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Very few studies have investigated whether unilateral choanal atresia is associated with permanent olfactory deficits. This study aimed to evaluate the olfactory performance of patients with unilateral choanal atresia postsurgically. Three patients with unilateral atresia were examined in terms of olfactory performance with the Sniffin' Sticks test (odor identification, threshold, and discrimination), size of the olfactory bulb, and volumetric brain changes. All patients demonstrated significantly lower olfactory performance in terms of odor threshold on the same side with the choanal atresia. Grey matter reductions were found ipsilaterally in the hippocampus. This pilot study indicates that persistent olfactory deficits and volumetric brain changes are present in patients with unilateral choanal atresia.

No abstract available

L’allergie alimentaire est une pathologie fréquente. Sa forme la plus sévère, l’anaphylaxie alimentaire, est potentiellement fatale. Cette étude rétrospective a analysé les anaphylaxies alimentaires de grade > 2 qui ont fait l’objet d’un bilan allergologique chez le même spécialiste aux Cliniques universitaires Saint-Luc entre 2017 et 2019. La population étudiée était principalement adulte (âge moyen de 33,7 ans). Les anaphylaxies étaient majoritairement causées par des allergènes à déclaration obligatoire. Le bilan allergologique reposait sur une anamnèse détaillée, la mise en évidence d’une sensibilisation (in vivo et/ou in vitro), et dans certains cas la réalisation d’un test de provocation par voie orale. Les crustacés et l’arachide représentaient plus d’un tiers des aliments en cause (38,7%). De l’adrénaline intramusculaire a été administrée dans moins de la moitié des anaphylaxies. La prise en charge immédiate de l’anaphylaxie alimentaire est encore trop souvent inadéquate en regard des recommandations internationales.

Les compléments alimentaires à base de produits de la ruche sont plébiscités par les consommateurs. Cependant, ils ne sont pas dénués de risque allergique pour les patients atopiques, comme le souligne l’avis rendu par l’ANSES en 2018. Nous présentons l’étude rétrospective descriptive des cas d’anaphylaxie alimentaire aux pollens en pelote et autres produits apicoles déclarés au Réseau d’Allergo-Vigilance® de 2002 à juin 2021. Résultats. – Au total, 32 cas d’anaphylaxie ont été déclarés, soit 1,26 % de la totalité des déclarations d’anaphylaxie alimentaire, dont 16 cas au pollen en pelote (50 %), 14 au miel (40,6 %), 2 à la gelée royale (6,3 %) et 1 à la propolis (3,1 %). Il s’agit principalement d’adultes (81,3 %), avec la moitié de réactions anaphylactiques de grade 2 et un tiers de grade 3. Les 2 cas d’anaphylaxie à la gelée royale étaient de grade 3 avec de l’asthme. Une hospitalisation/surveillance a été réalisée chez 37,5 % des patients, seule- ment 21,9 % ont bénéficié d’un traitement par adrénaline. Une sensibilisation pollinique était retrouvée dans 87,5 % des cas et 53,2 % avaient une rhinite saisonnière. Dans l’anaphylaxie au pollen en pelote, tous les patients (100 %) étaient sensibilisés à des pollens, dont 75 % à ceux des composées. Concernant l’anaphylaxie au miel, seuls 3 patients ne présentaient pas de sensibilisation aux pollens. Conclusions. – Il s’agit de la plus grande série rapportée d’anaphylaxie aux produits de la ruche. L’allergie alimentaire au pollen en pelote est liée le plus souvent à la présence de pollens de composées (pollens entomophiles mais aussi anémophiles), de même que pour l’allergie au miel, avec cependant la possibilité d’un lien avec des protéines de sécrétions apiaires comme MRJP1, qui est l’allergène incriminé dans l’anaphylaxie à la gelée royale.

Background: The literature describes several risk factors for hypersensitivity (HS) reactions to iodinated contrast media (ICM). Objective: To analyze the characteristics of patients experiencing HS reactions to ICM with a focus on oncological status. Methods: All patients (n=80) with suspected HS to ICM who underwent an allergy evaluation in a Belgian University Hospital over a 5-year period were retrospectively included. Results: Overall, forty patients (50%) had a history of neoplasia, and this group was characterized by less atopy (p<0.004). No significant difference was observed between oncological and non-oncological patients in terms of gender, age, cardiovascular diseases, medical treatment, and number of previous exposures or reactions to ICM. Conclusion: A high proportion of oncological patients was observed in our population with HS to ICM. They did not have other known risk factors, and they were less atopic. Larger multicentric studies should explore cancer as a potential new risk factor.

In chronic obstructive pulmonary disease (COPD), exacerbations cause acute inflammatory flare-ups and increase the risk for hospitalization and mortality. Exacerbations are common in all disease stages and are often caused by bacterial infections e.g., non-typeable Heamophilus influenzae (NTHi). Accumulating evidence also associates vitamin D deficiency with the severity of COPD and exacerbation frequency. However, it is still unclear whether vitamin D deficiency when combined with cigarette smoking would worsen and prolong exacerbations caused by repeated infections with the same bacterial strain. Vitamin D sufficient (VDS) and deficient (VDD) mice were exposed to nose-only cigarette smoke (CS) for 14 weeks and oropharyngeally instilled with NTHi at week 6, 10 and 14. Three days after the last instillation, mice were assessed for lung function, tissue remodeling, inflammation and immunity. The impact of VDD and CS on inflammatory cells and immunoglobulin (Ig) production was also assessed in non-infected animals while serum Ig production against NTHi and dsDNA was measured in COPD patients before and 1 year after supplementation with Vitamin D3. VDD enhanced NTHi eradication, independently of CS and complete eradication was reflected by decreased anti-NTHi Ig's within the lung. In addition, VDD led to an increase in total lung capacity (TLC), lung compliance (Cchord), MMP12/TIMP1 ratio with a rise in serum Ig titers and anti-dsDNA Ig's. Interestingly, in non-infected animals, VDD exacerbated the CS-induced anti-NTHi Ig's, anti-dsDNA Ig's and inflammatory cells within the lung. In COPD patients, serum Ig production was not affected by vitamin D status but anti-NTHi IgG increased after vitamin D3 supplementation in patients who were Vitamin D insufficient before treatment. During repeated infections, VDD facilitated NTHi eradication and resolution of local lung inflammation through production of anti-NTHi Ig, independently of CS whilst it also promoted autoantibodies.

