RA) patients, weekly intake of methotrexate (MTX) is the basic drug treatment. This observational study aims to investigate how many RA patients are adherent in terms of MTX intake and to identify determinants of non-adherence. Intake of MTX (orally or via injection) was recorded in 129 RA patients with an electronic monitoring system (MEMS(®)) during 16 weeks. In addition, two adherence questionnaires, the Medication Adherence Report Scale (MARS-5) and the Compliance-Questionnaire-Rheumatology (CQR) as well as a visual analogue scale (VAS) measuring MTX adherence, were administered to these patients. As possible determinants of adherence, data on demographics, disease and treatment characteristics, depression, illness cognitions, motivation, and social support were collected. Of all participants, 58 % were fully adherent and 75 % skipped at most one dose during 16 weeks. A better mental health status and suffering from comorbidities had a positive effect on adherence, while living alone had a negative effect. These three predictors explained 30 % of the variance in MTX adherence. Of the three self-report medication adherence measures, the VAS correlated the highest with the results of the electronic monitoring system (r = 0.552, p = 0.01). A relatively high adherence rate was observed in RA patients treated with MTX. The determinants identified by this study could be used to screen patients at risk for non-adherence. A simple VAS scale seems to be an acceptable way for a preliminary screening of MTX adherence.

Objectives: Peanut allergy shows distinct clinical patterns that can be predicted by component resolved diagnosis. However, data about peanut sensitization profiles in populations with a broad age stratification are scarce., Methods: Sera of 89 peanut allergic patients (age 1-70 years), 21 infants (<1 year) with atopic dermatitis (AD) sensitized to peanut, 24 age matched peanut-tolerant individuals with positive specific IgE (sIgE) to peanut and 15 healthy individuals were tested for sIgE reactivity to rAra h 1, rAra h 2, rAra h 3, rAra h 8, rAra h 9 and rBet v 1 (FEIA ImmunoCAP, Thermo Fisher Scientific)., Results: In infants with AD, Ara h 1, Ara h 2 and Ara h 3 enabled to explain 14/21 (67%) of peanut sensitizations. No sensitization to Ara h 8 or Bet v 1 was observed. Patients with generalized reactions were more frequently sensitized to Ara h 1, Ara h 2 and Ara h 3 compared to patients with an oral allergy syndrome (OAS) and peanut-tolerant patients. Sensitization to Ara h 8 was significantly more observed in patients with an OAS. Ara h 2 showed to be the best marker to distinguish patients with generalized reactions from patients with an OAS and/or peanut sensitized patients but tolerating the legume., Conclusion: Sensitization to Ara h 1, Ara h 2 and Ara h 3 can have an early onset and is predominantly associated with a more severe outcome. Ara h 2 is the best marker of a generalized peanut allergy.