Assessing delayed penicillin hypersensitivity using the PENFAST+ score

IntroductionApproximately 10% of individuals report a suspected allergy to penicillin, but according to allergy work-ups, only 10%–15% of them are truly allergic. A clinical decision score, the PEN-FAST, was developed and validated to identify adults with low-risk penicillin allergy.ObjectivesThe objective of this study was to improve the performance of the PEN-FAST score, particularly for those with delayed hypersensitivity (HS), by improving the negative predictive value.MethodsSTEP 1: Retrospective evaluation of the PEN-FAST score in patients with proven immediate and delayed penicillin allergy. STEP 2: Identification of additional criteria among Step 1 patients misclassified by PEN-FAST score. Development of the PEN-FAST+ score using multivariable logistic regression in a prospective cohort of patients with a suspicion of HS to penicillin. STEP 3: Comparison of diagnostic performances of PEN-FAST and PEN-FAST+ scores.ResultsThe PEN-FAST score showed limitations in predicting the relapse of immediate skin HS or delayed maculopapular exanthema, with 28.6% and 38.4% of patients misclassified, respectively. We identified two potential additional criteria: skin rash lasting more than 7 days and immediate reaction occurring in less than 1 h (generalized or localized on palmoplantar area or scalp itching/heat feeling). A total of 32/252 (12.7%) patients were confirmed to be allergic to penicillin. With PEN-FAST, 37% of patients (n = 10) with delayed allergic penicillin HS were misclassified. With PEN-FAST+, 3 patients with delayed HS confirmed by a ST (11.1%) were misclassified. The AUC was significantly higher for PEN-FAST+ than PEN-FAST (85% vs. 72%, p = 0.03)

Associations of airway inflammation and responsiveness markers in non asthmatic subjects at start of apprenticeship

<p>Abstract</p> <p>Background</p> <p>Bronchial Hyperresponsiveness (BHR) is considered a hallmark of asthma. Other methods are helpful in epidemiological respiratory health studies including Fractional Exhaled Nitric Oxide (FENO) and Eosinophils Percentage (EP) in nasal lavage fluid measuring markers for airway inflammation along with the Forced Oscillatory Technique measuring Airway resistance (AR). Can their outcomes discriminate profiles of respiratory health in healthy subjects starting apprenticeship in occupations with a risk of asthma?</p> <p>Methods</p> <p>Rhinoconjunctivitis, asthma-like symptoms, FEV1 and AR post-Methacholine Bronchial Challenge (MBC) test results, FENO measurements and EP were all investigated in apprentice bakers, pastry-makers and hairdressers not suffering from asthma. Multiple Correspondence Analysis (MCA) was simultaneously conducted in relation to these groups and this generated a synthetic partition (EI). Associations between groups of subjects based on BHR and EI respectively, as well as risk factors, symptoms and investigations were also assessed.</p> <p>Results</p> <p>Among the 441 apprentice subjects, 45 (10%) declared rhinoconjunctivitis-like symptoms, 18 (4%) declared asthma-like symptoms and 26 (6%) suffered from BHR. The mean increase in AR post-MBC test was 21% (sd = 20.8%). The median of FENO values was 12.6 ppb (2.6-132 range). Twenty-six subjects (6.7%) had EP exceeding 14%. BHR was associated with atopy (p < 0.01) and highest FENO values (p = 0.09). EI identified 39 subjects with eosinophilic inflammation (highest values of FENO and eosinophils), which was associated with BHR and atopy.</p> <p>Conclusions</p> <p>Are any of the identified markers predictive of increased inflammatory responsiveness or of development of symptoms caused by occupational exposures? Analysis of population follow-up will attempt to answer this question.</p

COVID-19 vaccination in patients receiving allergen immunotherapy (AIT) or biologicals:EAACI recommendations

