RESUMO
Systemic lupus erythematosus (SLE) is an autoimmune disease affecting mostly women of child-bearing age. Immune dysfunction in SLE results from disrupted apoptosis which lead to an unregulated interferon (IFN) stimulation and the production of autoantibodies, leading to immune complex formation, complement activation, and organ damage. Lupus nephritis (LN) is a common and severe complication of SLE, impacting approximately 30% to 40% of SLE patients. Recent studies have demonstrated an alteration in mitochondrial homeostasis in SLE patients. Mitochondrial dysfunction contributes significantly to SLE pathogenesis by enhancing type 1 IFN production through various pathways involving neutrophils, platelets, and T cells. Defective mitophagy, the process of clearing damaged mitochondria, exacerbates this cycle, leading to increased immune dysregulation. In this review, we aim to detail the physiopathological link between mitochondrial dysfunction and disease activity in SLE. Additionally, we will explore the potential role of mitochondria as biomarkers and therapeutic targets in SLE, with a specific focus on LN. In LN, mitochondrial abnormalities are observed in renal cells, correlating with disease progression and renal fibrosis. Studies exploring cell-free mitochondrial DNA as a biomarker in SLE and LN have shown promising but preliminary results, necessitating further validation and standardization. Therapeutically targeting mitochondrial dysfunction in SLE, using drugs like metformin or mTOR inhibitors, shows potential in modulating immune responses and improving clinical outcomes. The interplay between mitochondria, immune dysregulation, and renal involvement in SLE and LN underscores the need for comprehensive research and innovative therapeutic strategies. Understanding mitochondrial dynamics and their impact on immune responses offers promising avenues for developing personalized treatments and non-invasive biomarkers, ultimately improving outcomes for LN patients.
Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Mitocôndrias , Humanos , Nefrite Lúpica/metabolismo , Nefrite Lúpica/patologia , Nefrite Lúpica/imunologia , Nefrite Lúpica/etiologia , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Lúpus Eritematoso Sistêmico/metabolismo , Lúpus Eritematoso Sistêmico/patologia , Lúpus Eritematoso Sistêmico/imunologia , DNA Mitocondrial/metabolismo , Animais , Biomarcadores , MitofagiaRESUMO
BACKGROUND: Most hospitals use electronic health records (EHR) to warn health care professionals of drug hypersensitivity (DH) and other allergies. Indiscriminate recording of patient self-reported allergies may bloat the alert system, leading to unjustified avoidances and increases in health costs. The aim of our study was to analyze hypersensitivities documented in EHR of patients at Lausanne University Hospital (CHUV). METHODS: We conducted a retrospective study on patients admitted at least 24 h to CHUV between 2011 and 2021. After ethical clearance, we obtained anonymized data. Because culprit allergen could be either manually recorded or selected through a list, data was harmonized using a reference allergy database before undergoing statistical analysis. RESULTS: Of 192,444 patients, 16% had at least one allergy referenced. DH constituted 60% of all allergy alerts, mainly beta-lactam antibiotics (BLA) (30%), NSAID (11%) and iodinated contrast media (ICM) (7%). Median age at first hospitalization and hospitalization length were higher in the allergy group. Female to male ratio was 2:1 in the allergic group. Reactions were limited to the skin in half of patients, and consistent with anaphylaxis in 6%. In those deemed allergic to BLA, culprit drug was specified in 19%, 'allergy to penicillin' otherwise. It was impossible to distinguish DH based on history alone or resulting from specialized work-up. CONCLUSIONS: Older age, longer hospital stays, and female sex increase the odds of in-patient allergy documentation. Regarding DH, BLA were referenced in 4% of inpatient records. Specific delabeling programs should be implemented to increase data reliability and patient safety.
Assuntos
Anafilaxia , Hipersensibilidade a Drogas , Humanos , Masculino , Feminino , Registros Eletrônicos de Saúde , Estudos Retrospectivos , Suíça/epidemiologia , Reprodutibilidade dos Testes , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/epidemiologia , Fatores de Risco , Monobactamas , Documentação , Anafilaxia/induzido quimicamente , Antibacterianos/efeitos adversosRESUMO
Systemic lupus erythematosus (SLE) is a complex autoimmune disease affecting various organs and characterized by profound immune disturbances. Monoclonal antibodies such as anifrolumab, targeting type I interferon, and belimumab, targeting a cytokine that activates B-cells and plasmocytes, have shown efficacy in SLE. Voclosporine, a novel calcineurin inhibitor, improves renal outcomes when combined with standard immunosuppression in lupus nephritis. Other approaches like obinutuzumab and CAR-T cells offer hope for refractory patients. These advances diversify SLE management, though their long-term efficacy remains to be established. It is crucial to emphasize basic measures in patients with SLE, including smoking cessation, sun protection, and early use of hydroxychloroquine.
