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Troubles mnésiques et difficultés attentionnelles sont fréquemment rapportés par les patients présentant un syndrome de Gougerot-Sjögren (SGS). Ces plaintes neuropsychiatriques sont difficilement objectivables par les soignants [1]. Nous décrivons ici les atteintes cognitives et la qualité de vie de patients avec SGS, afin de décrire le « profil » neuro-psychologique présenté par ces patients. De janvier 2017 à janvier 2019, les patients suivis pour un SGS au CHU de Montpellier et rapportant des symptômes cognitifs lors de leur consultation de suivi ont été évalués par le Centre Mémoire de Ressources et de Recherche (CMRR). Etaient alors évaluées : les plaintes cognitives (Questionnaire de Plainte Cognitive [QPC] et Auto-évaluation de la plainte mnésique [AEPM]) ; les fonctions cognitives objectives [MMSE [Mini Mental State], Grober [test de rappel immédiat et de rappel différé de 16 mots], Epreuve du Code [WAIS] ; des éléments de dépression et d'anxiété (Beck Depression Inventory [BDI], State Trait Inventory Anxiety [STAI]) ; la qualité de vie (SF-36). Le tableau clinico-biologique classique de la maladie et son activité (ESSPRI et ESSDAI) ont été recueillis en parallèle. Le projet a été validé au comité local d'éthique (2018_IRB-MTP_06-08). Les évaluations cognitives ont été comparées aux normes actuelles [2]. Au total, 35 patients (33 femmes et 2 hommes) avec SGS selon les critères de l'ACR/EULAR ont pu être évalués dans le cadre du soin. L'âge médian était de 57 ans [38–81], avec une durée moyenne d'évolution de la maladie de 7 ans [2–38]. Il y avait 7 SGS secondaires (20 %), associés à un lupus érythémateux disséminé dans 5 cas. Le score moyen de l'ESSDAI était de 2,85 [0–13], et celui de l'ESSPRI de 6,21 [2,66–9,00]. Sur le plan cognitif, le QPC était considéré comme anormal pour 80,6 % (25/31) des patients et l'AEPM pour 61,8 % (21/34). En comparaison aux résultats obtenus pour une population de sujets sains appariés sur l'âge, le sexe et le niveau socioculturel (Cohorte Constances, [2]), nos patients présentaient des scores inférieurs au 10ème percentile pour 29,4 % (10/34) d'entre eux concernant le MMSE, 20,6 % (7/34) pour le test de Grober, et 35,3 % (12/34) pour la WAIS. Les fonctions visuo-spatiales étaient altérées pour 9,1 % des patients (3/33) (figure de Rey) et pour 6,1 % (2/33) selon le test de la VOSP (Visual Object and Space Perception). Les scores des 8 domaines de la SF 36 (physical function, role physical, bodily pain, general health, vitality, social function, role emotional, mental health) étaient inférieurs aux scores moyens d'une population générale. Quinze sujets (45,5 %) présentaient une thymie triste (BDI), et 26 (81,3 %) avaient un trait anxieux (STAI). Les altérations de la qualité de vie (SF36) n'étaient pas corrélés aux mesures d'activité de la maladie (ESSDAI ou ESSPRI). Nos résultats objectivent une atteinte cognitive avec des troubles de mémoire épisodique et des fonctions d'encodage et de récupération (Grober), mais aussi des anomalies de vitesse de traitement (Epreuve de WAIS) chez un nombre significatif de patients avec SGS issus d'une population suivie en routine, en comparaison avec une population témoin appariée sur l'âge, le sexe et le niveau socioculturel. On observe cependant une discordance entre le ressenti du trouble (QPC, AEPM) et les éléments objectifs obtenus par les tests neuropsychologiques. Ces constatations préliminaires peuvent conduire à explorer précisément les plaintes neuro-cognitives des patients, et engagent à des études approfondies afin d'appréhender les mécanismes anatomo-immunologiques pouvant aboutir à ces dysfonctionnements impactant la qualité de vie, mais aussi la relation médecin-malade et donc la prise en charge de ces malades. [ABSTRACT FROM AUTHOR]

Alors que l'anxiété et les symptômes dépressifs peuvent prendre une grande place dans le syndrome de Gougerot–Sjögren (SGS), les plaintes mnésiques et attentionnelles sont fréquentes mais mal objectivées. Notre travail décrit les anomalies d'imageries cérébrales chez des patients suivis pour un SGS, et recherche des associations avec les plaintes fonctionnelles et avec les résultats de tests neurocognitifs validés. Au CHRU de Montpellier, entre janvier 2017 à janvier 2019, des patients suivis en médecine interne pour un SGS et rapportant des symptômes cognitifs, ont pu bénéficier d'une IRM cérébrale (acquisition 3D pondérée T1 et 3D Flair) dans le cadre du soin, avec évaluation volumétriques des structures cérébrales par segmentation volumique à partir de la séquence 3DT1 MPRAGE qui a été réalisée en utilisant l'algorithme Morphobox [1]. En parallèle, une évaluation cognitive a pu être réalisée par le Centre Mémoire de Ressources et de Recherche (CMRR) (MMSE [Mini Mental State], Grober [test de rappel immédiat et de rappel différé de 16 mots], et Epreuve du Code [WAIS] notamment). Une auto-évaluation cognitive (Questionnaire de Plainte Cognitive [QPC] et de la plainte mnésique [AEPM]) ont pu aussi être recueillies. Les éléments cliniques et biologiques de la maladie, ainsi que son activité (ESSPRI et ESSDAI) ont été relevés. Comité local d'éthique (2018_IRB-MTP_06-08). Au total, 23 patients (22 femmes et 1 homme) ont pu bénéficier d'une IRM cérébrale. L'âge médian était de 53 ans [38–81] avec une durée médiane d'évolution de la maladie de 7 ans [2–38]. Le score moyen de l'ESSDAI était de 3,30 [0–13], et celui de l'ESSPRI de 6,54 [2,97–9]. Les IRM cérébrales ont montré des hypersignaux aspécifiques de la substance blanche (classification Fazekas) pour 64,3 % des patients analysés (9/14). En comparaison aux données volumétriques de référence d'une population saine appariée sur l'âge et le sexe, 52,1 % (12/23) des patients avec SGS présentaient une baisse de volume de certaines structures cérébrales : LCR (18,2 %, n = 22) ; corps calleux (13,6 %, n = 22) ; substance blanche profonde (9,1 %, n = 22) ; substance grise des lobes frontaux (9,1 %, n = 22). Pour 95,7 % (22/23) de ces patients, le volume de l'hippocampe était considéré comme normal. Des analyses complémentaires des données d'imagerie sont encore en cours. Chez ces patients, une altération objective des fonctions cognitives [vitesse de traitement de l'information (WAIS), perception visuo-spatiale (VOSP, Figure de Rey), du langage (DO 80) et de la mémoire (Grober)] a été mise en évidence, en comparaison aux résultats obtenus pour des sujets sains appariés sur l'âge, le sexe et le niveau socioculturel (Cohorte Constances [2]). Dans ce travail, sous réserve des analyses complémentaires en cours, plus de la moitié des patients présentant un SGS présenteraient des anomalies volumétriques à l'IRM cérébrales. L'hippocampe semble ici conserver un volume normal tandis que le corps calleux, responsable de la communication inter-hémisphérique, pourrait être atrophié. Nous retrouvons par ailleurs la fréquence élevée (déjà décrite dans la littérature) des hypersignaux de la substance blanche (malgré l'absence de facteurs de risque cardio-vasculaires patents). Ces résultats préliminaires suggèrent l'existence de variations volumétriques des structures cérébrales chez les patients atteints de SGS et rapportant des symptômes cognitifs, ceux-là même présentant des altérations subjectives et objectives cognitives. Ces données préliminaires nous incitent à compléter nos travaux par l'analyse des données d'imagerie fonctionnelle, permettant d'intégrer le fonctionnement et la connectivité cérébrale. Ceci pourrait permettre de mieux appréhender les mécanismes menant aux symptômes neurocognitifs au cours du SGS. [ABSTRACT FROM AUTHOR]