Cutaneous leishmaniasis (CL) is a chronic infectious skin disease caused by a group of protozoan parasites of the Leishmania genus. Parasites are transmitted to humans via the bite of sandflies. Leishmania aethiopica, one of the most neglected species, is the main causative agent of CL in Ethiopia, with infection characterized by reduced sensitivity to conventional drugs. Although the incidence of imported cases of CL is increasing in nonendemic areas, L aethiopica is rarely reported in travelers. We report a case of localized CL due to L aethiopica in a Belgian traveler. [...]

Ooglidoedeem is een veelvoorkomende reden voor een consultatie bij de dermatoloog. Omdat er zoveel mogelijke oorzaken zijn, is vaak een doorgedreven onderzoek vereist, waarin de ondervraging van de patiënt altijd een cruciale rol speelt, zoals de hierna beschreven casus illustreert. Het betreft een patiënt met een bilateraal ooglidoedeem als gevolg van het gebruik van CPAP (continuous positive airway pressure), en dit in het kader van een entiteit die soms wordt miskend door dermatologen: het floppy eyelid syndrome (of syndroom van hyperlaxe oogleden).

Les œdèmes palpébraux constituent un motif de consultation fréquent en dermatologie. La multiplicité des étiologies potentielles requiert régulièrement un bilan approfondi au sein duquel l’interrogatoire du patient demeure fondamental, comme l’illustre le cas rapporté ci-dessous. Il s’agit d’un patient ayant développé un œdème palpébral bilatéral suite à l’utilisation d’une CPAP (continuous positive airway pressure), et ce dans le cadre d’une entité méconnue des dermatologues: le floppy eyelid syndrome (ou syndrome des paupières hyperlaxes).

La prévalence de l’allergie aux fruits est fréquente. La prévalence de l’allergie sévère aux fruits exotiques est faible (entre 3–7 % des cas d’anaphylaxie d’origine alimentaire rapportés en Europe entre 2006 et 2017) [1]. Les allergènes connus des fruits exotiques sont abordés ainsi que les modifications de leur expression en fonction du contrôle de la maturation et des conditions de transport.

An 82-year-old man presented with unilateral oedema of the right lower limb overlaid with multiple sporotrichoid distributed panniculitis lesions. These symptoms appeared in a context of immunodepression and were associated with significant weight loss and a deterioration in general condition. The patient's medical history, the histological findings, PCR testing, and bacterial culture led to a diagnosis of cutaneous tuberculosis due to Mycobacterium bovis. This infection occurred as a late complication of intravesical bacillus Calmette-Guérin (BCG) instillations that the patient had received as an adjunctive immunotherapy for bladder cancer. This is an unusual clinical presentation and aetiology of cutaneous tuberculosis. Indeed, the observed sporotrichoid pattern is uncommon for tuberculous mycobacteria. Moreover, the occurrence of tuberculous skin lesions after intravesical BCG instillations is extremely rare, with only a few cases described, and, to the authors' knowledge, none with such a clinical presentation. This case report suggests that a medical history of BCG immunotherapy should always be considered when assessing any infectious-type cutaneous lesions and that skin should be regarded as a possible late localization of infectious complications of this treatment.

Entre 2002 et 2020, 172 anaphylaxies alimentaires observées chez le sénior ont été rapportées au RAV. On observe un sex-ratio H/F de 0,85 et une moyenne d’âge de 67,3 ans (60–93). Les allergènes les plus fréquents sont d’origine végétale : en premier, les légumineuses (20 cas), puis les céréales (16 cas) et les fruits à coque (15 cas), principalement la noisette. Les protéines PR-10 sont en cause dans au moins 11,7 % des anaphylaxies. À l’instar du soja, les anaphylaxies attribuées à Cor a 1 sont surtout rapportées par des allergologues exerçant en Belgique et dans le nord-est de la France. Les anaphylaxies liées aux viandes rouges et abats sont les plus fréquentes (24 cas soit 13,9 %), toujours associées à un syndrome alphaGal quand il est recherché, 16 sont attribuées aux crustacés, 8 aux mollusques et aux poissons respectivement et 6 cas à Anisakis. Cette série confirme la rareté de l’allergie au lait de vache et à l’œuf chez le sénior. Le RAV a colligé 4 anaphylaxies de grade I, 77 de grade II, 84 de grade III et 5 de grade IV dont un décès. La gravité est significativement liée à des antécédents de cardiopathie ou HTA. Quarante pour cent des sujets avaient déjà présenté une allergie dans le passé avec l’aliment suspecté et seulement 55 % disposaient d’un stylo d’adrénaline et 33 % d’un plan d’action. Cette grande série souligne l’intérêt d’un bilan allergologique détaillé chez le sujet âgé. Leur prise en charge doit non seulement comporter un protocole de soins d’urgence avec auto-injecteur d’adrénaline, mais aussi une éducation thérapeutique et diététique pour le patient et son entourage. Elle devrait être formalisée par un PAI, à l’instar de l’enfant scolarisé, compte tenu du risque de récidive, des comorbidités et perte d’autonomie pour certains.