Le lupus érythémateux systémique (LES) est une maladie auto-immune complexe pouvant toucher tous les organes et marquée par des altérations profondes du système immunitaire. De nouvelles thérapies telles que l'anifrolumab, ciblant l'interféron de type I, et le bélimumab, bloquant une cytokine stimulant les cellules B et plasmocytes, ont montré leur efficacité. Un nouvel inhibiteur de la calcineurine, la voclosporine, s'avère utile en adjonction au traitement classique dans la néphrite lupique. D'autres approches comme l'obinutuzumab et les cellules CAR-T sont un espoir pour les cas réfractaires. Ces récentes avancées diversifient la prise en charge du LES mais leur utilité à long terme reste à établir. Rappelons l'importance de mesures de base: arrêt du tabac, protection solaire et utilisation de l'hydroxychloroquine dès le diagnostic.
Assuntos
Doenças Autoimunes , Lúpus Eritematoso Sistêmico , Humanos , Anticorpos Monoclonais/uso terapêutico , Linfócitos B , CitocinasRESUMO
Cellular therapy using genetically modified T lymphocytes expressing synthetic receptors, known as CAR (Chimeric Antigen Receptor), has revolutionized the treatment of certain hematologic malignancies. This success has led to exploring the same approach in the treatment of severe autoimmune diseases refractory to conventional therapies. Initial results in systemic lupus erythematosus have shown complete remissions that appear to persist over time. Consequently, there is a growing number of ongoing clinical trials. In this review, we discuss the rationale behind the use of CAR-T therapies, the targeted autoimmune diseases, and the associated risks.
La thérapie cellulaire à base de lymphocytes T génétiquement modifiés exprimant des récepteurs synthétiques ou CAR (récepteur antigénique chimérique) a révolutionné le traitement de certaines maladies hémato-oncologiques. Ce succès a conduit à l'exploration de la même approche dans le traitement de maladies auto-immunes sévères et réfractaires aux thérapies conventionnelles. Les premiers résultats obtenus dans le lupus érythémateux systémique ont montré des rémissions complètes semblant persister dans le temps. Nous assistons donc actuellement à une prolifération importante d'essais cliniques. Dans cet article, nous abordons le rationnel derrière l'utilisation des thérapies CAR-T, les maladies auto-immunes ciblées, mais aussi les risques associés.
Assuntos
Doenças Autoimunes , Receptores de Antígenos Quiméricos , Humanos , Imunoterapia Adotiva , Doenças Autoimunes/terapia , Terapia Baseada em Transplante de Células e Tecidos , Resposta Patológica CompletaRESUMO
Mixed connective tissue disease (MCTD) is a rare autoimmune condition. Since its first description 50 years ago, its mere existence has been debated, given that it shares features of other autoimmune diseases, such as systemic lupus erythematosus (SLE), systemic sclerosis, inflammatory myopathy, rheumatoid arthritis and Sjogren's syndrome. Also, while antibodies to U1-RNP are essential for the diagnosis of MCTD, these antibodies may be expressed in other circumstances, such as in case of SLE. Nevertheless, the patient fulfilling criteria for MCTD needs specific management. In this review, we describe the clinical features and the potential complications of this complex disease, often wrongly disregarded as benign. We will also emphasize the recommended follow-up exams and address treatment, which is currently lacking formal recommendations.
La connectivite mixte (mixed connective tissue disease (MCTD)) est une maladie auto-immune rare. Dès sa description il y a cinquante ans, l'existence propre de la MCTD est débattue, car les limites avec d'autres maladies, comme le lupus érythémateux systémique (LES), la sclérodermie, les myopathies inflammatoires, la polyarthrite rhumatoïde et le syndrome de Sjögren, sont floues. Les anticorps anti-U1-RNP obligatoires au diagnostic de MCTD sont également exprimés dans d'autres circonstances, comme le LES. Quoi qu'il en soit, le patient présentant des critères de MCTD nécessite une prise en charge spécifique. Nous présentons ici les signes cliniques et complications potentielles d'une maladie longtemps estimée à tort comme d'évolution bénigne. Nous abordons aussi les examens de suivi recommandés et la thérapeutique, qui reste à ce jour mal définie.