Les infections impactent la mortalité des patients avec syndrome de Gougerot-Sjögren primaire (SGSp). Notre étude rétrospective unicentrique visait à décrire les infections survenues au sein d'une population de patients avec SGSp hospitalisés au CHU, ainsi que les caractéristiques de leur maladie. Les patients présentant un SGS ont été sélectionnés aléatoirement par l'intermédiaire du codage PMSI du CHU, entre 2009 et 2018. Après analyse exhaustive des dossiers, seuls les patients avec SGSp et respectant les critères ACR/EULAR 2016 ont été inclus. Les caractéristiques cliniques, biologiques et histologiques du syndrome de Gougerot-Sjögren, ainsi que les caractéristiques des infections survenues au cours de la maladie, ont été recueillies. Nous avons comparé les caractéristiques du syndrome de Gougerot-Sjögren selon la présence d'infection en hospitalisation. Cent neuf patients avec SGSp ont été inclus (93 % de femmes, âge moyen 53,6 ± 14,3 ans, durée moyenne de suivi de 8,2 ± 8,4 ans). Cinquante et un pour cent des patients avaient reçu de l'hydroxychloroquine. Au total, 78 épisodes infectieux ont été rapportés chez 47 (43 %) patients. On dénombrait 25 infections en hospitalisation chez 20 (18 %) patients, de causes urinaires (28 %), pulmonaires (24 %), ORL (16 %) et digestives (12 %). Ces patients avec infections en hospitalisation étaient plus âgés au diagnostic, avec plus d'hypocomplémentémie, moins de prise d'HCQ, sans différence de traitements immunomodulateurs. L'impact de l'hydroxychloroquine sur le risque infectieux nécessite plus d'investigations. Vaccination et lutte contre le syndrome sec pourraient être bénéfiques. Infections are responsible for a part of the overall mortality in primary Sjögren's syndrome patients (pSS). Our retrospective monocentric study aimed at describing infections reported in a population of pSS hospitalized patients, along with the characteristics of their disease. Patients with SS have been randomly selected from our hospital database claim, between 2009 and 2018. After careful analysis of their medical chart, only patients with pSS and fulfilling ACR/EULAR 2016 diagnosis criteria were included. We collected main clinical, biological and pathological characteristics of SS, along with all the reported infections during the follow-up. The characteristics of the disease were compared according to the presence of an infection in hospitalization. In total, 109 pSS patients were included (93% of women, mean age 53.6 ± 14.3 years, mean follow-up 8.2 ± 8.4 years). Fifty-one percent had been exposed to hydroxychloroquine (HCQ). Seventy-eight infections were recorded in 47 (43%) patients. Twenty-five infections were recorded in hospitalization (5 in critical care) in 20 (18%) patients, whom leading causes were urinary tract (28%), pulmonary (24%), ENT (16%), and intestinal (12%) infections. pSS patients with infections in hospitalization were older, exhibited more hypocomplementemia, and were less exposed to HCQ. We found no difference in immunosuppressive treatments exposure. The impact of HCQ exposure on infectious risk needs further investigations. Broad vaccination campaign and tight control of sicca syndrome could lead to a better control of infection risk. [ABSTRACT FROM AUTHOR]

L'hémophilie acquise est une maladie auto-immune exceptionnelle. Le traitement immunosuppresseur a pour objectif d'enrayer la production d'autoanticorps inhibiteurs des facteurs VIII (FVIII) ou IX (FIX) de la coagulation. Une association corticothérapie-cyclophosphamide est recommandée en première intention. À partir de notre expérience au CHU de Nîmes, nous discutons la place du rituximab dans l'arsenal thérapeutique. Nous rapportons une étude observationnelle monocentrique rétrospective. Nos données sont discutées à la lumière des données de la littérature, en particulier des cohortes EACH2 et SACHA. Huit patients dont 7 avec un anticorps anti-FVIII ont été consécutivement inclus à partir de 2005. L'âge moyen était de 68,5 ans avec une prédominance masculine (62,5 %). Les manifestations hémorragiques étaient habituellement spontanées et superficielles. Une pathologie, notamment auto-immune ou néoplasique, était associée chez 5 des 8 patients. Un traitement hémostatique dit « by-passant » était prescrit pour 3 patients. Du rituximab était prescrit pour 5 patients, dont trois fois en première intention, et toujours associé à la corticothérapie. Trois patients ont reçu une association cyclophosphamide/cortisone, deux ont été traités exclusivement par une corticothérapie orale. La rémission était obtenue chez tous les patients, sans rechute ultérieure. Le délai moyen pour obtenir la rémission sous rituximab (après la première injection) était de 32,5 jours (10–143). Les résultats observés dans notre série de patients sont cohérents avec les données de la littérature. Le rituximab semble être un traitement efficace et bien toléré de l'hémophilie acquise auto-immune. Sa place reste cependant à préciser. Autoimmune acquired haemophilia is a rare autoimmune disease. The purpose of immunosuppressive therapy is to stop the production of autoantibodies that inhibit clotting factors VIII or IX. A corticosteroids-cyclophosphamide combination is recommanded as first-line therapy. From our experience at the University Hospital of Nîmes, we discuss the place of rituximab in the therapeutic arsenal. We report a monocentric observational retrospective study. Our data are discussed in light of literature data, in particular cohorts EACH2 and SACHA. Eight patients (7 with FVIII anibodies) were consecutively included from 2005. The average age was 68.5 years with a male predominance (62.5%). Bleeding manifestations were usually spontaneous and superficial. A pathology, mostly autoimmune or neoplastic, was associated in 5/8 patients. A "by-pass" haemostatic treatment was prescribed for 3/8 patients. Rituximab was prescribed for 5/8 patients, three times as first-line therapy, and always associated with corticosteroids. Three patients received a cyclophosphamid/cortisone combination, two were treated exclusively with oral corticosteroids. Remission was obtained in all patients, without subsequent relapse. The average time to obtain remission under rituximab (after the first injection) was 32.5 days (10–143). The results observed in our series of patients are consistent with the data from the literature. Rituximab appears to be an effective and well-tolerated treatment for autoimmune acquired haemophilia. However, its place remains to be specified. [ABSTRACT FROM AUTHOR]

La maladie de Rendu-Osler est une génopathie vasculaire rare associant épistaxis, télangiectasies, antécédents familiaux de Rendu-Osler et parfois des malformations vasculaires viscérales. Les malformations artério-veineuses pulmonaires (MAVP) peuvent se compliquer d'accidents vasculaires et d'abcès cérébraux ou d'hypoxie. De ce fait, elles doivent être embolisées dès que possible. Les recommandations pour le suivi des MAVP proposent de réaliser un scanner thoracique tous les 5 ans afin de détecter les malformations accessibles à une embolisation exposant les patients à un taux de radiations ionisantes cumulées non négligeable. Déterminer la prévalence des MAVP et l'incidence des nouvelles MAVP chez les patients Rendu-Osler indemnes initialement. Chez les patients avec des MAVP au diagnostic, observer leur évolution radiologique au cours du temps et décrire les évènements neurologiques afin de proposer un intervalle de suivi adapté. Les données cliniques et d'imagerie ont été recueillies de manière rétrospective pour les patients avec maladie de Rendu-Osler certaine (critères de Curaçao) pris en charge dans le centre de compétence Rendu-Osler sur la période de 2005 à août 2019. Parmi les patients ayant des MAVP, nous avons analysé les données des patients pour lesquels 2 scanners thoraciques étaient disponibles avec un intervalle de temps d'au moins à 5 ans. Les scanners ont été revus par le même radiologue expérimenté. Pour chaque malformation, nous avons recueilli sa localisation, son type (simple, complexe, microscopique ou multiples s'il existait de multiples MAVP microscopiques et dans plusieurs lobes pulmonaires), la taille du diamètre de l'artère afférente, la taille du sac, si elle a été embolisée, l'efficience de l'embolisation à au moins 5 ans. Les évènements neurologiques au cours du suivi ont été analysés. Deux cent soixante et un patients atteints de la maladie de Rendu-Osler (147 femmes et 114 hommes) ont pu être analysés. L'âge moyen au 1er scanner thoracique était de 43,8 ans. La prévalence des MAVP dans la cohorte était de 36,4 %. Dans le groupe sans MAVP au scanner initial (n = 166), l'incidence de MAVP était de 11 cas pour 100 personnes années sur 10 ans, soit 10 nouvelles MAVP. Parmi celles-ci, une seule avait les critères pour l'embolisation. Dans le groupe avec MAVP au scanner initial (n = 95), seulement 5 nouvelles MAVP sont apparues, dont 2 avaient les critères pour l'embolisation. Le suivi sur plus de 5 ans était disponible pour 41 d'entre eux (2 scanners à plus de 5 ans d'intervalle) correspondant à 149 MAVP. Vingt-sept avaient été embolisées avant le 1er scanner disponible, 40 étaient simples (une seule artère afférente), 11 complexes (plusieurs afférences), 40 micro-MAVP et 31 multiples. Sur les 149 MAVP, 78 avaient les critères d'embolisation, et 45 (57,6 %) ont été embolisées. Six MAVP déjà embolisées précédemment ont été ré-embolisées (60 %), 29 sur les 40 simples (72,5 %), 8 sur les 11 complexes (72,7 %). Deux micro-MAVP ont été embolisées. Durant un suivi moyen de 10 ans, une MAVP sur les 6 précédemment embolisées s'est recanalisée. Sept MAVP complexes sur 8 embolisées se sont recanalisées (87,5 %). Treize MAVP simples se sont recanalisées parmi les 29 embolisées 44,8 %. Les 2 micro-MAVP embolisées ne se reperméabilisaient pas en 10 ans. Parmi les MAVP non embolisées, (n = 87) nous avons observé une augmentation en taille de seulement 2 micro-MAVP, mais n'avait les critères requis pour une embolisation. Les MAVP multiples n'ont pas été embolisées et aucune n'a grossi ni n'a obtenu les critères d'embolisation en 10 ans. En analyse multivariée selon la présence ou non de MAVP initiale, il n'y a aucune différence significative entre la probabilité d'avoir un AIT, AVC ou abcès cérébral. Le faible risque évolutif des MAVP, l'absence de majoration du risque neurologique après une prise en charge adaptée, plaident pour rediscuter les recommandations : un scanner thoracique de suivi tous les 10 ans semble suffisant. Ces données devront être confirmées sur un plus grand nombre de patients. [ABSTRACT FROM AUTHOR]

