Management of Beta-Lactam Antibiotics Allergy: A Real-Life Study.

Beta-lactam allergy is a common problem in everyday medical practice and is recognized as a major public health issue. Carrying this label frequently leads to the avoidance of all beta-lactam antibiotics, favoring the use of other less preferred classes of antibiotics, that are more expensive and associated with more side effects and increased antimicrobial resistance. Therefore, delabeling a beta-lactam allergy is part of antimicrobial stewardship programs. Herein, we retrospectively examined the clinical records of 576 patients who were referred to our center for a label of allergy to beta-lactam antibiotics and were systematically investigated following a standardized algorithm. Our main aim was to evaluate the frequency of confirmed immediate- and delayed-type allergy to commonly prescribed subclasses of beta-lactam antibiotics (penicillin and cephalosporin), as well as the negative predictive value (NPV) and the sensitivity of skin tests. Our secondary aims were to examine the safety of beta-lactam skin testing and drug challenge. We identified that 260 patients reported a history of immediate reactions, 131 of delayed reactions, and 114 of unknown timing or mechanism of reactions. Following assessment and testing, 86 (18.3%) patients had a confirmed allergy to any beta-lactam antibiotics; 63 (13.4%) with an immediate- and 23 (4.9%) with a delayed-type reaction. Most frequently identified confirmed allergy was to penicillins (65 patients), followed by cephalosporins (21 patients). When immediate-type reactions were examined, NPV of skin tests were 96.3% and 100% for penicillins and cephalosporins, respectively. When delayed reactions were considered, NPV were 91.9 and 87.5% for penicillins and cephalosporins, respectively. Evaluation of the safety of skin tests according to the standardized procedure showed that systemic allergic reactions occurred in only 0.7% of skin tests and in 3.1% of drug challenges. Overall, our data indicate that only 18.3% of patients with a beta-lactam allergy label have a confirmed allergy and non-allergic patients can be safely delabeled through allergic workup based on skin tests and drug challenge. This approach supports the policy of saving second-line antibiotics through a standardized allergy workup.

Novel Nanofluidic IgE Assay versus a Reference Method: A Real-World Comparison.

BACKGROUND: Clinically meaningful specific IgE determination is an important step in the diagnosis of allergic diseases. While patient's history and skin prick tests are available during the medical visit, most IgE immunoassays require hours to several days to be available. Recent developments in the field of nanofluidic technology open new horizons for point-of-care management of this unmet medical need. OBJECTIVE: This study aimed to compare IgE diagnostic agreement between a nanofluidic assay (abioSCOPE®) and a laboratory reference method (Phadia Laboratory System®) in a real-world clinical setting. METHODS: Sera from 105 patients whose routine allergy diagnostic workup required a blood sampling were used to compare the novel nanofluidic IgE assay to a reference method in a blind manner for a panel of five respiratory allergens. To assess the agreement between methods, patient records were reviewed by four independent experts to establish the final diagnosis. Experts were blinded to the IgE serological method used, but had access to patient history, skin prick tests, and blood test results. RESULTS: Analytic agreement between the two methods was 81% for the tested panel of allergens (ranging from 77 to 89%). The overall agreement in clinical diagnosis decision taken by the expert panel was 94.6% with the nanofluidic IgE assay when compared to the reference method. CONCLUSION: The nanofluidic IgE assay, as determined through an evaluation based on clinical history, skin prick tests, and IgE measurement, is a valuable tool for allergy experts to identify patients' sensitization patterns at the point of care, and for routine IgE diagnostic workup.

[Food-dependent exercise-induced anaphylaxis : a stepwise diagnosis]. / Anaphylaxie alimentaire à l'effort : un diagnostic par étapes.

Food-dependent exercise-induced anaphylaxis (FDEIA) is a potentially severe food allergy. Physical exercise, NSAID, alcohol, infectious diseases and estrogens are recognized cofactors, able to reduce the amount of allergen needed to achieve a threshold for the induction of anaphylaxis. Various kinds of causative food but only a few responsible proteins have been identified. The best known is wheat ω5-gliadine. An oral food challenge remains the gold standard to prove the diagnosis. Its clinical application remains difficult and includes an allergen challenge, a cofactor challenge and a third step which integrates both of them in a single test. Gluten flour and NSAID + alcohol combination seem more efficient than respectively wheat flour and physical exercise in a provocation test condition.

L'anaphylaxie alimentaire à l'effort est une allergie alimentaire potentiellement sévère. L'exercice physique, les AINS, l'alcool, les infections et les œstrogènes sont des cofacteurs reconnus, capables de diminuer la quantité d'allergènes nécessaire à l'atteinte d'un seuil anaphylactique. Si le panel d'aliments incriminés est large, seules quelques protéines responsables ont été à ce jour identifiées. La plus connue est l'ω5-gliadine du blé. En cas d'incertitude diagnostique, un test de provocation est indiqué. Son application clinique reste difficile et inclut de tester l'allergène de manière isolée et le cofacteur puis d'intégrer les deux dans un même test. La farine de gluten et la combinaison AINS + alcool ont une sensibilité supérieure respectivement à la farine de blé et à l'exercice physique en situation de provocation.

[Innovations in the treatment of severe asthma]. / Allergologie-immunologie clinique. Nouveautés dans le traitement de l'asthme sévère.

In severe asthma, there is a real need for new effective therapies offering a good safety and tolerance profile. Mepolizumab is a humanized anti-interleukin-5 monoclonal antibody, available in Switzerland since 2016 for treatment of severe adult eosinophilic asthma. Other monoclonal antibodies, such as dupilumab, are being developed in the field of asthma.