Immune modulation is a key therapeutic approach for allergic diseases, asthma and autoimmunity. It can be achieved in an antigen-specific manner via allergen immunotherapy (AIT) or in an endotype-driven approach using biologicals that target the major pathways of the type 2 (T2) immune response: immunoglobulin (Ig)E, interleukin (IL)-5 and IL-4/IL-13 or non-type 2 response: anti-cytokine antibodies and B-cell depletion via anti-CD20. Coronavirus disease 2019 (COVID-19) vaccination provides an excellent opportunity to tackle the global pandemics and is currently being applied in an accelerated rhythm worldwide. The vaccine exerts its effects through immune modulation, induces and amplifies the response against the severe acute respiratory syndrome coronavirus (SARS-CoV-2). Thus, as there may be a discernible interference between these treatment modalities, recommendations on how they should be applied in sequence are expected. The European Academy of Allergy and Clinical Immunology (EAACI) assembled an expert panel under its Research and Outreach Committee (ROC). This expert panel evaluated the evidence and have formulated recommendations on the administration of COVID-19 vaccine in patients with allergic diseases and asthma receiving AIT or biologicals. The panel also formulated recommendations for COVID-19 vaccine in association with biologicals targeting the type 1 or type 3 immune response. In formulating recommendations, the panel evaluated the mechanisms of COVID-19 infection, of COVID-19 vaccine, of AIT and of biologicals and considered the data published for other anti-infectious vaccines administered concurrently with AIT or biologicals

Physiopathologie et explorations des toxidermies immunoallergiques

Non disponible / Not availableLes toxidermies immuno-allergiques constituent un important problème de santé publique mais sont de physiopathologie mal connue. Ce travail est consacré à la définition et à l'exploration de ces pathologies, dans l'optique d'une amélioration de la prise en charge diagnostique des toxidermies et d'une meilleure compréhension des anomalies immunitaires impliquées dans leur apparition . Sur la base d'une ri goureuse méthodologie clinique, une population de 310 patients, inclus de façon prospective, a été étudiée, et trois axes d'étude ont étédéveloppés: appréciation de la valeur des tests cutanés en fonction de la sémiologie et du médicament responsable, exploration des cellules et molécules immunocompétentes potentiellement impliquées in situ, évaluation des réponses obtenues in vitro à partir des cellules circulantes. Nous avons démontré l' utilité (72% des patients ayant un test cutané positif) et la faisabilité des tests cutanés dans le bilan étiologique des toxidermies, 43% des patients ayant un test épicutané positif (dont 59,3% des sujets ayant développé un exanthème maculopapuleux),24% un prick test positif e l. 66,6% une IDR positive en lecture immédiate et/ou retardée. Ces résultats indiquent que la positivité des tests dépend du médicament en cause, de la sémiologie et donc du mécanismeimmunologique de la toxidermie. Ceci est confirmé par l'immunophénotypage comparatif de biopsies de toxidermies et de tests cutanés lTI t cticamenteux positifs. La plupart des toxidermies lion urticariennes relèventainsi de mécanismes d'hypersensibilité cellulaire retardée impliquant des lymphocytes T. On y observeégalement des cellules denciritiques dermiques CDI a+, et l'expression de molécules d 'adhésion par les cellules dermiques et épidermiques. Nous avons par ailleurs mis en évidence l'expression inattendue de sélectines(CD62L, CD62P) par les kératinocytes. Dans les toxidermies non épidermolytiques nous avons démontré qu'il n'existait pas de phénomènes majeurs d 'apoptose des kératinocytes ou des cellulesT. De plus ces dernières ne semblent pas résulter d'une prolifération clonale in situ comme le montre l'étude du réarrangement du récepteurT pour l'antigène des lymphocytescutanés. L'étude de 17 patients ayant présenté un accident cutané lors de vaccination démontre que les causes de ces toxidermies sont variées : sensibilisation à un des constituant de lasolution vaccinale, complexes immuns circulants ou mécanismes peut-être non immunitaires. Enfin sur des toxidermies variées dans leur sémiologie et leur cause, nous avons évalué l'apport potentiel d'explorations ex vivo à partir de prélèvements sanguins des patients. En conclusion, nos résultats apportent des éléments importants évaluant les critères nécessaires au diagnostic précis de ces accidents médicamenteux et améliorant la compréhension de leurs mécanismes physiopathologiques