[Connective tissue diseases and pregnancy]. / Connectivites et grossesse.

Connective tissue diseases are rare usually affecting women of reproductive age. Patients should be informed about the potential obstetrical risks associated with their disease as well as potential exacerbations during pregnancy, while simultaneously being reassured with the prospect of a positive pregnancy outcome. In recent years, significant progress has been made in medical treatments, giving women the opportunity to consider pregnancy. Preconception counseling is critical to pregnancy planning. An effective contraceptive measure should be recommended based on disease activity and teratogenic medications should be modified. Pregnancy monitoring are managed based on specific clinical and serological markers (such as the presence of anti-SSA/SSB or anti-phospholipid antibodies). A multidisciplinary approach is essential for a safe pregnancy.

Les connectivites touchent souvent des femmes en âge de procréer. Les patientes doivent être informées des risques obstétricaux ou d'aggravation potentiels de leur maladie, mais également être rassurées quant à leur chance de succès de grossesse. En effet, grâce aux progrès de la médecine, il est possible de mener à bien une grossesse chez ces patientes en prenant certaines précautions. Une contraception efficace doit être mise en place en cas de maladie active, de prise de médicaments tératogènes ou fœto-toxiques. Une adaptation des traitements est donc souvent nécessaire avant la grossesse. Le suivi durant celle-ci, l'accouchement et le postpartum est conditionné par le type de maladie, son activité, ainsi que les profils sérologiques à risques (anti-SSA/SSB, anticorps antiphospholipides). Une approche multidisciplinaire est donc essentielle.

[Allergology: what's new in 2022]. / Allergologie : ce qui a changé en 2022.

The study of reactions to SARS-CoV-2 vaccines has marked a large part of the literature in the last two years, using the basophil activation test (BAT) as a potential diagnostic tool for reactions to Covid-19 vaccines. In allergic rhinoconjunctivitis, lirentelimab (a humanised monoclonal antibody against lectin 8), reduces patients' symptoms and atopic comorbidities. In severe asthma, tezepelumab (human monoclonal antibody) reduces the annual asthma exacerbation rate over 52 weeks. In terms of diet, the new EAACI guidelines recommend avoiding cow's milk supplementation in infants during the first three days of life to reduce the risk of cow's milk allergy.

L'étude des réactions aux vaccins contre le SARS-CoV-2 a marqué une grande partie des publications de ces deux dernières années, en utilisant le test d'activation de basophiles (BAT) comme outil de diagnostic potentiel pour les réactions aux vaccins contre le Covid-19. Sur le plan de la rhinoconjonctivite allergique, le lirentélimab (anticorps monoclonal humanisé contre la lectine 8) diminue les symptômes des patients et ses comorbidités atopiques. Sur le plan de l'asthme sévère, le tézépélumab (anticorps monoclonal humain) en diminue le taux d'exacerbations annuelles sur 52 semaines. Sur le plan alimentaire, les nouvelles directives EAACI (Académie européenne d'allergie et d'immunologie clinique) recommandent d'éviter la supplémentation en lait de vache chez les nourrissons au cours des 3 premiers jours de vie pour en diminuer le risque d'allergie.

[Insulin allergy: how to manage it?] / Allergie à l'insuline : comment faire ?

Insulin allergy is a rare entity, complex to manage. Several types of hypersensitivity reaction are described, depending on the allergens (insulin itself vs additives). Type I, so-called immediate, IgE-mediated reactions are the most common. Their management requires a careful history and examination, as well as an allergological consult. If an IgE-mediated allergy is confirmed, insulin avoidance is recommended whenever possible. If insulin treatment is mandatory, another type of insulin may be offered. In case of failure, desensitization should be discussed, either via a dedicated protocol, or via insulin pump. In this article, we summarize the available data from the literature.

L'allergie à l'insuline est une entité rare, complexe à prendre en charge. Plusieurs types de réactions d'hypersensibilité sont décrits, selon les agents allergènes (insuline même vs additifs). Les réactions de type I, dites immédiates, IgE (immunoglobulines E) médiées sont les plus fréquentes. Leur prise en charge nécessite une anamnèse et un examen minutieux, ainsi qu'un avis allergologique. En cas de confirmation d'allergie IgE médiée, une éviction des insulines est dans la mesure du possible recommandée. Si la poursuite des traitements insuliniques est inévitable, un autre type d'insuline peut être proposé. En cas d'échec, une induction de tolérance devrait être discutée, soit via un protocole dédié, soit via la mise sous pompe à insuline. Nous résumons dans cet article les données de la littérature à disposition.