L’angioedème (AO) qu'il soit lié à la libération d'histamine ou à la présence excessive de bradykinine représente un motif fréquent d’admission en salle d’urgence. Il s’agit aussi d’une affection potentiellement grave voire fatale. Sa prise en charge diagnostique et thérapeutique peut se révéler difficile. Cet article détaille la gestion pratique de l’AO en salle d’urgence, en particulier sa forme bradykinique, ainsi que les modalités et objectifs du bilan allergologique spécialisé fréquemment indiqué. Finalement, cet article accorde une place toute particulière à l’AO héréditaire, une maladie rare justifiant une prise en charge thérapeutique spécialisée et récemment révolutionnée par de nouvelles molécules très prometteuses.

Background: Hypersensitivity reactions (HSR) to antineoplastic agents are an increasing problem, especially when they lead to treatment discontinuation, sometimes without any equivalent therapeutic option. HSR to folinic acid (FA), used particularly for the treatment of digestive carcinoma along with oxaliplatin and 5-fuorouracil, are rare. Only seven publications report HSR to FA, mainly confrmed by the disappearance of symptoms after the withdrawal of FA from chemotherapy. Only two papers describe allergy testing. Due to the difcult diagnosis, patients usually receive several further cycles of chemotherapy with progressively more intense symptoms before the withdrawal of FA. Case presentation: Here we document two cases of HSR to FA, initially misattributed to oxaliplatin. The frst patient described successive cycles with frst back muscle pain, then chills and facial oedema and fnally difuse erythema with labial edema despite premedication. The allergy assessment highlighted high acute tryptase levels and intradermal tests positive for FA, pointing to an immunoglobulin E (IgE)-mediated mechanism. The second patient also had lower back muscle pain and chills in addition to tachycardia and desaturation during the administration of FA. Skin tests were negative and tryptase levels normal. After withdrawing FA, the symptoms did not recur, thus allowing the patient to continue chemotherapy. The mechanism of FA hypersensitivity is still unclear. The chronology of symptoms suggests an IgE-mediated mechanism that was not documented in the allergy assessment. A non-IgEmediated mast cell/basophil activation could be involved, through complement activation or through Mas-related G protein-coupled receptors X2 (MRGPRX2) particularly. Conclusions: These two cases of anaphylaxis to FA document the clinical manifestations associated with two diferent mechanisms of HSR. This paper provided the opportunity to review the limited literature on HSR to FA. Through these cases, we hope

Introduction Les patients oncologiques sont régulièrement exposés aux produits de contrastes iodés (PCI) et certaines données de la littérature suggèrent une prévalence plus élevée d’hypersensibilité aux PCI en raison de leurs traitements spécifiques. Méthodes Nous avons analysé rétrospectivement tous les patients évalués entre 01/2015 et 12/2019 pour une réaction suspecte d’hypersensibilité aux PCI (immédiate ou retardée) afin de caractériser leurs facteurs de risques, en particulier en cas de maladie néoplasique associée. Résultats Quatre-vingt patients ont été inclus, 15 d’entre eux (18,75 %) ont eu des tests cutanés positifs (9 en lecture immédiate, 6 en lecture retardée), ce taux est similaire aux études antérieures. Quarante patients (50 %) avaient un statut oncologique, dont 32 actifs et 10 étaient en cours de traitement. L’analyse multivariée portant sur 45 patients ayant présenté une réaction immédiate (IgE-médiée ou non), incluant plusieurs cofacteurs (sexe, cancer, atopie, maladies cardiovasculaires, traitement en cours et exposition antérieure) n’a pas démontré de relation significative entre le statut oncologique et l’incidence de réaction d’hypersensibilité aux PCI. La rhinite allergique était significativement plus fréquente au sein de la population non oncologique (p<0,05). Conclusion Le statut oncologique et les traitements associés en tant que facteurs de risque de réaction d’hypersensibilité aux PCI restent peu clairs. Notre étude n’a pas pu le démontrer en raison d’un nombre insuffisant de patients. Cette hypothèse mériterait d’être explorée au sein de plus larges populations. L’incidence de la rhinite allergique était significativement plus élevée au sein de la population non oncologique. Le lien entre l’atopie et le cancer fait toujours actuellement débat, toutefois le tableau prédominant des études épidémiologiques semble indiquer une plus faible incidence de cancers en cas d’atopie.

No abstract available

BACKGROUND: The diagnosis of cutaneous leishmaniasis (CL) is often difficult because of the diversity of clinical presentations, its often-misleading appearance and the very long incubation period (time between the endemic stay and the onset of skin lesions). CASE: We report the case of an otherwise healthy 67-year-old man who presented with inflammatory skin lesions on the scalp and face for the past 7 years. The lesions were first mistaken as cutaneous sarcoidosis, mycobacterial infection, and cutaneous lymphoma. Finally, the diagnosis was made by RT-PCR analysis on a punch-biopsy specimen, which was positive for Leishmania infantum. DISCUSSION AND CONCLUSION: To date, the choice of treatment for complex cutaneous leishmaniases is based on the Leishmania species. Our patient successfully responded to liposomal amphotericin B.

Pediatric LT are at particular risk of HAT, and its management still constitutes a matter of debate. Our purpose was to study predisposing factors and outcome of HAT post-LT, including the impact of surgical revisions on survival and biliary complications. Among 882 primary pediatric LT performed between 1993 and 2015, 36 HAT were encountered (4.1%, 35 fully documented). Each HAT case was retrospectively paired with a LT recipient without HAT, according to diagnosis, age at LT, type of graft, and era. Five-year patient survivals were 77.0% versus 83.9% in HAT and non-HAT paired groups, respectively (P = .321). Corresponding graft survivals were 20.0% versus 80.5% (P < .001), and retransplantation rates 77.7% versus 10.7%, respectively (P < .001). One-year biliary complication-free survivals were 16.6% versus 83.8% in the HAT and non-HAT groups, respectively (P < .001). Regarding chronology of surgical re-exploration, only HAT cases that occurred within 14 days post-LT were re-operated, fourteen of them being explored within 7 days post-LT (revascularization rate: 6/14), versus two beyond 7 days (no revascularization). When revascularization was achieved, graft and biliary complication-free survival rates at 1 year were 33.3% and 22.2%, respectively, both rates being 0.0% in case of failure. The pejorative prognosis associated with HAT in terms of graft survival is confirmed, whereas patient survival could be preserved through retransplantation. Results suggest that HAT should be re-operated if occurring within 7 days post-LT, but not beyond.