Assuntos
Artrite Reumatoide , Doenças Autoimunes , Lúpus Eritematoso Sistêmico , Doença Mista do Tecido Conjuntivo , Humanos , Doença Mista do Tecido Conjuntivo/complicações , Doença Mista do Tecido Conjuntivo/diagnóstico , Doença Mista do Tecido Conjuntivo/terapia , Existencialismo , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/terapia , Doenças RarasRESUMO
The diagnosis of cardiac sarcoidosis, particularly in its isolated cardiac form, represents a major challenge due to non-specific symptoms and the limited sensitivity and specificity of basic cardiac investigations. MRI and metabolic PET-CT are important elements in the diagnostic process. Corticosteroids remain the cornerstone for the treatment of the inflammatory phase, in association with biological agents and steroid-sparing therapies. The goal is to limit the progression of fibrosis, which is a source of malignant arrhythmias and heart failure. The indication for implantation of a cardiac defibrillator must be carefully evaluated to reduce the risk of sudden death. Multidisciplinary collaboration is essential for optimal care.
Le diagnostic de sarcoïdose cardiaque, en particulier dans sa forme cardiaque isolée, représente un défi majeur en raison de symptômes aspécifiques et d'une sensibilité et spécificité limitées des explorations cardiologiques de base. L'IRM et le PET-CT métabolique sont devenus des éléments essentiels dans le processus diagnostique. Les corticostéroïdes restent la pierre angulaire du traitement dans la phase inflammatoire, parallèlement aux agents biologiques et aux thérapies d'épargne cortisonique. L'objectif est d'éviter la progression vers la fibrose, source d'arythmies malignes et d'insuffisance cardiaque. L'indication à l'implantation d'un défibrillateur cardiaque doit être soigneusement évaluée afin de réduire le risque de mort subite. Une collaboration multidisciplinaire est essentielle afin d'assurer une prise en charge optimale.
Assuntos
Insuficiência Cardíaca , Miocardite , Sarcoidose , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Coração , Sarcoidose/diagnóstico , Sarcoidose/terapiaRESUMO
AIMS: To report an exceptional case of nerve infiltration by an otherwise benign chronic B cell leukemia, inducing severe mononeuritis multiplex. METHODS: The patient underwent extensive evaluation, including nerve conduction study and myography, brain and plexus MRI, and nerve biopsy. RESULTS: The clinical and electrophysiological diagnosis was a mononeuritis multiplex with severe motor and sensory involvement; only the nerve biopsy allowed definite diagnosis and introduction of chemotherapy, leading to resolution of sensory deficit and progressive motor improvement. DISCUSSION: Neuroleukemiosis caused by chronic lymphoid leukemia is an exceptional diagnosis. The presence of other possible causes like cryoglobulinemia could induce avoidance of nerve biopsy thus undertreating patient, since steroid treatment is not expected to be efficient on lymphocytic proliferation. Our case stretches the importance of nerve biopsy and raises neuromuscular specialist's awareness of this rare entity.
Assuntos
Leucemia Linfocítica Crônica de Células B , Mononeuropatias , Humanos , Leucemia Linfocítica Crônica de Células B/complicações , Mononeuropatias/diagnóstico , Mononeuropatias/etiologia , Mononeuropatias/tratamento farmacológico , Imageamento por Ressonância Magnética , Biópsia/efeitos adversos , Estudos de Condução NervosaRESUMO
Anti-glomerular basement membrane disease is a rare disease. In its classical presentation it associates rapidly progressive glomerulonephritis and diffuse alveolar hemorrhage, linked to the presence of antibodies targeting type IV collagen in the glomerular and alveolar basal membrane. Anti-GBM disease warrants prompt medical management to limit permanent kidney damage and mortality. Treatment includes plasma exchanges to quickly remove pathogenic antibodies and immunosuppressants to stop their production. This article reviews the pathogenesis and current treatments.
La maladie des anticorps anti-membrane basale glomérulaire (anti-MBG) est une entité rare. Dans sa présentation classique, elle associe une glomérulonéphrite rapidement progressive et une hémorragie alvéolaire diffuse liée à des anticorps dirigés contre le collagène de type IV des membranes basales glomérulaire et alvéolaire. Les pronostics rénal et vital sont engagés. Le traitement doit être prompt et comprend des plasmaphérèses visant à éliminer les anticorps pathogéniques ainsi qu'une immunosuppression destinée à supprimer leur production. Cet article passe en revue la pathogénie et les traitements actuels.