[Consequences of antinuclear antibodies testing in clinical practice]. / Impact du dosage des anticorps antinucléaires dans la pratique clinique quotidienne.

Connectivitis or collagenosis are autoimmune multi-systemic diseases. Systemic lupus erythematous (SLE) and Sjogren's syndrome are the most common type after the rheumatoid arthritis. Antinuclear antibodies (ANA), previously called antinuclear factors, are frequently present in connectivitis. Due to their high sensitivity, they may constitute a good screening test. To avoid useless and expensive investigations following a false positive test, a high clinical suspicion is required before any further biological testing. In case of ANA positive testing and low clinical evidence, the presence of anti-DSF70 antibody enables to exclude the diagnostics with a good negative predictive value.

Les connectivites, anciennement appelées collagénoses, sont des pathologies auto-immunes avec des atteintes multisystémiques. La polyarthrite rhumatoïde en est la forme la plus fréquente, suivie par le lupus érythémateux systémique et le syndrome de Sjögren. Du fait de leur haute sensibilité dans ces maladies, les anticorps antinucléaires (AAN), autrefois appelés facteurs antinucléaires, semblent constituer un bon test de dépistage. Toutefois, en raison de leur mauvaise spécificité et afin de limiter des investigations inutiles et coûteuses dans le cas d'un test faussement positif, il faut une suspicion clinique élevée avant d'y recourir. Dans les cas d'un AAN positif avec une probabilité clinique faible, un nouveau test nous permet d'exclure un diagnostic de connectivite avec une bonne valeur prédictive négative : le dosage positif de l'anti-DFS70 (Dense Fine Speckled 70 kD).

[Red meat allergy]. / Allergie à la viande rouge.

The goal of this article is to provide an informative review on allergy to mammalian meat. The main allergen contained in «â€…red meat ¼ is the alpha-gal (galactose-alpha-1,3-galactose) that is found in all non-primate mammalian tissues. IgE-mediated allergy to alpha-gal appears typically delayed from the consumption of meat, often three to six hours after ingestion of meat. Common allergic reactions include isolated gastrointestinal symptoms but can potentially be life-threatening with severe anaphylaxis. Diagnosis relies on a thorough clinical history, skin-prick testing and the search for specific IgE. The management of meat allergy consists in the avoidance of all mammalian meat (including gelatins) and other pharmaceutical products that can contain alpha-gal, especially cetuximab.

L'objectif de cet article est d'informer le praticien sur l'allergie à la viande de mammifère. L'allergène principal de la viande «â€…rouge ¼ est l'alpha-gal (galactose-alpha-1,3-galactose) présent dans les viandes et tissus des mammifères non primates. Il peut ­entraîner des anaphylaxies immédiates IgE-médiées, dont les symptômes sont typiquement à distance de la prise alimentaire, le plus souvent 3 à 6 heures après l'ingestion. Les réactions ­comprennent souvent, voire uniquement, des manifestations gastro-intestinales, mais peuvent aller jusqu'à des anaphylaxies de stade IV. Une bonne anamnèse, des tests cutanés et la recherche d'IgE spécifiques sanguins permettent de poser le diagnostic. L'attitude consiste à éviter strictement toute consommation de viande de mammifères (y compris les gélatines) ainsi que ­l'exposition à des produits qui peuvent contenir de l'alpha-gal, notamment le cétuximab.

[How to manage giant cell arteritis]. / Allergologie-immunologie - Prise en charge de l'artérite gigantocellulaire en 2019.

Giant cell arteritis (GCA) is the most common vasculitis in adults over 50 years, which requires an urgent treatment with corticosteroids to reduce ischemic complications. Because of their side-effects, a valid diagnosis is necessary. Histological confirmation remains the gold-standard but non-invasive imaging along specific clinical criteria can nowadays diagnose GCA, particularly temporal artery ultrasound. Alternatives to corticosteroids are being studied and recently, the addition of tocilizumab to corticosteroids has been validated by international institutions and is approved by Swissmedic. Similarly to tocilizumab, methotrexate has been shown to decrease the total dose of corticosteroids and the number of relapses. We will also discuss newer potential therapies (abatacept and ustekinumab).