Les liens entre artérite à cellules géantes (ACG), pseudo-polyarthrite rhizomélique (PPR) et cancer sont complexes, et les études épidémiologiques d'incidence ne retrouvent que de manière inconstante une association entre ces pathologies. L'objectif de cette étude était de décrire le profil des patients atteints d'ACG et/ou de PPR et de cancer, sur le plan clinique, histologique et en terme d'évolutivité. Les patients atteints d'ACG et/ou de PPR ayant développé une tumeur maligne solide, pris en charge au CHU de Montpellier entre 1996 et 2017 ont été identifiés à l'aide du codage du Programme de Médicalisation des Systèmes d'Information (PMSI). Pour être inclus, les patients devaient avoir un diagnostic vérifié d'ACG (selon les critères ACR 1990, avec ajout d'un critère de vascularite des gros vaisseaux à l'imagerie) ou de PPR (selon les critères de l'EULAR 2012), et devaient avoir une confirmation histologique de leur cancer. Les données recueillies concernaient les caractéristiques démographiques, cliniques, paracliniques, les traitements introduits, ainsi que des données de temporalité (dates de survenue et de rechutes) pour la pathologie inflammatoire et le cancer. Les caractéristiques histologiques des tumeurs (infiltrat inflammatoire, nécrose) ont été étudiées par relecture des lames de biopsie ou de résection, par un seul anatomopathologiste en aveugle des compte rendus, et de manière standardisée. En cas de cancers multiples chez un même patient, seul le cancer le plus proche chronologiquement de la maladie inflammatoire était considéré pour l'analyse. L'identification des facteurs déterminant la présence d'inflammation ou de nécrose au niveau de l'histologie du cancer, ainsi que des paramètres augmentant le risque d'évolution défavorable, était réalisée à l'aide de tests non paramétriques (test de Wilcoxon). Les caractéristiques des patients étaient également comparées à celles d'une population témoin atteinte d'ACG et/ou PPR et exempte de cancer. Trente-six patients atteints de cancer et d'ACG et/ou de PPR étaient inclus dans l'étude. Les caractéristiques cliniques et paracliniques de la maladie inflammatoire étaient comparables à celles de la cohorte avec ACG et/ou PPR sans cancer. Les néoplasies étaient majoritairement urologiques (13 cas, 36,1 %), digestives (7 cas, 19,4 %), cutanées (6 cas, 16,7 %) et gynécologiques (6 cas, 16,7 %), le plus souvent sans localisation secondaire (26 cas, 72,2 %). Dans 16 cas (44,4 %), le cancer survenait dans l'année du diagnostic d'ACG/PPR. Sur les 33 prélèvements disponibles pour l'analyse histologique, 25 prélèvements ne présentaient pas ou peu d'inflammation (75,8 %), et 8 (24,2 %) présentaient un infiltrat inflammatoire modéré à intense. Une nécrose tumorale était observée dans 11 cas soit 33,3 %. Les analyses ne montraient pas d'association entre l'histologie des cancers (inflammation, nécrose) et les caractéristiques de la maladie inflammatoire (ACG ou PPR, positivité de la biopsie d'artère temporale, simultanéité de survenue). Par contre, la présence d'une corticothérapie au moment du diagnostic de cancer semblait associée à une part moins importante de nécrose (p = 0,02), sans différence significative en terme d'inflammation. Sur le plan de l'évolutivité, la présence d'une rechute de l'ACG ou de la PPR était associée à une évolution moins souvent défavorable (d'emblée ou rechute) du cancer (p = 0,02). Le lien épidémiologique entre ACG et/ou PPR et cancer est incertain, mais il pourrait y avoir une intrication des mécanismes de développement de ces pathologies. La survenue quasi exclusive de ces maladies inflammatoires après 50 ans, la possible relation de temporalité avec le cancer (avec une relation négative sur la rechute), et la découverte d'une dysfonction du checkpoint PD1-PDL1 dans la physiopathologie de l'ACG [1] (checkpoint également impliqué dans la carcinogénèse) pourraient être des arguments en faveur de ce concept. Il existe une potentielle relation de temporalité entre ACG/PPR et cancer, même si le caractère rétrospectif et le petit effectif de l'étude actuelle ne permettent de l'affirmer. En revanche, la présence et l'intensité de l'ACG ou de la PPR au moment du diagnostic de cancer ne semblent pas avoir d'impact sur les remaniements locaux inflammatoires ou nécrotiques tumoraux. [ABSTRACT FROM AUTHOR]