Assuntos
Doença Antimembrana Basal Glomerular , Humanos , Doença Antimembrana Basal Glomerular/diagnóstico , Doença Antimembrana Basal Glomerular/terapia , Autoanticorpos , Hemorragia/etiologia , Imunossupressores/uso terapêuticoRESUMO
Within the group of antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides, granulomatosis with polyangiitis (GPA) is the most frequent. The incidence is around 10 to 20 cases/million/year. Clinical manifestations are varied, with ENT, lungs and kidneys most frequently involved. ANCA are pathogenic by triggering neutrophil activation, which leads to vascular damage. Detection of ANCA is most helpful in establishing the diagnosis, but serology may be negative in GPA limited to the airways. Diagnostic work-up and therapy require a multidisciplinary approach. Treatment includes an induction and maintenance phase, combining corticosteroids and immunosuppressive drugs. It aims at limiting the risk of relapses, which is important in GPA, and at reducing corticosteroids toxicity.
La granulomatose avec polyangéite (GPA) fait partie des vasculites associées aux anticorps anti-cytoplasme des polynucléaires neutrophiles (ANCA). La maladie touche principalement la sphère ORL, les poumons et les reins. Son incidence est de 10 à 20 cas/million/année. Les ANCA sont pathogéniques en induisant une activation des polynucléaires neutrophiles, entraînant des lésions endothéliales. Le diagnostic est facilité par la détection des ANCA, qui peuvent cependant être absents dans les formes ORL limitées. La prise en charge est multidisciplinaire. Le traitement comprend une phase d'induction et une autre de maintien de la rémission, associant corticostéroïdes et immunosuppresseurs. L'objectif du traitement est de limiter le risque important de rechute et de réduire la toxicité des corticostéroïdes.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Granulomatose com Poliangiite , Humanos , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/terapia , Granulomatose com Poliangiite/complicações , Anticorpos Anticitoplasma de Neutrófilos/uso terapêutico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia , Imunossupressores/uso terapêutico , Corticosteroides/uso terapêuticoRESUMO
OBJECTIVES: To characterize patients with positive anti-topoisomerase I (ATA) in lcSSc. METHODS: SSc patients enrolled in the EUSTAR cohort with a disease duration of ≤3 years at database entry were considered. We assessed the risk of major organ involvement in the following groups: ATA-lcSSc vs ACA-lcSSc and vs ANA without specificity (ANA)-lcSSc, and ATA-lcSSc vs ATA-dcSSc. Cox regression models with time-dependent covariates were performed with the following outcomes: new-onset interstitial lung disease (ILD), ILD progression [forced vital capacity (FVC) decline ≥10% and ≥5% vs values at ILD diagnosis), primary myocardial involvement (PMI), pulmonary hypertension (PH), any organ involvement and all-cause mortality. RESULTS: We included 1252 patients [194 ATA-lcSSc (15.5%)], with 7.7 years (s.d. 3.5) of follow-up. ILD risk was higher in ATA-lcSSc vs ACA- and ANA-lcSSc and similar to ATA-dcSSc, although with less frequent restrictive lung disease. The risk of FVC decline ≥10% (35% of ATA-lcSSc) was lower in ATA-lcSSc than in ATA-dcSSc, whereas FVC decline ≥5% occurs similarly between ATA-lcSSc (58% of patients) and other SSc subsets, including ATA-dcSSc. The risk of PMI was similar in ATA-lcSSc and ANA-lcSSc but lower than in ACA-lcSSc; no difference in PH and mortality risk was observed among lcSSc subsets. The risk of any organ involvement, PMI and PH was lower and the mortality tended to be lower in ATA-lcSSc vs ATA-dcSSc. CONCLUSION: ATA-lcSSc patients have a high risk of ILD, albeit with a lower risk of progression compared with ATA-dcSSc, supporting careful screening for ILD in this subgroup.