Many insect species are associated with bacterial partners that can significantly influence their evolutionary ecology. Compared to other insect groups, aphids harbor a bacterial microbiota that has the reputation of being poorly diversified, generally limited to the presence of the obligate nutritional symbiont Buchnera aphidicola and some facultative symbionts. In this study, we analyzed the bacterial diversity associated with the dogwood-grass aphid Anoecia corni, an aphid species that spends much of its life cycle in a subterranean environment. Little is known about the bacterial diversity associated with aphids displaying such a lifestyle, and one hypothesis is that close contact with the vast microbial community of the rhizosphere could promote the acquisition of a richer bacterial diversity compared to other aphid species. Using 16S rRNA amplicon Illumina sequencing on specimens collected on wheat roots in Morocco, we identified 10 bacterial operational taxonomic units (OTUs) corresponding to five bacterial genera. In addition to the obligate symbiont Buchnera, we identified the facultative symbionts Serratia symbiotica and Wolbachia in certain aphid colonies. The detection of Wolbachia is unexpected as it is considered rare in aphids. Moreover, its biological significance remains unknown in these insects. Besides, we also detected Arsenophonus and Dactylopiibacterium carminicum. These results suggest that, despite its subterranean lifestyle, A. corni shelter a bacterial diversity mainly limited to bacterial endosymbionts.

Toxocara canis and Toxocara cati are globally distributed roundworms and causative agents of human toxocariasis, via ingestion of Toxocara eggs. Control of Toxocara infections is constrained by a lack of sensitive methods for screening of animal faeces and environmental samples potentially contaminated by Toxocara eggs. In this work, a pre-analytical method for efficient extraction of DNA from Toxocara eggs in environmental samples was set up using our previously validated T. canis- and T. cati-specific quantitative real-time polymerase chain reaction (qPCR). For this purpose, the influence of different methods for egg lysis, DNA extraction and purification for removal of PCR inhibitors were assessed on environmental samples. To select the best egg disruption method, six protocols were compared on pure T. canis egg suspensions, including enzymatic lysis and thermal or mechanical disruption. Based on the selected best method, an analytical workflow was set up to compare two DNA extraction methods (FastDNA™ SPIN Kit for Soil versus DNeasy PowerMax Soil Kit) with an optional dilution and/or clean-up (Agencourt AMPure) step. This workflow was evaluated on 10-g soil and 10-g sand samples spiked with egg suspensions of T. canis (tenfold dilutions of 10 eggs in triplicate). The capacity of the different methods, used alone or in combination, to increase the ratio of positive tests was assessed. The resulting optimal workflow for processing spiked soil samples was then tested on environmental soil samples and compared with the conventional flotation-centrifugation and microscopic examination of Toxocara eggs. The most effective DNA extraction method for Toxocara eggs in soil samples consisted in the combination of mechanical lysis of eggs using beads, followed by DNA extraction with the DNeasy PowerMax Soil Kit, and completed with an additional DNA clean-up step with AMPure beads and a sample DNA dilution (1:10). This workflow exhibited a limit of detection of 4 and 46 T. c

In the case of rapid outbreaks of infectious diseases in remote locations, the lack of real-time information from the field and rapid spread of misinformation can be a major issue. To improve situational awareness and decision-making at all levels of operational deployment, there is an urgent need for accurate, reliable, and timely results from patients from the affected area. This requires a robust and fast channel of communication connecting first responders on-site, crisis managers, decision-makers, and the institutions involved in the survey of the crisis at national, regional, and international levels. This has been the rationale sustaining the development of advanced communication tools in the Biological Light Fieldable Laboratory for Emergencies (B-LiFE). The benefit of terrestrial (TETRA, LTE, 5G, and Wi-Fi-Fi) and SatCom communications is illustrated through a series of missions and exercises conducted in the previous five years. These tools were used by B-LiFE operators to provide accurate, comprehensive, timely, and relevant information and services in real time. The focus of this article is to discuss the development and benefits of the integration of multi-mission, multi-user nomadic, rapidly deployable telecommunication nodes for emergency uses (TEN) in the capacity of B-LiFE. Providing reliable communication channels through TEN enables the development and use of an ICT toolbox called MIML_LIMS (multi-institution, multi-mission, multi-laboratory LIMS), a tool which is mandatory for efficient and secure data management and data sharing by a mobile laboratory.

Editor, Acro-ischaemic lesions have been observed both in adults withsevere forms of COVID-19 and in younger patients with no ormild symptoms of COVID-19 [...]

The 3TR (Taxonomy, Treatments, Targets and Remission) consortium is the largest IMI (Innovative Medicine Initiative) project ever started in the field of immune diseases (https://3tr-imi.eu/). 3TR is unique in bringing several medical specialties, encompassing respiratory medicine, rheumatology, neurology and gastroenterology, together, to study disease mechanisms across seven disease entities: asthma, COPD, systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, ulcerative colitis and Crohn's disease. [...]