L'artérite à cellules géantes est une vasculite des gros vaisseaux fréquentes après 50 ans, nécessitant un traitement par corticostéroïdes dès le diagnostic pour diminuer les complications ischémiques. En raison des effets secondaires du traitement, une certitude diagnostique est importante. Bien que la confirmation histologique reste le gold standard, l'imagerie permet désormais de poser un diagnostic non invasif en présence de critères bien définis. Des alternatives aux stéroïdes sont étudiées et récemment, l'adjonction de tocilizumab a été validée par Swissmedic, entre autres dans le but de diminuer la dose totale de stéroïdes et le nombre de rechutes. Le méthotrexate, alternative au tocilizumab, existe et est toujours d'actualité. Nous discuterons également de l'abatacept et de l'ustékinumab, molécules prometteuses en cours d'évaluation.

[Place of immunotherapy in allergic asthma]. / Place de l'immunothérapiedans l'asthme allergique.

Desensitization for pneumallergens is used in daily practice for the treatment of allergic rhinitis and allergic asthma. However, specific immunotherapy has long been debated in the medical literature as a treatment for allergic asthma until the latest international recommendations for the management of asthma (GINA) reveal specific immunotherapy as a treatment in sensitized patients, poorly controlled by inhaled corticosteroids (FEV 1 > 70%). In this article you will find a current overview of the medical literature on the usefulness of specific desensitization to reduce asthma symptoms and symptomatic treatments, prevent the onset of asthma in patients with allergic rhinitis as well as prevent new sensitizations.

La désensibilisation pour les pneumallergènes est utilisée en pratique quotidienne pour le traitement de la rhinite et de l'asthme allergiques. Cependant, l'efficacité de l'immunothérapie spécifique sur l'asthme allergique a longtemps été débattue dans la littérature médicale jusqu'à ce que les dernières recommandations internationales pour la prise en charge de l'asthme (GINA) fassent apparaître l'immunothérapie spécifique comme traitement des patients sensibilisés aux acariens et mal contrôlés par les corticostéroïdes inhalés (VEMS > 70%). Cet article résume l'utilité de la désensibilisation spécifique sur la diminution des symptômes de l'asthme et l'utilisation de traitements symptomatiques ainsi que sur la prévention de nouvelles sensibilisations et de l'apparition de l'asthme chez les patients atteints de rhinite allergique.

Elevated serum levels of free interleukin-18 in adult-onset Still's disease.

OBJECTIVE: IL-18 is a pro-inflammatory cytokine of the IL-1 family that is naturally inhibited by IL-18 binding protein (IL-18BP). High levels of IL-18 have been described in the serum of adult-onset Still's disease (AOSD) patients, but only total IL-18 levels (including inactive IL-18 bound to IL-18BP) have been measured. With a specific immunoassay, we aimed to measure free IL-18 serum levels in AOSD patients and other rheumatic diseases. METHODS: An ELISA was developed to measure free IL-18. Its sensitivity and specificity were tested by spiking recombinant IL-18 or IL-18BP in serum and PBS supplemented with 5% BSA. The binding affinity of IL-18 to IL-18BP was calculated by titration experiments using the ELISA and by Biacore analysis. Sera of 37 AOSD patients and 138 controls (40 healthy controls, 30 RA, 29 SLE, 21 AS and 18 PsA) were assayed for free IL-18, IL-18BP, total IL-18 and other cytokines. Correlations were performed between free IL-18 and markers of disease activity in AOSD patients. RESULTS: Free IL-18 serum levels were significantly higher in AOSD patients (median 8.89 pg/ml) than in healthy and disease controls (1.37 pg/ml; P < 0.01). Free IL-18 serum levels correlated with AOSD activity. The affinity of IL-18 to IL-18BP was found to be much higher than previously described, with a dissociation constant ranging from 30 to 50 pM. CONCLUSION: Free IL-18 levels are specifically elevated in AOSD compared with other inflammatory diseases, suggesting that IL-18 represents a potential target for the treatment of AOSD.

Pancreaticoduodenal Artery Pseudoaneurysm Associated with Pancreatic Fibroinflammatory Mass and Duodenal Obstruction.