Assuntos
Hipertensão Pulmonar , Doenças Pulmonares Intersticiais , Esclerodermia Difusa , Esclerodermia Limitada , Escleroderma Sistêmico , Humanos , Esclerodermia Difusa/diagnóstico , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/diagnóstico , Anticorpos Antinucleares , Hipertensão Pulmonar/etiologia , Fenótipo , Escleroderma Sistêmico/diagnósticoRESUMO
BACKGROUND: Up to 20% of patients with moderate to severe Graves' orbitopathy (GO) do not respond to high-dose glucocorticoids (GC). A few studies, including a randomized trial, have demonstrated the efficacy of interleukin-6 (IL-6) blockade with tocilizumab (TCZ) in GC-refractory GO. However, data on predictors of response to TCZ and long-term outcomes are lacking. METHODS: Observational single-center study on ten consecutive patients treated with TCZ for GC-refractory GO, between 2016 and 2020. Median (interquartile range) follow-up was 24 (12-36) months. RESULTS: Inflammation and exophthalmos improved dramatically in all patients within months after starting TCZ. Mean Clinical Activity Score decreased from 4.80 ± 1.13 to 0.70 ± 0.82 points at 6 months (mean change: -4.10 ± 1.52; p < .0001). Proptosis improved from 23.2 ± 2.1 to 20.6 ± 2.0 mm at 6 months (mean change: -2.9 ± 1.4 mm; p < .0001). Diplopia resolved in 7 patients. Thyroid receptor antibodies decreased markedly during TCZ treatment. Baseline serum IL-6 levels did not predict clinical response. TCZ was well-tolerated. During follow-up, 3 patients were diagnosed with cancer (breast cancer in 2 and urothelial cancer in 1). CONCLUSIONS: TCZ was rapidly effective and well-tolerated in our patients with GC-refractory GO. Four patients experienced mild/moderate adverse events as neutropenia, hyperlipidemia, and infections; nearly a third developed cancer during the follow-up. The increased incidence observed could be explained by the high prevalence of smokers, that are at higher risk for Graves' orbitopathy and solid malignancies as breast cancer. Thus, regular cancer screening could be proposed to this vulnerable population receiving high doses of immunosuppressants.
Assuntos
Neoplasias da Mama , Oftalmopatia de Graves , Anticorpos Monoclonais Humanizados , Neoplasias da Mama/tratamento farmacológico , Feminino , Glucocorticoides/uso terapêutico , Oftalmopatia de Graves/patologia , Humanos , Interleucina-6RESUMO
Glucocorticosteroids (GC) remain the mainstay of treatment in most systemic inflammatory diseases. GC have a broad anti-inflammatory action of rapid onset. The downsides of prolonged GC therapy are well established and include infections, osteoporosis and metabolic adverse effects, among others. In systemic sclerosis, GC are associated with an increased risk of scleroderma renal crisis and must be avoided. Adjunction of second-line immunosuppressive drugs may improve disease control and limit GC usage. We summarize here the findings of two studies published in 2021, one reporting the benefits of combining GC with mycophenolate mofetil in immune thrombocytopenia, the other suggesting that blockage of interleukin-6 may decrease disease progression in systemic sclerosis with lung involvement.
Les glucocorticoïdes (GC) demeurent le pilier du traitement de la plupart des maladies inflammatoires systémiques. Ils ont un effet anti-inflammatoire puissant et d'installation rapide. Les effets indésirables des GC sont bien connus : risque infectieux, ostéoporose, diabète et hypertension, entre autres. Dans la sclérose systémique, les GC sont à éviter, car associés à la survenue d'une crise rénale hypertensive. L'adjonction d'immunosuppresseurs comme deuxième ligne de traitement peut améliorer le contrôle de la maladie et limiter l'utilisation des GC. Nous résumons les résultats de deux études récentes, l'une rapportant les bénéfices de l'ajout de mycophénolate mofétil aux GC dans le purpura thrombopénique immun, l'autre suggérant que le blocage de l'interleukine 6 pourrait ralentir la progression de la sclérose systémique (ou sclérodermie) avec atteinte pulmonaire.
Assuntos
Doenças do Sistema Imunitário , Escleroderma Sistêmico , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores , Ácido Micofenólico , Escleroderma Sistêmico/tratamento farmacológicoRESUMO
Anisakis simplex is a parasitic worm. It infects marine mammals that feed on fish and cephalopods, its intermediary hosts. Human disease is caused by accidental ingestion of Anisakis larvae. Upon consumption of contaminated fish, cuttlefish or squid, human may develop two distinct clinical pictures: Anisakiasis is provoked by living larvae penetrating the digestive mucosa. Allergy is caused by IgE-mediate hypersensitivity to living or dead larvae in a previously sensitized individual. Anisakiasis may manifests with violent epi gastric pain, acute abdomen or eosinophilic gastroenteritis. The larvae may be visualized by endoscopy or histology. The main Anisakis allergens are not denaturated by heat or cold and resist to digestion. Allergy diagnosis relies on careful history and detection of specific IgE.