Objective: Patients with severe asthma require high-dose inhaled corticosteroids, with or without add-on treatments, to maintain asthma control. Because symptom control remains unsatisfactory in some patients despite these therapies, maintenance therapy with oral corticosteroids (OCS) remains considered a treatment option by physicians. Besides physician-diagnosed exacerbations, many patients intermittently self-medicate with OCS during episodes of worsening symptoms or as a prevention of such episodes. However, long-term OCS use is associated with several comorbidities that may decrease health-related quality of life, worsen prognosis, and should ideally require monitoring and management. In this review, we discuss the adverse effects of OCS use, the OCS-sparing effect of biologics in severe asthma, and the need for optimal referral pathways to ensure the best outcomes for those at-risk asthma patients. Data sources: PubMed. Study selection: Studies with results on the OCS-sparing effect of biologics in adult severe asthma were selected. Results: Chronic and intermittent OCS use in asthma is associated with considerable adverse effects in asthma. Omalizumab, mepolizumab, benralizumab, and dupilumab reduce the need for OCS in severe asthma, while also reducing the exacerbation rate and improving several patient-related outcomes. Conclusion: Targeted biologic therapies have revolutionized the treatment of uncontrolled severe asthma by reducing or even eliminating the need for OCS and improving other major outcomes. Novel agents are now rapidly increasing the therapeutic armamentarium, but additional efforts are needed to optimize referral pathways in order to ensure sustainable access to these therapies.

No abstract available

In March and April 2020, at the peak of the COVID-19 pandemic, several countries imposed lockdown measures. Concurrently, a significant number of chilblains were observed in otherwise healthy adolescents and young adults. The physiopathology of these chilblains has not been completely elucidated and their direct link to COVID-19 remains unconfirmed and debated. [...]

The coronavirus pandemic, which appeared in Wuhan, China, in December 2019, rapidly spread all over the world in only a few weeks. Faster testing techniques requiring less resources are key in managing the pandemic, either to enable larger scale testing or even just provide developing countries with limited resources, particularly in Africa, means to perform tests to manage the crisis. Here, we report an unprecedented, rapid, reagent-free and easy-to-use screening spectroscopic method for the detection of SARS-CoV-2 on RNA extracts. This method, validated on clinical samples collected from 280 patients with quantitative predictive scores on both positive and negative samples, is based on a multivariate analysis of FTIR spectra of RNA extracts. This technique, in agreement with RT-PCR, achieves 97.8% accuracy, 97% sensitivity and 98.3% specificity while reducing the testing time post RNA extraction from hours to minutes. Furthermore, this technique can be used in several laboratories with limited resources.

Background Skin exposure to chemicals may induce an inflammatory disease known as contact dermatitis (CD). Distinguishing the allergic and irritant forms of CD often proves challenging in the clinic. Methods To characterize the molecular signatures of chemical-induced skin inflammation, we conducted a comprehensive transcriptomic analysis on the skin lesions of 47 patients with positive patch tests to reference contact allergens and nonallergenic irritants. Results A clear segregation was observed between allergen- and irritant-induced gene profiles. Distinct modules pertaining to the epidermal compartment, metabolism, and proliferation were induced by both contact allergens and irritants; whereas only contact allergens prompted strong activation of adaptive immunity, notably of cytotoxic T-cell responses. Our results also confirmed that: (a) unique pathways characterize allergen- and irritant-induced dermatitis; (b) the intensity of the clinical reaction correlates with the magnitude of immune activation. Finally, using a machine-learning approach, we identified and validated several minimal combinations of biomarkers to distinguish contact allergy from irritation. Conclusion These results highlight the value of molecular profiling of chemical-induced skin inflammation for improving the diagnosis of allergic versus irritant contact dermatitis.

Background. The literature describes several risk factors for hypersensitivity (HS) reactions to iodinated contrast media (ICM). Objective. To analyze the characteristics of patients experiencing HS reactions to ICM with a focus on oncological status. Methods. All patients (n = 80) with suspected HS to ICM who underwent an allergy evaluation in a Belgian University Hospital over a 5-year period were retrospectively included. Results. Overall, forty patients (50%) had a history of neoplasia, and this group was characterized by less atopy (p < 0.004). No significant difference was observed between oncological and non-oncological patients in terms of gender, age, cardiovascular diseases, medical treatment, and number of previous exposures or reactions to ICM. Conclusions. A high proportion of oncological patients was observed in our population with HS to ICM. They did not have other known risk factors, and they were less atopic. Larger multicentric studies should explore cancer as a potential new risk factor.

Background: In our allergologial unit, it seemed that among patients evaluated for a suspicion of hypersensitivity (HS) to iodinated con-trast media (ICM), most of them were oncologic patients (just diag-nosed or with finished/ongoing treatment). Repeated exposures to ICM were previously described as a risk fac-tor of HS to ICM and they are frequent in the oncologic population Moreover, antineoplasic treatments as risk factors of HS reactions to ICM have been the topic of some studies, without clear conclusions at this time.

Genetic alterations in genes lead to peroxisome biogenesis disorder. In humans, they are associated with Zellweger spectrum disorders (ZSD). No validated treatment has been shown to modify the dismal natural history of ZSD. Liver transplantation (LT) improved clinical and biochemical outcomes in mild ZSD patients. Hepatocyte transplantation (HT), developed to overcome LT limitations, was performed in a mild ZSD 4-year-old child with encouraging short-term results. Here, we evaluated low dose (12.5 million hepatocytes/kg) and high dose (50 million hepatocytes/kg) syngeneic male HT via intrasplenic infusion in the -G844D NMRI mouse model which recapitulates a mild ZSD phenotype. HT was feasible and safe in growth retarded ZSD mice. Clinical (weight and food intake) and biochemical parameters (very long-chain fatty acids, abnormal bile acids, etc.) were in accordance with ZSD phenotype but they were not robustly modified by HT. As expected, one third of the infused cells were detected in the liver 24 h post-HT. No liver nor spleen microchimerism was detected after 7, 14 and 30 days. Future optimizations are required to improve hepatocyte engraftment in -G844D NMRI mouse liver. The mouse model exhibited the robustness required for ZSD liver-targeted therapies evaluation.