La maladie fibrosclérosante à IgG4 (MAG4) se manifeste par une atteinte multi-organique avec une élévation des IgG4 sériques et des caractéristiques histologiques communes : un infiltrat lymphocytaire à IgG4 associé à une fibrose et des veinulites. La pancréatite auto-immune (PAI) est une des atteintes les plus fréquentes. En cas de forme pseudotumorale, il est parfois difficile de faire la distinction entre une PAI et un cancer du pancréas (CP) qui reste le diagnostic à évoquer en priorité étant donné la gravité du pronostic. Les recommandations en la matière attestent qu'il n'est pas nécessaire d'obtenir la preuve histologique avant chirurgie si la maladie est résécable d'emblée en présence d'une imagerie typique. Or, la distinction en imagerie entre un CP et une PAI à IgG4 est particulièrement difficile. A contrario, une résection chirurgicale est inutile en cas de MAG4, pathologie réputée corticosensible. Nous rapportons ici le cas de deux patients ayant subi une duodénopancréatectomie céphalique (DPC) pour suspicion de CP, qui s'est finalement révélé être une PAI de type 1 (MAG4). Premier cas : en juin 2009, la présence de diarrhées graisseuses, avec perte de 16 kg et diabète de novo révélaient chez un homme de 56 ans aux antécédents de maladie de Hodgkin une dilatation bi canalaire intrahépatique et du cholédoque responsable de perturbations du bilan hépatique (ASAT 3 N, ALAT 3 N, GGT 30 N PAL N). La bili IRM notait une plage suspecte au niveau de la tête du pancréas de 8 mm et l'écho endoscopie confirmait le caractère compressif de la lésion. La biopsie trans-duodénale montrait la présence de rares cellules épithéliales atypiques. Dans ce contexte une DPC associée à une lobectomie hépatique gauche était réalisée. L'aspect peropératoire était celui d'un pancréas induré et atrophique avec réactions inflammatoires majeures sans tumeur individualisable. La lobectomie hépatique gauche première avec examen extemporané n'était pas en faveur d'une métastase permettant la DPC. L'analyse histologique définitive était en faveur d'une pancréatite auto-immune sclérosante lymphoplasmocytaire, avec infiltration par des plasmocytes à IgG4. Sans aucun traitement adjuvant, le patient est resté en rémission jusqu'aujourd'hui. Deuxième cas : un homme de 74 ans est admis aux urgences en juin 2017 pour fébricule et douleur à l'hypochondre droit. La biologie montrait une cytolyse et cholestase ictérique (ASAT 3 N, ALAT 5 N, GGT 9 N, PAL 3 N, bilirubine conjuguée à 9 N), avec une CRP à 42 mg/L. Les sérologies virales et le bilan auto-immun étaient négatifs. Le scanner puis l'IRM révélaient une tumeur de la tête du pancréas en faveur d'un adénocarcinome. Le cytobrossage montrait la présence de cellules atypiques de dysplasie de haut grade et le carcinom antigen 19-9 (CA19-9) était à 3000 UI/mL (N < 37U/mL). Dans ce contexte, une chimiothérapie néo-adjuvante par FOLFIRINOX a été décidée en réunion de concertation. La réévaluation après 8 cycles montrait une amélioration du bilan hépatique, une normalisation du Ca19-9 et la disparition de la masse pancréatique. Devant la bonne réponse à la chimiothérapie, une DPC était réalisée. Les résultats anatomopathologiques définitifs montraient l'absence de malignité, mais révélaient un infiltrat lymphoplasmocytaire avec fibrose avec en immunohistochimie une positivité de l'anticorps anti-IgG4 révélant compatible avec une pancréatite et cholangite à IgG4. Le patient a bénéficié d'une corticothérapie systémique adjuvante, avec une rémission maintenue de la MAG4 jusqu'aujourd'hui. La PAI à IgG4 doit être considérée comme un diagnostic différentiel devant tout syndrome de masse du pancréas. Nos observations illustrent la grande difficulté de ce diagnostic, en particulier lorsqu'un faisceau d'arguments renforce l'hypothèse néoplasique (imagerie, cytologie). Dans le cadre des tumeurs pancréatiques, une révision des algorithmes diagnostiques intégrant l'éventualité d'une MAG4 nous semble nécessaire. [ABSTRACT FROM AUTHOR]

Peu d'études ont analysé les caractéristiques et traitements des thrombopénies immunologiques cliniquement significatives (TICS) secondaires au lupus érythémateux systémique (LES). Étude observationnelle rétrospective multicentrique, basée sur un appel à observations au sein des centres de médecine interne des régions Centre-Est et Sud incluant des adultes avec LES (critères ACR 1997 et SLICC 2012), thrombopénie < 30 G/L et manifestations hémorragiques pris en charge entre 2000 et 2018. Les thrombopénies non attribuables au LES étaient exclues. La gravité des événements hémorragiques (EH) était évaluée par les scores OMS et de Khellaf et al. [1] , l'activité du LES par le SLEDAI. Un score OMS > 2 ou Khellaf > 8 définissait les EH majeurs (EHM). Les immunosuppresseurs conventionnels (IS), le rituximab (RTX), et les agonistes des récepteurs de la thrombopoïétine (aRTPO) étaient définis comme traitements spécifiques (TS) et la réponse (R) de la TICS selon le consensus [2]. Les variables qualitatives étaient comparées selon le Test de Fisher, la non-significativité (NS) définie par p > 0,05. Soixante-quatorze patients ont été inclus dont 65 femmes (88 %). L'âge médian au diagnostic était de 28 ans et la durée de suivi médiane de 83 mois. Le diagnostic de TI précédait celui de LES dans 18 cas (24 %), était concomitant dans 35 cas (47 %), et postérieur dans 19 cas (26 %). Au diagnostic de LES 70 patients présentaient des symptômes cutanéo-articulaires, 11 des sérites, 9 une néphropathie lupique, 7 un neurolupus, 3 une anémie hémolytique auto-immune (AHAI), 1 érythroblastopénie ; 47 malades (64 %) présentaient des anticorps antiphospholipides (APL), 11 un syndrome des APL. Au total, 179 EH étaient répertoriés, 37 révélaient la TI (50 % des patients). Dix-neuf patients (26 %) présentaient ≥ 1 EHM. Ce « groupe EHM » présentait plus d'EH cumulés (5,4 vs 1,4/patient), un LES plus actif (SLEDAI moyen : 8 vs 5,7) et des sérites (32 % vs 9 % ; p = 0,027), une moindre prévalence d'APL (42 % vs 70 % ; p = 0,03), et un recours transfusionnel plus fréquent (p = 0,02). Il cumulait aussi la moitié des transfusions (8/16) et la majorité des hospitalisations (288/388, 61 %) réalisées. Tous recevaient une corticothérapie, 71 de l'hydroxychloroquine, et 34 ≥ 1 IS : azathioprine chez 21 (13 R) ; mycophénolate mofetil (MMF) chez 11 (11 R) ; méthotrexate chez 8 (4 R) ; cyclophosphamide chez 8 (7 R) ; ciclosporine chez 1 (non R). Le MMF permettait une R persistante : en première ligne (2 cas), après échec du RTX (2 cas), du RTX + ≥ 1 IS (4 cas), et du RTX + ≥ 1 IS + ≥ 1 aRTPO (2 cas). Le RTX était administré dans 29 cas (21 R dont 8 justifiant ensuite ≥ 1 TS). Douze patients (15 %) étaient traités par aRTPO (1 par les 2 successivement) : 4/5 R sous romiplostim ; 7/8 R sous eltrombopag. Le belimumab permettait 1 R persistante après échec des IS + RTX + splénectomie. Une splénectomie était réalisée chez 15 malades (R persistante : 7/15) et 42 recevaient des immunoglobulines polyvalentes. La proportion de R aux TS était similaire dans le groupe EHM. Treize sujets présentaient des complications thrombotiques (9 avec APL ; 1 thrombose veineuse sous aRTPO) ; 14 présentaient 26 complications infectieuses (5 graves) ; 4 devaient être admis en réanimation. Parmi les 3 décès répertoriés 1 seul était directement attribuable à la TICS. Malgré les nombreux biais inhérents à sa méthodologie, cette étude souligne la morbidité de la TICS secondaire au LES et en particulier du « groupe EHM » et identifie les traitements souvent rentables : MMF, RTX et aRTPO. [ABSTRACT FROM AUTHOR]