Anisakis simplex est un ver parasite (helminthe) du groupe des nématodes. Il infeste les mammifères marins se nourrissant de poissons et de céphalopodes, ses hôtes intermédiaires. Chez l'homme, l'ingestion de poissons, de calamars ou de seiches contaminés est responsable de 2 tableaux cliniques. L'anisakiase est provoquée par la pénétration de la muqueuse digestive par des larves vivantes. L'allergie est une réaction IgE (immunoglobuline E) médiée aux parasites morts ou vivants chez une personne préalablement sensibilisée. L'anisakiase occasionne des épigastralgies, un abdomen aigu ou de manière plus sournoise une gastroentérite à éosinophiles. Les larves sont visualisables par endoscopie ou à l'histologie. Les principaux allergènes d'Anisakis résistent à la cuisson et à la digestion. Le diagnostic d'allergie se base sur l'anamnèse et la détection d'IgE spécifiques.
Assuntos
Anisaquíase , Anisakis , Hipersensibilidade , Animais , Anisaquíase/diagnóstico , Anisaquíase/epidemiologia , Anisaquíase/parasitologia , Peixes/parasitologia , Humanos , Imunoglobulina E , Larva , Mamíferos , Alimentos Marinhos/efeitos adversos , Alimentos Marinhos/parasitologiaRESUMO
Intravenous iron infusions rarely result in severe hypersensitivity reactions. The primary suspected hypersensitivity mechanism is an abnormal complement activation by non-IgE antibodies to the carbohydrate moieties stabilizing iron formulations. A major risk factor for hypersensitivity reactions is related to the infusion speed. Fishbane-like reactions usually resolve after pausing the infusion, which can be resumed under medical surveillance and at a lower infusion rate. Yet, anaphylactic reactions require emergency first aid and subsequent strict avoidance of intravenous iron. Desensitization protocols can be implemented in selected cases and under strict medical surveillance to reduce the risks of severe reactions upon re-exposure.
L'administration de fer intraveineux (IV) peut rarement se compliquer de réactions d'hypersensibilités sévères, parfois fatales. Le mécanisme supposé est celui d'une activation anormale du complément, possiblement liée à des anticorps non-IgE (immunoglobuline E) dirigés contre les groupements carbohydrates qui stabilisent la formulation de fer. Un débit de perfusion trop rapide est un facteur important de réaction d'hypersensibilité. En effet, les réactions légères se résolvent généralement après mise en pause de la perfusion, qui peut ensuite être reprise à un débit réduit. Les réactions anaphylactiques nécessitent en revanche un traitement d'urgence et une éviction stricte. Le recours à un protocole de désensibilisation sous surveillance médicale étroite permet, dans certaines situations, de limiter le risque de réaction lors d'une réadministration de fer IV.
Assuntos
Anafilaxia , Anemia Ferropriva , Hipersensibilidade a Drogas , Administração Intravenosa , Alergistas , Anafilaxia/induzido quimicamente , Anemia Ferropriva/tratamento farmacológico , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/etiologia , Hipersensibilidade a Drogas/terapia , Humanos , Infusões Intravenosas , Ferro/efeitos adversosRESUMO
Janus kinase inhibitors (JAKi), such as tofacitinib, baricitinib, upadacitinib or ruxolitinib, are small molecules active on specific intracellular targets and used orally for the treatment of autoimmune or myeloproliferative diseases. Their remarkable therapeutic efficacy is offset by a significant risk of toxicities, essentially dose-dependent and a variable pharmacokinetic profile. The JAKi represent a new therapeutic armamentarium for treating autoimmune, myeloproliferative and inflammatory diseases (incl. COVID-19), but require thorough treatment individualization and close monitoring. Therapeutic Drug Monitoring (TDM) of JAKi could allow a personalized prescription and improve the efficacy-toxicity profile.
Les inhibiteurs des Janus kinases (JAKi), tels que le tofacitinib, le baricitinib, l'upadacitinib ou le ruxolitinib, représentent une nouvelle classe de petites molécules actives sur des cibles intra-cellulaires spécifiques, utilisables par voie orale pour traiter des maladies autoimmunes ou néoplasies myéloprolifératives. Leur efficacité thérapeutique remarquable est contrebalancée par un risque significatif de toxicités essentiellement dose-dépendantes et un profil pharmacocinétique variable. Les JAKi constituent une nouvelle arme thérapeutique pour le traitement des maladies autoimmunes, myéloprolifératives et inflammatoires (Covid-19), mais nécessitent une individualisation et un suivi attentifs. Le suivi thérapeutique des médicaments des JAKi pourrait permettre de personnaliser leur prescription et améliorer leur profil efficacité-toxicité.