BACKGROUND When people in their 60s experiences abdominal pain, vomiting, and unexplained weight loss without a history of abdominal surgery, the usual diagnosis is obstruction caused by a neoplastic mass. Nevertheless, in exceptionally rare cases, these symptoms arise from complications linked to a visceral artery aneurysm. CASE REPORT We present a case of a 60-year-old man with immunodeficiency and Sneddon-Wilkinson disease (a rare subcorneal pustular dermatosis), who developed a pancreaticoduodenal aneurysm of uncertain origin, associated with pancreatic mass, retroperitoneal hematoma, and duodenal obstruction. The treatment approach included transcatheter arterial coil embolization with supportive measures such as parenteral nutrition, a nasogastric tube, octreotide administration, and antiemetics. Despite these interventions, persistence gastrointestinal symptoms prompted an endoscopic ultrasound fine-needle aspiration to rule out malignancy. The biopsy confirmed localized fibro-inflammation. Although he was initially considered for a gastro-jejunal bypass, conservative management effectively improved the pancreatic lesion and duodenal obstruction, leading to discontinuation of parenteral nutrition. The patient was able to resume a regular diet 4 weeks after embolization. CONCLUSIONS Pancreaticoduodenal artery aneurysm is a rare visceral aneurysm with multiple etiologies and potentially fatal consequences. We report an unusual case of a pancreaticoduodenal artery aneurysm associated with pancreatic mass and duodenal obstruction. This diagnosis warrants consideration when an immunodeficient patient presents symptoms of abdominal pain and vomiting. Early endovascular embolization, combined with conservative approaches, effectively alleviated the symptoms in our patient.

Severe anaphylaxis after chimeric antigen receptor T-cell injection: a case report.

Anaphylactic reactions at the time of chimeric antigen receptor T (CAR-T) cell infusion are adverse events that have not been reported in pivotal clinical trials or in real-world series. We report the case of patient with severe anaphylaxis with cardiac arrest after tisagenlecleucel injection for Diffuse Large B cell Lymphoma, who recovered after resuscitation and intensive care treatment; we also conducted a Food and Drug Administration Adverse Event Reporting System database analysis and found several cases of severe anaphlyaxis after CAR-T cell injection. Although not reported in pivotal CAR-T cell studies, anaphylaxis can occur after CAR-T cell injection, highlighting the need to include anaphylaxis as a possible side effect in future studies.

[Allergic asthma in adults: diagnosis and clinical management]. / Asthme allergique de l'adulte: prise en charge.

Asthma is one of the most common chronic diseases in Switzerland. Its prevalence is between 7% and 10% in Western countries and almost half of all asthma patients are sensitized to one or more allergens. It is important to identify this particular group of allergic patients in order to be able to propose a targeted treatment. Due to recent scientific advances, allergologists have gained novel tests to precisely diagnose sensitizations to allergens as well as new treatment options beside allergen avoidance, bronchodilators, topical steroids and desensitization. Here, we summarize the current diagnostic and treatment guidelines for the general practitioner.

Extent of and Reasons for Discontinuation and Nonpublication of Interventional Trials on Connective Tissue Diseases: An Observational Study.

OBJECTIVE: To assess the proportion, the reasons, and the factors associated with the discontinuation or nonpublication of randomized controlled trials (RCTs) on connective tissue diseases (CTDs). METHODS: We searched all interventional RCTs on CTDs registered in ClinicalTrials.gov since 2000. Two reviewers selected studies according to prespecified eligibility criteria. Completion status, publication status, and reported reasons for discontinuation or nonpublication were retrieved on ClinicalTrials.gov, through literature search, and by contacting investigators. Multivariable logistic regression was used to identify factors associated with study noncompletion and nonpublication. RESULTS: We included 175 studies, mostly phase III, placebo-controlled trials on pharmacologic treatments recruiting patients with systemic lupus erythematosus (51%), systemic sclerosis (20%), Sjögren's syndrome (12%), or other CTDs. Fifty-eight (33%) had been discontinued, mainly for insufficient patient accrual, with no differences in discontinuation rates across the CTDs (P > 0.5). Forty-six (35%) of 130 studies having included at least 1 patient were unpublished, and 86 (65%) were published in a peer-reviewed journal after a median of 24 months (interquartile range 15-41) from completion, with a significantly higher publication rate in completed versus discontinued studies (81% versus 22%; P < 0.001). We were able to obtain reasons for nonpublication in one-third of cases. Small sample size (<100 participants) was the only factor associated with study noncompletion and nonpublication. CONCLUSION: One of 3 registered RCTs on CTDs fails to be completed or published. This represents a waste of resources and raises ethical concerns regarding hidden clinical data and unfruitful participation by patients.