Au cours de la sclérodermie systémique (ScS), l'atteinte digestive est très fréquente et peut concerner les différents étages du tube digestif. La pseudo occlusion intestinale chronique (POIC) représente une atteinte sévère du grêle pouvant empêcher toute alimentation entérale et relevant alors d'une nutrition thérapeutique parentérale (NP). Nous avons décidé de décrire les ScS avec POIC nourries par NP et d'étudier la faisabilité et les risques de cette approche nutritionnelle. Nous avons mené une analyse rétrospective des patients atteints de ScS suivis dans le service de médecine interne et maladies multi-organiques au CHRU de Montpellier, de 1985 à 2019. Le critère d'inclusion était le recours, au-delà de 14 jours, à une NP du fait d'une POIC. Le poids, l'IMC et le score MUST (Malnutrition Universal Screening Tool) ont été recueillis. Une POIC était retrouvée chez six des 120 patients sclérodermiques de notre série (5 %), dont une avec une forme sine scleroderma. Une patiente avait des anticorps anti-scl70, deux des anti-fibrillarine (AFA) associés à des antinucléaires, deux des antinucléaires isolés et une ne présentait pas d'auto-anticorps détectable. Le délai médian de survenue de la POIC après le diagnostic de ScS était de 7 ans. Toutes les patientes avaient une atteinte œsophagienne, 2/6 une atteinte anale et 4/6 souffraient de pullulation microbienne au diagnostic et au cours du suivi. Les autres atteintes étaient les suivantes : pulmonaire interstitielle (n = 3/6), artérielle pulmonaire (n = 2/6), cardiaque (n = 2/6), et musculaire (n = 1/6). Cinq patientes ont reçu un traitement immunosuppresseur et trois des IgIV. Toutes ont reçu des prokinétiques (domperidone, octréotide, erythromycine). Quatre patientes avaient un score MUST de dénutrition sévère ≥ 2 au diagnostic de POIC. Le poids médian au début de la NP était de 49 kg [36–53]. La prise pondérale médiane à 6 mois et 1 an était respectivement de 8,97 et 11,22 % sous NP avec une ascension moyenne de l'albumine de 0,9 et 3,3 grammes respectivement. L'IMC progressait de 8,2 et 7,2 % respectivement à 6 et 12 mois du début de la NP. La durée médiane de NP était de 805 jours [20–2990]. Les accès veineux centraux comprenaient des dispositifs veineux implantables (DVI), posés chez tous nos patients, 2 Picc-line® ainsi qu'un cathéter Broviac®. Toutes étaient suivies en centre expert régional de nutrition. Les complications du traitement étaient : infectieuses (n = 8) et thrombotiques (n = 4) liées au cathéter, ainsi que cardiaques (n = 3) avec une mauvaise tolérance hémodynamique (en lien avec une cardiopathie spécifique de la ScS chez une patiente). Chaque complication donnait lieu à une réhospitalisation. Tous dispositifs confondus, les taux d'infection et de thrombose étaient respectivement de 1,16 et 0,58/1000 jours-cathéters pour 6856 jours d'utilisation. Enfin, trois réhospitalisations faisaient suite à une surcharge cardiaque en lien avec la NP. L'une fut fatale. L'autre décès était lié à une perforation digestive. La POIC concerne environ 5 % des SSc [1]. Du fait de ses conséquences, la NP est parfois la seule option viable et nécessite un centre expert pour la confection des poches et le suivi. La NP assure un gain pondéral substantiel et nos résultats sont concordants avec la littérature. Les complications sont majoritairement hémodynamiques et infectieuses et semblent plus fréquentes dans notre étude que dans la littérature ScS [2]. Par ailleurs, la détection d'AFA semble associée à un pronostic plus sévère, comme décrit dans la littérature [3]. La POIC est un tournant majeur dans l'évolution de la ScS. La NP est d'autant plus justifiée qu'elle permet un gain pondéral substantiel. [ABSTRACT FROM AUTHOR]

Background: Anemia affects up to 25% of emergency department (ED) patients. Restrictive red blood cell (RBC) transfusion strategies are recommended for stable patients, but ED transfusion practices often remain liberal. Benefits of ED transfusion remains unclear., Objective: To evaluate the impact of ED transfusion on death-adjusted in-hospital length of stay (LOS) in stable anemic patients requiring hospitalization., Methods: This single-center retrospective propensity-matched study included patients ≥ 18 years admitted to the ED of Nîmes University Hospital in 2022 with hemoglobin levels between 70 and 90 g.L - 1 . Patients with hemorrhagic shock or requiring emergent hemostatic procedures were excluded. Propensity score matching was conducted on variables including age, comorbidities, hemoglobin levels, and diastolic blood pressure. Primary outcome was adjusted in-hospital LOS. Secondary outcomes included ED LOS and RBC transfusion volumes., Results: Among 564 patients, 118 (21%) were propensity-matched: 59 (50%) ED-transfused, 59 (50%) non-ED-transfused. Adjusted in-hospital LOS 13 [8-32] for ED-transfused patients and 12 [6-24] days for non-ED-transfused patients (median difference = 0; 95%CI: -10-7; p = 0.52). Median difference in ED LOS was 7:13 (95%CI: 1:00-11:25; p < 0.001) between ED transfused and non-ED-transfused patients. Median difference in number of RBC transfused during in hospital stay was 2 (95%CI: 1-3); p < 0.01) between ED transfused and non-ED-transfused patients., Conclusion: In stable anemic patients with 70 to 90 g.L - 1 hemoglobin level, ED transfusion did not reduce adjusted in-hospital LOS but prolonged ED LOS. Identifying patients who may safely defer transfusion could improve ED efficiency and safety., Competing Interests: Declarations. Ethics approval and consent to participate: The local ethics committee of Nimes’ university hospital approved the study (Nîmes University Hospital IRB 23.05.02) and waived the consent in accordance with French law (Law no. 2012 − 300 of 5 March 2012 on research involving the human person). A non-opposition letter was sent to patients or their relatives if patients died during hospitalisation, explaining the aims of the study and the possibility of refusing data collection. The authors did not receive any refusals. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Clinical trial number: not applicable., (© 2025. The Author(s).)

Objectives: To assess the comparative safety of tumor necrosis factor inhibitor (TNFi), non-TNFi, and Janus kinase inhibitor (JAKi) biologic or targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARD) in patients with rheumatoid arthritis (RA) for the risk of major adverse cardiovascular events (MACE) using US administrative claims data., Methods: We performed a cohort study using MerativeTM Marketscan® Research Databases (2012-2021) of individuals aged 18-64 years with RA initiating b/tsDMARD treatment. We used Cox proportional hazard models to estimate hazard ratios (HR) and 95% CI for developing MACE within 2 years of b/tsDMARD initiation, adjusting for potential confounders., Results: We included a total of 34 375 treatment exposures: 71% TNFi, 10% JAKi, 8% abatacept, 5% rituximab, and 5% IL-6i. Most individuals were female (77-84%) with a median (interquartile range) of 50 (42, 56) years. Rituximab had the highest incidence rate of MACE (196/10 000 person-years; 95% CI 126, 291), followed by IL-6i (111/10 000 person-years; 95% CI 57, 193). Multivariable analyses showed non-statistically significantly higher MACE risk with rituximab (HR 1.5; 95% CI 0.9, 2.4) and IL-6i (HR 1.3; 95% CI 0.7, 2.4) exposures but no increased risk with JAKi relative to TNFi use., Conclusion: In this large nationwide study, rituximab and IL-6i users had numerically higher, but not statistically significant, MACE risk. Our data support the safety of b/tsDMARD use for RA treatment. This study was limited by short follow-up time and confounding by indication; further studies that can overcome these limitations are needed., (© The Author(s) 2025. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