Assuntos
Artrite Reumatoide , Tratamento Farmacológico da COVID-19 , Inibidores de Janus Quinases , Humanos , Inibidores de Janus Quinases/uso terapêutico , Medicina de Precisão , Artrite Reumatoide/tratamento farmacológicoRESUMO
BACKGROUND: Cardiac arrest is a tragic event that causes 1 death roughly every 90 seconds worldwide. Survivors generally undergo a workup to identify the cause of arrest. However, 5% to 10% of cardiac arrests remain unexplained. Because cardiac arrhythmias underlie most cardiac arrests and increasing evidence strongly supports the involvement of autoantibodies in arrhythmogenesis, a large-panel autoantibody screening was performed in patients with cardiac arrest. METHODS: This is an observational, cross-sectional study of patients from the Montreal Heart Institute hospital cohort, a single-center registry of participants. A peptide microarray was designed to screen for immunoglobulin G targeting epitopes from all known cardiac ion channels with extracellular domains. Plasma samples from 23 patients with unexplained cardiac arrest were compared with those from 22 patients with cardiac arrest cases of ischemic origin and a group of 29 age-, sex-, and body mass index-matched healthy subjects. The false discovery rate, least absolute shrinkage and selection operator logistic regression, and random forest methods were carried out jointly to find significant differential immunoglobulin G responses. RESULTS: The autoantibody against the pore domain of the L-type voltage-gated calcium channel was consistently identified as a biomarker of idiopathic cardiac arrest (P=0.002; false discovery rate, 0.007; classification accuracies ≥0.83). Functional studies on human induced pluripotent stem cell-derived cardiomyocytes demonstrated that the anti-L-type voltage-gated calcium channel immunoglobulin G purified from patients with idiopathic cardiac arrest is proarrhythmogenic by reducing the action potential duration through calcium channel inhibition. CONCLUSIONS: The present report addresses the concept of autoimmunity and cardiac arrest. Hitherto unknown autoantibodies targeting extracellular sequences of cardiac ion channels were detected. Moreover, the study identified an autoantibody signature specific to patients with cardiac arrest.
Assuntos
Autoanticorpos/imunologia , Autoantígenos/imunologia , Canais de Cálcio Tipo L/imunologia , Parada Cardíaca/imunologia , Potenciais de Ação , Adulto , Idoso , Sequência de Aminoácidos , Especificidade de Anticorpos , Arritmias Cardíacas/sangue , Arritmias Cardíacas/imunologia , Arritmias Cardíacas/fisiopatologia , Autoanticorpos/sangue , Biomarcadores , Diferenciação Celular , Células Cultivadas , Estudos Transversais , Feminino , Parada Cardíaca/sangue , Parada Cardíaca/epidemiologia , Sistema de Condução Cardíaco/imunologia , Sistema de Condução Cardíaco/fisiopatologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Células-Tronco Pluripotentes Induzidas/citologia , Canais Iônicos/imunologia , Masculino , Pessoa de Meia-Idade , Miócitos Cardíacos/imunologia , Técnicas de Patch-Clamp , Biblioteca de Peptídeos , Análise Serial de Proteínas , Quebeque/epidemiologia , Sistema de RegistrosRESUMO
OBJECTIVES: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease associated with neuro-psychiatric (NP) manifestations. Frequency and patterns of neuro-psychiatric systemic lupus erythematosus (NPSLE) vary substantially between patients. We conducted a systematic review (SR) of the literature and examined prevalence and characteristics of NPSLE in the Swiss SLE cohort study (SSCS). METHODS: The SR search was performed between January 1999 and January 2020. We included prospective/cross-sectional studies focusing on NPSLE. We secured study characteristics, cohort compositions and frequencies of NP manifestations, assessed heterogeneity across reports and investigated sources of variation using meta-regression models. Regarding the SSCS, we reviewed all patients included and classified NP manifestations. RESULTS: The SR searches identified 530 studies. We included 22 studies in our meta-analysis, the mean frequency of NPSLE ranged from 10.6% to 96.4%. The frequency of NPSLE in the SSCS was 28.1%. Severe events including cerebrovascular insults, seizures and psychosis appeared in 7.1%, 5.3% and 6.5% respectively. There was a linear relationship between duration of SLE and cumulative incidence of NPSLE. CONCLUSIONS: The spectrum of NPSLE is very broad. The diagnostic work-up and rates of reported manifestations varied substantially across studies. We call for concerted efforts and consensus regarding definitions of NPSLE that will facilitate accurate diagnosis and attribution to SLE, particularly with a view to timely intervention and patient outcomes.