Objective: Olfactory disorders may be associated with different etiologies, including upper respiratory infections, sinonasal conditions, head injuries, exposure to toxins, and congenital anosmia. This study aimed to evaluate the prevalence of different etiologies for olfactory dysfunction as observed in a sub-Saharan African population. Methods: This descriptive cross-sectional study was conducted in a series of 116 consecutive patients with an olfactory disorder who lived in the city of Bukavu in the South Kivu province of the Democratic Republic of the Congo. The study was conducted from June 1, 2016 to May 30, 2017. We used the Sniffin’ Sticks test, adapting the identification (I) test to our population but retaining the standard threshold (T) and discrimination (D) tests. The patients were classed as anosmic if their composite T + D + I score was <16, hyposmic if it was 16–30, and normosmic if it was >30. Informed consent was obtained in accordance with the Declaration of Helsinki II. We calculated proportions for each olfactory disorder. Results: Median age (minimum–maximum) in our 116 patients was 42.5 (18–83) years. Women made up 60% of our sample. It was observed that 70.7% of patients had anosmia and 29.3% hyposmia. In descending order, the main causes were upper respiratory infections (49.1%), congenital causes (34.5%), nasal polyps (6%), nose and/or sinus surgery (3.4%), head injuries (2.6%), metabolic causes (2.6%), and occupational exposure to toxins (1.7%). Hyposmia predominated when the cause was upper respiratory infection, whereas anosmia did when the cause was congenital and noninfectious. Conclusion: In our study population, upper respiratory infections were the main cause of dysosmia. The anosmic cases we observed tended to be congenital in nature, suggesting that there existed other etiological factors that require further investigation.

Auditory neuropathy spectrum disorder (ANSD) refers to a range of hearing impairments characterized by deteriorated speech perception, despite relatively preserved pure-tone detection thresholds. Affected individuals usually present with abnormal auditory brainstem responses (ABRs), but normal otoacoustic emissions (OAEs). These electrophysiological characteristics have led to the hypothesis that ANSD may be caused by various dysfunctions at the cochlear inner hair cell (IHC) and spiral ganglion neuron (SGN) levels, while the activity of outer hair cells (OHCs) is preserved, resulting in discrepancies between pure-tone and speech comprehension thresholds. The exact prevalence of ANSD remains unknown; clinical findings show a large variability among subjects with hearing impairment ranging from mild to profound hearing loss. A wide range of prenatal and postnatal etiologies have been proposed. The study of genetics and of the implicated sites of lesion correlated with clinical findings have also led to a better understanding of the molecular mechanisms underlying the various forms of ANSD, and may guide clinicians in better screening, assessment and treatment of ANSD patients. Besides OAEs and ABRs, audiological assessment includes stapedial reflex measurements, supraliminal psychoacoustic tests, electrocochleography (ECochG), auditory steady-state responses (ASSRs) and cortical auditory evoked potentials (CAEPs). Hearing aids are indicated in the treatment of ANSD with mild to moderate hearing loss, whereas cochlear implantation is the first choice of treatment in case of profound hearing loss, especially in case of IHC presynaptic disorders, or in case of poor auditory outcomes with conventional hearing aids.

RATIONALE: Accumulation of B cells and lymphoid follicles (LFs) has been described in chronic obstructive pulmonary disease (COPD) airways, but the functional status of lung B cells remains poorly known. OBJECTIVES: To characterize LFs for expression of IgA, the main mucosal antibody. METHODS: The presence of B cells and LFs, including intrafollicular IgA expression, were determined in the lung from patients with COPD (n = 37) versus control subjects (n = 34) by immunohistochemistry. We also evaluated follicular IgA responses in the lungs from mice infected with Pseudomonas aeruginosa (PAO1) (n = 10 per group) and in smoking mice. MEASUREMENTS AND MAIN RESULTS: Whereas in smokers B-cell numbers slightly increased, robust increases in B-cell and LF numbers (mainly in distal airways) were only observed in severe COPD. Most follicular B cells were IgM+ (70-80%), but IgA+ (and not IgG+) B-cell numbers were increased in LFs from severe COPD compared with control subjects (twofold, 44.7% vs. 25.2%), and this was significant in distal but not proximal airways. Follicular IgA response was also observed in PAO1-infected mouse lungs, but not after smoke exposure. Moreover, follicular IgA expression associated with expression of IL-21, which was very potent to activate immunoglobulin production in vitro. CONCLUSIONS: This study shows that IgA production occurs in peribronchiolar LFs from severe COPD, where IL-21-producing T cells are present, and presumably represents a feature of exacerbated mucosal adaptive immune responses against microbial and/or self-antigens.

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators are small molecules aimed at improving CFTR function by specifically targeting the different classes of CFTR mutations. Recent Phase II studies of triple therapy, including new generation correctors, have demonstrated spectacular improvements in forced expiratory volume in 1s (FEV1), likely to translate into improved quality of life and increased life expectancy. Within the next 5 years, a highly effective CFTR modulator therapy will probably be approved for most cystic fibrosis patients, including those carrying at least one copy of the F508del mutation (88% of Belgian patients). Patients with well-preserved lungs will benefit most from these treatments.