It remains unknown whether frailty status confers an increased risk of readmission in patients with rheumatoid arthritis (RA). From the 2018 Nationwide Readmissions Database (NRD), we identified adult patients (age ≥ 18 years) admitted with a diagnosis of RA between January to June 2018. Utilizing validated Hospital Frailty Score, patients' frailty risk score was calculated at the time of index admission and categorized into frail (score ≥ 5) and non-frail (score < 5) groups. Our primary outcomes of interest were (1) 180- day readmission rate (2) inpatient mortality; secondary outcomes included prolonged length of stay, LOS (LOS ≥ 7 days), and costs of hospitalization. Multivariable Cox proportional hazard analysis was performed to evaluate the independent effect of frailty adjusting for confounding variables. 133,187 patients met inclusion criteria, with mean age 67.7 years, of whom 64,131 (48.1%) patients were categorized as frail. The rate of readmission was significantly higher in the frail (56.60%) compared to the non-frail group (30.61%). At index hospitalization, frail patients also had significantly higher inpatient mortality compared to non-frail patients (3.36% vs 0.39%, p < 0.005), longer LOS (26.24% vs 7.82%, p < 0.005). On multivariate analysis frailty was independently associated with a 9% increased risk of readmission (adjusted hazard ratio, 1.09; 95% confidence interval, 1.08 - 1.11). People with RA who are frail have higher rates of readmission than those who are not frail. These findings are crucial in identifying at-risk patients with RA and in discharge planning after hospitalization. Key Points • People with RA who are frail have higher rates of readmission than those who are not frail. • Frail RA patients are also at higher risk of hospitalization-related adverse outcomes, including inpatient mortality and longer hospital stay. • Sepsis is the most common cause for readmission identified in frail patients with RA. • These findings suggest that frailty may be a useful metric in identifying patients with RA at an increased risk of adverse health outcomes., Competing Interests: Declarations. Conflict of interest: No conflicts of interest to disclose., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Importance: The Oral Rheumatoid Arthritis Trial Surveillance demonstrated an increased cancer risk among patients with rheumatoid arthritis (RA) taking tofacitinib compared with those taking tumor necrosis factor inhibitors (TNFis). Although international cohort studies have compared cancer outcomes between TNFis, non-TNFi drugs, and Janus kinase inhibitor (JAKis), their generalizability to US patients with RA is limited., Objective: To assess the comparative safety of TNFis, non-TNFi drugs, and JAKis among US patients with RA (ie, the cancer risk associated with the use of these drugs among these patients)., Design, Setting, and Participants: This retrospective cohort study used US administrative claims data from Merative Marketscan Research Databases from November 1, 2012, to December 31, 2021. Follow-up occurred up to 2 years after initiation of biologic or targeted synthetic disease-modifying antirheumatic drugs (DMARDs). Participants included individuals aged 18 to 64 years with RA, identified using at least 2 RA International Classification of Diseases, Ninth Revision or International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnostic codes on or before the date of TNFi, non-TNFi, or JAKi initiation ("index date"). Statistical analysis took place from June 2022 to September 2024., Exposures: New initiations of TNFis, abatacept, interleukin 6 inhibitors (IL-6is), rituximab, or JAKis. Individuals could contribute person-time to more than 1 treatment exposure if treatment escalation mimicked typical clinical practice but were censored if they switched to a previously trialed medication class., Main Outcomes and Measures: Incident cancer, excluding nonmelanoma skin cancer, after at least 90 days and within 2 years of initiation of biologic or targeted synthetic DMARDs. Outcomes were associated with the most recent drug exposure., Results: Of the 25 305 individuals who initiated treatment and who met the inclusion criteria, most were female (19 869 [79%]), had a median age of 50 years (IQR, 42-56 years), and were from the South US (12 516 [49%]). Of a total 27 661 drug exposures, drug initiations consisted of 20 586 TNFi exposures (74%), 2570 JAKi exposures (9%), 2255 abatacept exposures (8%), 1182 rituximab exposures (4%), and 1068 IL-6i exposures (4%). Multivariable Cox proportional hazards regression analysis showed that rituximab was associated with a higher risk of incident cancer compared with TNFis (hazard ratio [HR], 1.91; 95% CI, 1.17-3.14), followed by abatacept (HR, 1.47; 95% CI, 1.03-2.11), and JAKis (HR, 1.36; 95% CI, 0.94-1.96)., Conclusions and Relevance: In this cohort study of individuals with RA and new biologic or targeted synthetic DMARD exposures, individuals initiating rituximab, abatacept, and JAKis demonstrated higher incidence rates and statistically significantly increased risks of incident cancers compared with those initiating TNFis in the first 2 years after initiation of biologic or targeted synthetic DMARDs. Given the limitations of administrative claims data and confounding by indication, it is likely that these patients may have a higher disease burden, resulting in channeling bias. To better understand these associations, larger studies with longer follow-up time are needed.

Objective: The objective of this study was to evaluate the association between frailty status and risk of readmissions, inpatient death, and cost of admission among patients with systemic lupus erythematosus (SLE)., Methods: We conducted a retrospective cohort study using the National Readmissions Database. Using International Statistical Classification of Diseases, Tenth Revision codes, we identified individuals >18 years of age who had a primary or secondary diagnosis of SLE and were hospitalized between January and June 2018. Using the validated claims-based Hospital Frailty Risk Score, we categorized individuals as frail (score ≥ 5) or nonfrail (score < 5) at the time of index hospitalization. Our primary outcome was readmission rates post discharge from index hospitalization. Secondary outcomes were rates of inpatient mortality and the total cost of hospitalizations. Cox proportional hazard models were used to estimate the association between frailty and risk of readmissions, with adjustment for age, sex, insurance type, household income, and Elixhauser Comorbidity Index score., Results: A total of 39,738 patients with SLE met eligibility criteria. Over a median follow-up of eight months, frail patients with SLE (n = 18,385) had higher Elixhauser Comorbidity Index scores and longer length of stay compared to nonfrail patients with SLE (n = 21,353). Frail patients with SLE had higher readmission rates, a higher proportion of prolonged hospitalizations, and higher costs per hospitalization. Frailty was independently associated with a 10% higher risk of readmission after adjustment for covariates., Conclusion: Among hospitalized adults with SLE, presence of frailty was associated with higher readmission and inpatient mortality rates. Our results highlight that frailty status can help risk stratify patients with SLE at increased risk for readmissions and other adverse health outcomes., (© 2024 The Author(s). ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objectives: Systemic sclerosis (SSc) can cause malnutrition due to frequent gastrointestinal involvement. However, prevalence of malnutrition in SSc is poorly known. The aim of this study was to evaluate the prevalence of malnutrition in SSc and its potential associations with disease features in patients from a tertiary referral center., Methods: All patients meeting American College of Rheumatology/European Alliance of Associations for Rheumatology criteria for SSc followed between January 1, 1985, and January 1, 2019, at the Department of Internal Medicine, Saint Eloi University Hospital, were included. Malnutrition was assessed using the 2020 French recommendations for SSc and the malnutrition universal screening tool score. Severe malnutrition was defined via the French Haute Autorité de Santé (National Health Authority) 2007 criteria., Results: A total of 120 patients were included, with mean age 64 (± 15) y and a female-to-male sex ratio of 5:1. According to 2020 French recommendations, 71 patients (59.2%) were malnourished and 30 (25%) had at least one criterion of severe malnutrition. With the malnutrition universal screening tool score, 41.7%, 20%, and 38.3%, respectively, had low, medium, and high risk of malnutrition. Multivariate analysis revealed the following results: 1) malnutrition was associated with cardiac involvement (P < 0.01); 2) a high malnutrition universal screening tool score was also associated with specific cardiac involvement (P < 0.01); and 3) severe malnutrition was strongly correlated with interincisal distance <35 mm (P = 0.02)., Conclusions: Malnutrition affects more than half of SSc patients and is associated with specific cardiac involvement. Interincisal distance <35 mm could be a red flag for severe malnutrition in SSc., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: While the incidence and type of blood malignancies are well documented amid primary Sjögren's syndrome patients (pSS), data focusing on solid neoplasms are more conflicting. We aimed to describe clinical, pathological, and immunological characteristics of pSS patients with cancers, along with the chronological interplay between the two conditions., Methods: Outcomes concerning both pSS and cancer were retrospectively collected from Montpellier University Hospital (tertiary center) between 2019 and 2020. pSS characteristics were compared to a control group of pSS patients without cancer., Results: A total of 165 patients with pSS were included: 55 patients with cancer (52 female, mean age 58.4 ± 10.4 years at pSS diagnosis; mean follow-up 10.5 ± 10.1 years, 12 patients had multiple cancers) and 110 controls without cancer. Characteristics of pSS patients with cancers were different from controls mostly for lymphoma prognosis factors. Among the 70 cancers, we recorded 55 solid neoplasms (whom 27 breast cancers and 8 lung cancers, and 82% of adenocarcinomas), with no evidence of disease at the end of follow-up in 85% of them. Among the 15 recorded blood malignancies, ten were lymphomas with an excellent prognosis. Regarding chronological interplay between cancer and pSS, most cancers (43%) were diagnosed close (± 5 years) to pSS diagnosis. Breast cancers were diagnosed before or close to pSS diagnosis (mean delay - 1.8 ± 13.0 years), at an early stage, with only two relapses (no cancer-related death), while lung cancers were diagnosed late after., Conclusions: The tight chronological interplay between breast cancer and pSS and the intriguing pathological and immunological pattern of pSS in these patients suggest a hypothesis of immune control of cancer., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: CTLA4 deficiency (CTLA4d) is a disease with multisystem autoimmune features, including neurologic manifestations. We aimed to describe neurologic involvement in these patients., Methods: We performed a cross-sectional observational study using the French Reference Centre for Primary Immunodeficiencies (CEREDIH) registry plus a surveillance in national society networks. Participants with confirmed CTLA4d and neurologic involvement were included. Clinical, laboratory, and radiologic features were collected, as well as treatments. Available MRI was double-reviewed., Results: Among 70 patients with CTLA4d, 13 patients (21%) had neurologic involvement. Neurologic symptoms began at a median age of 18 [15-45] years, mostly occurring after systemic manifestations (median delay: 8.5 [4.5-10.5] years). Main symptoms included headaches, focal deficit (54% each), and seizures (38%). MRI detected at least 1 large contrast-enhancing lesion in 8 patients. Lesions reminiscent of multiple sclerosis lesions were found in 6 patients. Cerebellar (6 patients) and large spinal cord lesions (3 patients) were common. Ten patients were treated with abatacept, of whom 9 (90%) showed good clinical and radiologic response., Discussion: Neurologic involvement is common among patients with CTLA4d. Despite its rarity, and considering the suspected efficacy of abatacept, neurologists should be aware of the characteristics of CTLA4d neurologic involvement., (© 2023 American Academy of Neurology.)