Dans l'asthme sévère, il existe un réel besoin de nouvelles thérapies efficaces offrant de bons profils de sécurité et de tolérance. Le mépolizumab est un anticorps monoclonal humanisé dirigé contre l'interleukine 5, disponible en Suisse depuis 2016 pour le traitement de l'asthme éosinophilique sévère de l'adulte. D'autres anticorps monoclonaux, comme le dupilumab, un anti-IL-4R, sont actuellement en cours de développement dans cette indication.

Tocilizumab for giant cell arteritis with corticosteroid-resistant progressive anterior ischemic optic neuropathy.

BACKGROUND: Giant cell arteritis is an inflammatory disorder of the medium- and large-size arteries. Permanent visual loss related to arteritic anterior ischemic optic neuropathy is among the most serious complications of this disease and initial treatment usually consists of high dose corticosteroids. There is no consensus in the literature concerning the optimal therapeutic approach in giant cell arteritis patients with corticosteroid-resistant arteritic anterior ischemic optic neuropathy. CASE REPORT: A 73-year-old Caucasian female with biopsy-proven giant cell arteritis developed an acute visual loss of the right eye due to arteritic anterior ischemic optic neuropathy. Despite 5 daily methylprednisolone pulses, systemic symptoms persisted and rapid involvement of the controlateral eye was documented. Therefore, tocilizumab (humanised monoclonal antibody binding the human interleukin-6 receptor) was introduced as a potential salvage therapy with a swift consecutive resolution of the systemic symptoms and stabilization of the ophthalmic lesions. CONCLUSIONS: Although a late effect of steroids pulses cannot be formally ruled out in this dramatic situation, tocilizumab likely offered a decisive effect in preventing bilateral blindness and may have contributed to steroid tapering. Tocilizumab may represent a new early effective second-line treatment option in corticosteroid-resistant anterior ischemic optic neuropathy. More data are needed to confirm this observation and to evaluate the safety profile of this treatment.

[Cardiac sarcoidosis: seven keypoints to remind in order to avoid misdiagnosis]. / Sarcoïdose cardiaque: sept points à rappeler pour ne pas manquer le diagnostic.

Early diagnosis of cardiac sarcoidosis remains difficult in the absence of specific symptoms. The evolution and prognosis of the disease are strongly correlated to an early and appropriate treatment. The multi-modality assessment based on cardiac MRI and positron emission tomography associated with computed tomography (PET/CT) has significantly improved the detection of cardiac sarcoidosis over the last two decades. These approaches appear as useful and suitable imaging strategy for the early diagnosis, the assessment of the disease extent as well as the management and therapeutic follow-up. This article is a didactic review on cardiac sarcoidosis, with a special focus on recent diagnostic and therapeutic modalities, prognosis and interest of imaging techniques.

Exhaustion of bacteria-specific CD4 T cells and microbial translocation in common variable immunodeficiency disorders.

In the present study, we have investigated the functional profile of CD4 T cells from patients with common variable immunodeficiency (CVID), including production of cytokines and proliferation in response to bacteria and virus-derived antigens. We show that the functional impairment of CD4 T cells, including the reduced capacity to proliferate and to produce IFN-γ and IL-2, was restricted to bacteria-specific and not virus-specific CD4 T cells. High levels of endotoxins were found in the plasma of patients with CVID, suggesting that CD4 T cell dysfunction might be caused by bacterial translocation. Of note, endotoxemia was associated with significantly higher expression of programmed death 1 (PD-1) on CD4 T cells. The blockade of the PD-1-PD-L1/2 axis in vitro restored CD4 T cell proliferation capacity, thus indicating that PD-1 signaling negatively regulates CD4 T cell functions. Finally, we showed that intravenous immunoglobulin G (IVIG) treatment significantly reduced endotoxemia and the percentage of PD-1(+) CD4 T cells, and restored bacteria-specific CD4 T cell cytokine production and proliferation. In conclusion, the present study demonstrates that the CD4 T cell exhaustion and functional impairment observed in CVID patients is associated with bacterial translocation and that IVIG treatment resolves bacterial translocation and restores CD4 T cell functions.

[Severe delayed drug hypersensitivity reactions]. / Formes sévères d'hypersensibilité médicamenteuse retardée.

Although most delayed drug hypersensitivity reactions are mild and show rapid improvement after drug discontinuation, there are severe systemic and/or cutaneous drug reactions which may be life-threatening. These entities are discussed here, namely DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms), acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN). Early detection of warning signs and symptoms may help to take appropriate measures precociously.

Acute right and left heart failure caused by an intrathoracic stomach.

Hiatus hernia (HH) is a frequent condition and is asymptomatic most of the time. Common symptoms can include epigastric pain, postprandial fullness, and nausea. We report a case of postprandial acute right and left heart failure caused by an intrathoracic stomach in a previously asymptomatic woman. Clinical manifestations included acute pulmonary edema and severe hypotension after administration of vasodilators for treatment of acute left heart failure. Chest computed tomography images showed a pre- and afterload compromise caused by a large compressive HH with massive gastric distension. To the best of our knowledge, ours is the first report of both acute right and left heart failure due to an HH. The prompt placement of a nasogastric tube was lifesaving. We believe that the diagnosis of HH ought to be taken into consideration by emergency physicians and included in the differential diagnosis for acute postprandial heart failure.