INTRODUCTION : C’est dans les voies aériennes périphériques qu’apparaissent les premières anomalies pulmonaires dans la mucoviscidose. Très précoce, cette atteinte est d’abord infraclinique et évolue insidieusement puisque ces petites voies aériennes (PVA) sont relativement ignorées par les épreuves fonctionnelles respiratoires conventionnelles. ÉTAT DES CONNAISSANCES : La méthode de rinçage d’un gaz inerte, qui donne accès à l’indice de clairance pulmonaire (ICP), est non invasive et plus abordable que les autres techniques d’investigation des PVA. L’ICP est reproductible et nettement plus sensible à une atteinte des PVA que les indices dérivés de la spirométrie. Le test requiert de l’opérateur un investissement important. PERSPECTIVES : La récente commercialisation d’appareils mesurant l’ICP laisse entrevoir son application au domaine clinique. Cependant, les valeurs d’ICP sont tributaires de l’équipement utilisé, ce qui soulève de nombreuses questions théoriques. Les algorithmes spécifiques devraient être améliorés et plus transparents. La standardisation du test reste perfectible. D’autres indices dérivés du test mériteraient d’être davantage étudiés. CONCLUSIONS : L’ICP a sa place en recherche pour détecter précocement les anomalies pulmonaires fonctionnelles dans la mucoviscidose et évaluer l’efficacité de nouveaux traitements, notamment chez les patients avec une fonction pulmonaire préservée. Son intérêt en pratique clinique apparaît probable mais reste à préciser., [Lung clearance index in cystic fibrosis] INTRODUCTION : Small airways’ involvement in cystic fibrosis (CF) pulmonary disease is a very early event, which can progress sub-clinically and insidiously since it is poorly reflected by commonly used lung function tests. STATE OF ART : Sensitive and discriminative tools are available to investigate small airways function. However their complexity and/or invasiveness has confined their use to research purposes and to some specialized research teams. By contrast, the multiple breath washout (MBW) test is more affordable and non-invasive. Lung clearance index (LCI), which is the most used derived parameter, is reproducible and much more sensitive than spirometry in detecting small airways disease. However, MBW is operator dependent. PERSPECTIVES : The recent commercialization of devices assessing LCI launches MBW as a potential tool in routine clinical care, although its use currently remains mostly dedicated to research purposes. However, important differences in LCI between various equipment settings raise a number of theoretical questions. Specific algorithms should be refined and more transparent. Standardization of MBW is still an ongoing process. Whether other MBW derived indices can prove superior over LCI deserves further study. CONCLUSIONS : In CF, LCI is now a well-established outcome in research settings to detect early lung function abnormalities and new treatment effects, especially in patients with mild lung disease. In these patients, LCI seems an attractive tool for clinicians too. Yet, further investigation is needed to define clinically significant changes in LCI and to which extent this index can be useful in guiding clinical decisions remains to be studied.

Les allergies de contact peropératoires ne peuvent en principe et par définition qu’être des allergies de type I. L’urticaire de contact aux protéines du latex en représente l’exemple majeur bien que leur fréquence ait nettement diminué depuis quelques années. Les eczémas allergiques de contact « peropératoires » (allergie de type IV) ne surviennent jamais pendant les opérations chirurgicales. S’ils sont déclenchés pendant l’intervention, ils ne s’observent qu’au cours des jours qui suivent. Les dermatites de contact allergiques aux accélérateurs de vulcanisation des gants de caoutchouc (naturel ou synthétique) restent d’une actualité brûlante et représentent un problème majeur tant pour le personnel travaillant en salle d’opération que pour le patient « subissant » une intervention chirurgicale !, [Intraoperative contact allergies] In principle and by definition, intraoperative contact allergies can only be type I allergies. Contact urticaria with latex proteins is the best example, even though their frequency has significantly decreased in the past years. “Intraoperative” allergic contact dermatitis (type IV allergy) never occurs during surgery. If they are triggered during the procedure, they only are observed during the following days. Allergic contact dermatitis to vulcanization accelerators of rubber gloves (natural or synthetic) remains hot news and represents a huge problem for both the staff working in the operating room and the patient “undergoing” surgery!

It is currently unknown how cigarette smoke-induced airway remodelling affects highly expressed respiratory epithelial defence proteins and thereby mucosal host defence.Localisation of a selected set of highly expressed respiratory epithelial host defence proteins was assessed in well-differentiated primary bronchial epithelial cell (PBEC) cultures. Next, PBEC were cultured at the air-liquid interface, and during differentiation for 2-3 weeks exposed daily to whole cigarette smoke. Gene expression, protein levels and epithelial cell markers were subsequently assessed. In addition, functional activities and persistence of the cigarette smoke-induced effects upon cessation were determined.Expression of the polymeric immunoglobulin receptor, secretory leukocyte protease inhibitor and long and short PLUNC (palate, lung and nasal epithelium clone protein) was restricted to luminal cells and exposure of differentiating PBECs to cigarette smoke resulted in a selective reduction of the expression of these luminal cell-restricted respiratory host defence proteins compared to controls. This reduced expression was a consequence of cigarette smoke-impaired end-stage differentiation of epithelial cells, and accompanied by a significant decreased transepithelial transport of IgA and bacterial killing.These findings shed new light on the importance of airway epithelial cell differentiation in respiratory host defence and could provide an additional explanation for the increased susceptibility of smokers and patients with chronic obstructive pulmonary disease to respiratory infections