Objective: To identify the key coding genes underlying the biomarkers and pathways associated with giant cell arteritis (GCA), we performed an in situ spatial profiling of molecules involved in the temporal arteries of GCA patients and controls. Furthermore, we performed pharmacogenomic network analysis to identify potential treatment targets., Methods: Using human formalin-fixed paraffin-embedded temporal artery biopsy samples (GCA, n = 9; controls, n = 7), we performed a whole transcriptome analysis using the NanoString GeoMx Digital Spatial Profiler. In total, 59 regions of interest were selected in the intima, media, adventitia, and perivascular adipose tissue (PVAT). Differentially expressed genes (DEGs) (fold-change > 2 or < -2, p-adjusted < 0.01) were compared across each layer to build a spatial and pharmacogenomic network and to explore the pathophysiological mechanisms of GCA., Results: Most of the transcriptome (12,076 genes) was upregulated in GCA arteries, compared to control arteries. Among the screened genes, 282, 227, 40, and 5 DEGs were identified in the intima, media, adventitia, and PVAT, respectively. Genes involved in the immune process and vascular remodeling were upregulated within GCA temporal arteries but differed across the arterial layers. The immune-related functions and vascular remodeling were limited to the intima and media., Conclusion: This study is the first to perform an in situ spatial profiling characterization of the molecules involved in GCA. The pharmacogenomic network analysis identified potential target genes for approved and novel immunotherapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Parreau, Molina, Dumonteil, Goulabchand, Naves, Bois, Akil, Terro, Fauchais, Liozon, Jauberteau, Weyand and Ly.)

Objective: Giant cell arteritis (GCA) has a relapsing-remitting course and is associated with a high burden of comorbidities, leading to repeated hospitalizations. This study was undertaken to investigate the burden, risk factors, causes, and outcomes of hospitalization and readmission in GCA patients in a US national cohort., Methods: Using the 2017 US National Readmission Database, we identified adults ≥50 years of age hospitalized with GCA between January and June 2017, with at least 6 months of follow-up. We estimated the burden of hospitalization including 6-month risk of readmission, total days spent in hospital, and costs, annually. We examined patient-, hospital-, and index hospitalization-related factors for 6-month readmission and total days of hospitalization using binomial logistic regression., Results: Our study included 1,206 patients hospitalized with GCA (70% women, median age 77 years), with 13% of patients experiencing GCA-related ophthalmologic complications at index hospital admission. On follow-up, 3% died, and 34% of patients were readmitted within 6 months, primarily for infections (23%) and cardiovascular diseases (CVDs) (15%). Charlson comorbidity index (CCI) of ≥1, smoking, and obesity were associated with readmission. GCA patients spent a median of 5 days/year in hospital (interquartile range [IQR] 3-11), with those in the top quartile spending 19 days/year in hospital (IQR 14-26)., Conclusion: GCA patients frequently experience unplanned health care utilization, with 1 in 3 patients experiencing readmission within 6 months, and 3% dying within the follow-up period. Infection and CVDs are common causes of readmission and may be related to glucocorticoid exposure. Population health management strategies are required in these vulnerable GCA patients., (© 2022 American College of Rheumatology.)

Introduction: Involvement of subcutaneous tissue in idiopathic inflammatory myopathies (IIM) is poorly known., Methods: We conducted a systematic review of the literature regarding panniculitis and lipodystrophy/lipoatrophy in juvenile and adult IIM via PubMed/Medline, Embase and Scopus databases. Three local observations are included in this review. Epidemiological, clinical, paraclinical and therapeutic data were collected., Results: Panniculitis appears to be more common in adults than in juveniles. It was mainly localised in the upper and lower limbs. Panniculitis improved in most cases with steroids and panniculitis and myositis had a similar course in 83.3% and 72.2% of cases in juveniles and adults, respectively. Lipodystrophy appeared to be more frequent in juveniles and was only observed in dermatomyositis in both juveniles and adults. Lipodystrophy was mainly partial in juveniles and adults. The median time from myositis to the diagnosis of lipodystrophy was 6 years [0-35] and 2.5 years [0-10] in juveniles and adults, respectively. Lipodystrophy was associated with anti-TIF1 gamma auto-antibody positivity, a polycyclic/chronic course of myositis and the occurrence of calcinosis and might be an indicator of poor disease control., Conclusion: Adipose tissue involvement, particularly lipodystrophy, occurs almost exclusively in dermatomyositis. The insidious onset and lack of awareness of the diagnosis may underestimate its prevalence. Larger studies are needed to identify possible risk factors in these patients, to better potential underlying pathophysiological process, in order to discuss potential therapeutic targets., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

We aimed to assess the factors associated with mortality in patients treated with tocilizumab for a SARS-CoV-2 pneumonia due to the delta or omicron variants of concern (VOC) and detect an effect of tocilizumab on mortality. We conducted a prospective cohort study in a tertiary hospital from 1 August 2021 to 31 March 2022 including patients with severe COVID-19, treated with tocilizumab. Factors associated with mortality were assessed in a Cox model; then, the 60-day mortality rates of COVID-19 patients treated with standard of care (SoC) +/- tocilizumab were compared after 1:1 propensity score matching. The mortality rate was 22% (N = 26/118) and was similar between delta and omicron cases ( p = 0.6). The factors independently associated with mortality were age (HR 1.06; 95% CI (1.02-1.11), p = 0.002), Charlson index (HR 1.33; 95% CI (1.11-1.6), p = 0.002), WHO-CPS (HR 2.56; 95% CI (1.07-6.22) p = 0.03), and tocilizumab infusion within the first 48 h following hospital admission (HR 0.37, 95% CI (0.14-0.97), p = 0.04). No significant differences in mortality between the tocilizumab plus SoC and SoC alone groups ( p = 0.5) were highlighted. However, the patients treated with tocilizumab within the 48 h following hospital admission had better survival ( p = 0.04). In conclusion, our results suggested a protective effect on mortality of the early administration of tocilizumab in patients with severe COVID-19 regardless of the VOC involved.

Background: Primary Sjögren's syndrome (pSS) is an autoimmune disease with increased risk of infections. Here, we assessed whether pSS patients were at higher risk of hospitalization for community and opportunistic infections., Methods: We selected newly hospitalized pSS patients between 2011 and 2018, through a nationwide population-based retrospective study using the French Health insurance database. We compared the incidence of hospitalization for several types of infections (according to International Classification for Disease codes, ICD-10) between pSS patients and an age- and sex-matched (1:10) hospitalized control group. We calculated adjusted Hazard Ratios (aHR, 95% CI) adjusted on socio-economic status, past cardiovascular or lung diseases and blood malignancies factors., Results: We compared 25 661 pSS patients with 252 543 matched patients. The incidence of hospitalizations for a first community infection was increased in pSS patients [aHR of 1.29 (1.22-1.31), p  < .001]. The incidence of hospitalization for bronchopulmonary infections was increased in pSS patients [aHR of 1.50 (1.34-1.69), p  < .001, for pneumonia]. Hospitalizations for pyelonephritis and intestinal infections were increased [aHR of 1.55 (1.29-1.87), p  < .001 and 1.18 (1.08-1.29), p  < .001, respectively]. Among opportunistic infections, only zoster, and mycobacteria infections (tuberculosis and non-tuberculous) were at increased risk of hospitalization [aHR of 3.32 (1.78-6.18), p  < .001; 4.35 (1.41-13.5), p  = .011 and 2.54 (1.27-5.06), p  = .008, respectively]., Conclusions: pSS patients are at higher risk of hospitalization for infections. The increased risk of hospitalization for mycobacterial infections illustrates the potential bilateral relationship between the two conditions. Vaccination against respiratory pathogens and herpes zoster virus may help prevent some hospitalizations in pSS patients.KEY MESSAGESPrimary Sjögren's syndrome (pSS) increases hospitalization risk for community infections: bronchopulmonary, skin, dental, ear-nose-throat, intestinal infections and pyelonephritis.Hospitalizations for zoster and mycobacterial infections are also increased in this population.Dedicated preventive measures and vaccination campaigns could decrease the burden of infections in pSS patients.