Assuntos
Lúpus Eritematoso Discoide , Lúpus Eritematoso Sistêmico , Vasculite Associada ao Lúpus do Sistema Nervoso Central , Estudos de Coortes , Estudos Transversais , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/epidemiologia , Vasculite Associada ao Lúpus do Sistema Nervoso Central/epidemiologia , Estudos Prospectivos , Suíça/epidemiologiaRESUMO
Sjögren's syndrome (SS) is an auto-immune condition involving salivary and lacrymal glands leading to dry mouth and dry eyes symptoms. Some patients also present with systemic manifestations. Diagnosis of SS is made after clinical, serological, and histological assessment according to the American College of Rheumatology and European League Against Rheumatism (EULAR) classification criteria. Recent clinical trials showed a significant decrease of systemic activity of SS in patients treated with iscalimab (anti-CD40) and ianalumab (anti-BAFF-R). These results need to be confirmed in larger studies. However, two phase 3 randomized trials did not show efficacy treating SS with abatacept. We also describe in this article the first EULAR recommendations on SS management.
Le syndrome de Sjögren (SS) est une pathologie autoimmune se présentant habituellement par une sécheresse oculo-buccale ou par des manifestations systémiques de présentation variable. Le diagnostic se base sur des éléments cliniques, biologiques et histologiques selon les critères définis par l'American College of Rheumatology et l'European League Against Rheumatism (EULAR). Sur le plan thérapeutique, des études cliniques récentes ont montré l'efficacité de nouvelles molécules comme l'iscalimab (anti-CD40) ou l'ianalumab (anti-BAFF-R) sur l'atteinte systémique du SS, qui devra être confirmée dans de plus grandes études. Deux études de phase 3 n'ont en revanche pas pu démontrer l'efficacité de l'abatacept. L'EULAR a publié les premières recommandations européennes de prise en charge du SS que nous décrivons dans cet article.
Assuntos
Reumatologia , Síndrome de Sjogren , Anticorpos Monoclonais Humanizados , Humanos , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/tratamento farmacológico , Estados UnidosRESUMO
Asthma is a chronic disease and asthma control can be affected by many factors. In case of difficult asthma, intensifying drug therapy is not the key. This type of asthma needs an overall management in order to diagnose and treat each factor known to be associated with poor asthma control. The aim of this article is to describe the structured and systematic approach for these patients.
L'asthme est une maladie chronique dont le contrôle peut être influencé par de nombreux facteurs. Ainsi, en cas d'asthme difficile, l'intensification du traitement médicamenteux n'est pas la seule clé. Ces formes d'asthme nécessitent une prise en charge globale afin de dépister et de prendre en charge l'ensemble des cofacteurs pouvant expliquer le mauvais contrôle. L'objectif de cet article est de décrire la démarche systématisée et multidisciplinaire nécessaire à la prise en charge de ces patients.
Assuntos
Asma , Asma/diagnóstico , Asma/tratamento farmacológico , Doença Crônica , HumanosRESUMO
Cannabis-fruit and vegetable syndrome is of recent discovery and linked to lipid transfer protein (LTP) sensitization. It is thought that the primary sensitization originates from the cannabis LTP (Can s 3). Sensitized patients can cross-react to others LTP homologs such as peach LTP (Pru p 3). Diagnosis may be challenging, as consumption of cannabis is often omitted by the patient and needs to be specifically addressed during the interview. Thus, meticulous history taking is mandatory. Laboratory workup includes LTP-specific IgE and skin testing. Management relies on allergen eviction.
Le syndrome cannabis-fruits et légumes est une forme d'allergie croisée récemment découverte et semble liée à une sensibilisation aux protéines de transfert lipidique (LTP, Lipid Transfer Protein). Il est supposé que la sensibilisation primaire intervienne par la LTP du cannabis. Les sujets sensibilisés sont ensuite à risque de réagir à d'autres LTP, comme celle de la pêche, mais pas uniquement. Le diagnostic est souvent fastidieux du fait de la méconnaissance de cette entité par le clinicien et de la réticence des patients à parler de leur consommation de cannabis. Le diagnostic repose sur une anamnèse détaillée, des tests cutanés avec les allergènes suspectés et la recherche d'immunoglobulines E spécifiques contre les LTP. Le traitement consiste en l'éviction du cannabis et des fruits et légumes responsables de symptômes.