BUT DE L'ETUDE: Les accidents d’hypersensibilité allergique per-anesthésiques bien que rares constituent une complication anesthésique potentiellement lourde de conséquences. En Belgique, il n’y a actuellement aucune étude épidémiologique publiée. Ce travail vise à relater l’expérience d’un hôpital universitaire belge où sont investigués les patients après un accident suspect et analyser les particularités locales. METHODES : Les dossiers de 31 patients ayant consulté le même allergologue au sein des Cliniques Universitaires Saint-Luc pour bilan de suspicion d’hypersensibilité per-anesthésique entre 2012 et 2015 ont été analysés de manière rétrospective. Les données ont été récoltées à partir des documents de consultations (anesthésie pré-interventionnelle, allergologie) et de rapports d’anesthésie ainsi que des protocoles d’intervention médico-chirurgicale. RESULTATS : Vingt et un patients (67.7 %) ont présenté une hypersensibilité allergique per-anesthésique à une substance utilisée dans le cadre de l’anesthésie. Nonante cinq pour cents de ces réactions sont de type IgE-médié et sont généralement sévères. Les substances causales le plus souvent identifiées sont le Rocuronium, la Céfazoline, le latex et la Chlorhexidine. Des sensibilisations croisées ont été documentées pour entre curares et entre céphalosporines. Ce travail met également en évidence des dysfonctionnements qui compliquent la démarche diagnostique. CONCLUSION : Les résultats de ce travail sont comparables aux données de la littérature. Le diagnostic d’hypersensibilité allergique per-anesthésique reste difficile à poser pour de multiples raisons d’où la nécessité de documenter au mieux les différents éléments indicateurs et d’assurer une bonne communication avec l’allergologue qui devra réaliser le bilan étiologique dans un délai optimal., [Peri-anaesthetic hypersensitivity: Experience of a university hospital in Belgium] BACKGROUND : Allergic peri-anaesthetic hypersensitivity reactions are rare but can have serious consequences. In Belgium, there are currently no published epidemiological papers on this subject. The aim of this paper is to describe the experience of a Belgian university hospital where patients were examined after suspected allergic peri-anaesthetic reaction. METHODS : We retrospectively analysed the medical files of 31 patients consulting the same allergist at the cliniques universitaires Saint-Luc in Brussels between 2012 and 2015 in a context of suspected peri-anaesthetic allergic reaction. Data were collected from the pre-anaesthesia and allergology consultation files as well as the anaesthesia reports and medico-surgical reports. RESULTS : Twenty-one patients (67.7%) developed an allergic peri-anesthetic hypersensitivity reaction to a substance used during anaesthesia. Most reactions (95%) were IgE-mediated and the majority were severe. The substances most frequently incriminated were rocuronium, cefazolin, latex and chlorhexidine. Cross-sensitivities were documented for neuromuscular blocking agents and cephalosporins. This work highlights certain dysfunctions that constitute a source of error in diagnosis. CONCLUSION : The results are similar to those of other studies. The diagnosis of peri-anaesthetic allergic hypersensitivity is difficult to establish for several reasons, and it is thus important to make as accurate a record as possible of the various indicators and ensure good communication with the allergy specialist, who must prepare an etymological report as early as possible.

1 INTRODUCTION : The Rhinology Future Debates is a unique clinician‐orientated initiative organised by the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA). EUFOREA (www.euforea.eu) is an international non‐profit organisation aiming at reducing the prevalence and burden of chronic respiratory diseases. EUFOREA brings together specialists from the entire healthcare system to create opportunities for innovative thinking and development of new techniques, devices, protocols and concepts for a patient‐centred approach in prevention and optimal care.1 Advocacy for integrated care pathways and implementation of precision medicine in respiratory diseases are key priorities of the EUFOREA team.2, 3 The Rhinology Future Debates have been organised for the first time in 2016 and aim at filling the gap between industry‐investor meetings and clinicians working with patients affected by upper respiratory diseases. The debates deal with topics of innovation in diagnostic and therapeutic approaches, including novel devices, molecules and e‐health tools and other innovative solutions. The second Rhinology Future Debate took place in Brussels in December 2017 and brought together key experts in the field of respiratory diseases, industrial partners and patients for a discussion forum in the respiratory field. Debate topics in 2017 included (a) Real World Evidence data in AIT—What does it bring to us?, (b) Positioning Dymista in Allergic Rhinitis treatment (a separate report is available for this debate), (c) Nasal turbinate as therapeutic target in patients with turbinate‐induced nasal symptoms, and (d) Lessons from biologicals in asthma for ENT physicians. The debates were fully recorded and are available online (www.euforea.eu; www.rhinology-future.com) (Figure 1). This report summarises the key messages from each debate and further consolidates the discussion by providing additional evidences of the current state of the art in the field through l

PERIOPERATIVE ANAPHYLAXIS: DON’T FORGET THE MASKED CULPRIT A. JACQUERIE MD ; F. PIRSON, MDᵇ Chest Unit, Cliniques Universitaires Saint-Luc 1200 Bruxelles ᵇ Chest Unit, Centre de l’allergie Saint Luc Cliniques Universitaires Saint-Luc 1200 Bruxelles. Abstract Chlorhexidine is an effective antiseptic agent, widely used in surgical, clinical and paramedical practice. It is a potentially allergenic substance, which can be associated with severe allergic reaction, especially in perioperative context [1]. Although rare, the prevalence of these hypersentivity reactions remains unknown. We report a case of grade 3 anaphylaxis, caused by the exposure to chlorhexidine during a cardiothoracic surgery, in a 69-year-old man with no history of allergy. At the induction of anesthesia, the patient presented urticaria, rash and severe hypotension. A treatment by intravenous adrenaline and fluid resuscitation has allowed a clinical improvement and the procedure was able to continue. We performed an allergological investigation after 6 weeks. After examination of the anesthetic chart, we tested the different agents administered, and chlorhexidine systematically, with skin prick test, intradermal tests and serum-specific IgE assays (ImmunoCAP, Thermo Scientific). The skin tests [2] and the spIgE were positive for chlorhexidine, and negative for the other substances. In this case, the sources of exposure to chlorhexidine are the gel which was used during the urinary catheterization procedure and skin disinfection for the insertion of central venous catheter. Despite multiple publications on anaphylactic reactions during procedures under general anaesthesia, the role of chlorhexidine is often minimized and underdiagnosed with a risk of re-exposure. It should be recommended that all patients with perioperative allergic reactions will be tested with chlorhexidine due to widespread and often hidden exposure. In the current recommendations, the diagnosis of allergy requires 2 positive diagno

La glycogénose de type IX est une maladie métabolique héréditaire, caractérisée par l’accumulation de glycogène dans le foie suite à la déficience en phosphorylase kinase. Nous rapportons le cas d’un enfant présentant une hépatomégalie avec des transaminases et un lactate postprandial élevés, malgré une activité normale de la phosphorylase kinase érythrocytaire. Nous avons donc exclu, dans un premier temps, le diagnostic de glycogénose de type IX. Cependant, l’étude génétique nous a permis de mettre en évidence une mutation délétère déjà rapportée dans la littérature dans le gène PHKA2, confirmant finalement le diagnostic de glycogénose de type IX liée à l’X. Cette situation souligne le piège de l’activité enzymatique phosphorylase kinase érythrocytaire normale dans le cas des variants appelés XLG2