Objectives: To describe the characteristics, treatment and outcome of patients with immune thrombocytopenia with clinical significance (ITPCS) associated with SLE., Methods: This retrospective multicentre study included SLE patients who experienced ≥1 ITPCS (defined as ITP with attributable bleeding disorders and/or a platelet count <30×109/l). Other causes of secondary thrombocytopenia were excluded. Major bleeding event (MBG) was defined as Khellaf score >8 and/or WHO score >2., Results: A total of 90 patients were included, the median (range) follow-up duration was 80 (6-446) months. ITP was diagnosed before SLE in 25 patients. They presented a high rate of autoimmune haemolytic anaemia (15%), antiphospholipid antibody (62%) and antiphospholipid syndrome (19%). The 25 (28%) patients who experienced MBG had significantly more bleedings at ITP diagnosis and higher bleeding scores, and serositis and thrombosis during follow-up. They required significantly more treatment lines, transfusions and hospitalizations. The 11 (12%) patients who experienced no bleeding event presented a significantly more restricted SLE phenotype (cutaneous and/or articular). Patients received a mean (range) of 4.2 (1-11) treatment lines. Corticosteroids and HCQ allowed ITPCS overall response in one-third of patients. The median relapse-free survival of rituximab (n = 34), AZA (n = 19), MMF (n = 8), thrombopoietin-receptor agonists (n = 16) and splenectomy (n = 19) were 53, 31.5, 61, 24.5 and 78 months, respectively. Four patients experienced thrombotic events after splenectomy and one occurred under thrombopoietin-receptor agonist treatment., Conclusion: SLE-ITCS patients displayed a high rate of haematological abnormalities and MBG patients exhibited higher morbidity. Management of thrombocytopenia was highly heterogeneous and many options seem viable., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: We aimed to investigate whether anakinra, an interleukin-1receptor inhibitor, could improve outcome in moderate COVID-19 patients., Methods: In this controlled, open-label trial, we enrolled adults with COVID-19 requiring oxygen. We randomly assigned patients to receive intravenous anakinra plus optimized standard of care (oSOC) vs. oSOC alone. The primary outcome was treatment success at day 14 defined as patient alive and not requiring mechanical ventilation or extracorporeal membrane oxygenation., Results: Between 27th April and 6th October 2020, we enrolled 71 patients (240 patients planned to been enrolled): 37 were assigned to the anakinra group and 34 to oSOC group. The study ended prematurely by recommendation of the data and safety monitoring board due to safety concerns. On day 14, the proportion of treatment success was significantly lower in the anakinra group 70% (n = 26) vs. 91% (n = 31) in the oSOC group: risk difference-21 percentage points (95% CI, -39 to -2), odds ratio 0.23 (95% CI, 0.06 to 0.91), p = 0.027. After a 28-day follow-up, 9 patients in the anakinra group and 3 in the oSOC group had died. Overall survival at day 28 was 75% (95% CI, 62% to 91%) in the anakinra group versus 91% (95% CI, 82% to 100%) (p = 0.06) in the oSOC group. Serious adverse events occurred in 19 (51%) patients in the anakinra group and 18 (53%) in the oSOC group (p = 0·89)., Conclusion: This trial did not show efficacy of anakinra in patients with COVID-19. Furthermore, contrary to our hypothesis, we found that anakinra was inferior to oSOC in patients with moderate COVID-19 pneumonia., Competing Interests: The authors have declared that no competing interests exist.

Primary Sjögren's syndrome (pSS) is an autoimmune disease with frequent neurological involvement. Memory complaints are common, but their precise patterns remain unclear. We wanted to characterize patterns of neurocognitive profiles in pSS patients with cognitive complaints. Only pSS patients with memory complaints were included, prospectively. Cognitive profiles were compiled through a comprehensive cognitive evaluation by neuropsychologists. Evaluations of anxiety, depression, fatigue, sleep disorders and quality of life were performed for testing their interactions with cognitive profiles. All 32 pSS patients showed at least borderline cognitive impairment, and 17 (53%) exhibited a pathological cognitive profile: a hippocampal profile (37%), a dysexecutive profile (22%), and an instrumental profile (16%) (possible overlap). Regarding the secondary objectives: 37% of patients were depressed, and 48% exhibited a mild-to-severe anxiety trait. Sleep disorders were frequent (excessive daytime sleepiness (55%), high risk for sleep apnea (45%), and insomnia (77%)). Cognitive impairments could not be explained alone by anxiety, depression or sleep disorders. Fatigue level was strongly associated with sleep disorders. Our study highlights that cognitive complaints in pSS patients are supported by measurable cognitive impairments, apart from frequently associated disorders such as depression, anxiety or sleep troubles. Sleep disorders should be screened., (© 2022. The Author(s).)

Objectives: Sjögren's syndrome (SS) and ANCA-associated vasculitis (AAV) have distinct clinical presentation and evolution, with paucity of reports on overlap syndrome. We aimed to better characterize this entity., Methods: We report four additional cases from the Montpellier university hospital. We also performed a systematic literature review, according to PRISMA guidelines, in Medline, Embase, Web of science, Cochrane Library, and grey literature. Demographic, clinical, and paraclinical data on SS and AAV were analysed., Results: A total of 3133 articles was identified in databases, with 2695 articles screened for eligibility. After exclusion, we had 30 articles on 40 patients to analyse, in addition to 4 patients from our local recruitment (44 patients overall). Patients were female in 81.8%, with median age at AAV onset of 63.5 years. All patients but one presented with SS before, or concomitantly to the diagnosis of AAV, with a median delay of 12 months between both diagnoses. AAV predominantly had renal involvement (35/44 patients, 79.5%), anti-MPO antibodies being the most frequent (35 patients), even in patients presenting with granulomatosis with polyangiitis. We observed significantly more Raynaud phenomenon and associated auto-immune diseases in the group of non-granulomatous AAV (10 patients versus 1, p = 0.015 and 8 patients versus 0, p = 0.013, respectively)., Conclusions: This is the largest descriptive study on the association between SS and AAV, providing information on this challenging diagnosis and interplay between these two diseases. Particular attention should be paid in the first months after diagnosis, given the specific complications and outcomes of each disease., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Inflammation of unknown origin (IUO) is a challenging situation in internal medicine., Objectives: To describe the final diagnoses in IUO and assess the helpfulness of 18 F-fluorodesoxyglucose positron emission tomography with computerized tomography ( 18 F-FDG-PET/CT) in the diagnosis strategy., Results: A total of 317 IUO patients with 18 F-FDG-PET/CT were enrolled. A diagnosis was reached in 228 patients: noninfectious inflammatory diseases (NIID) (37.5%), infectious diseases (18.6%), malignancies (7.9%), and non-systemic-inflammatory miscellaneous diseases (7.9%). The two leading causes of NIID were polymyalgia rheumatica and giant cell arteritis. 18 F-FDG-PET/CT results were classified as true positive in 49.8% of patients and contributory in 75.1% of overall IUO patients (after the complete investigation set and a prolonged follow-up). In multivariate analysis, only C-reactive protein minimum level (≥50 mg/L) was associated with the contributory status of 18 F-FDG-PET/CT., Conclusion: Within the wide spectrum of IUO underlying diseases, 18 F-FDG-PET/CT is helpful to make a diagnosis and to eliminate inflammatory diseases. Obese patients constitute a specific group needing further studies., (© 2022 The Association for the Publication of the Journal of Internal Medicine.)

Objectives: Giant cell arteritis (GCA) is associated with severe outcomes such as infections and cardiovascular diseases. We describe here the impact of GCA patients’ characteristics and treatment exposure on the occurrence of severe outcomes. Methods: Data were collected retrospectively from real-world GCA patients with a minimum of six-months follow-up. We recorded severe outcomes and treatment exposure. In the survival analysis, we studied the predictive factors of severe outcomes occurrence, including treatment exposure (major glucocorticoids (GCs) exposure (>10 g of the cumulative dose) and tocilizumab (TCZ) exposure), as time-dependent covariates. Results: Among the 77 included patients, 26% were overweight (BMI ≥ 25 kg/m2). The mean cumulative dose of GCs was 7977 ± 4585 mg, 18 patients (23%) had a major GCs exposure, and 40 (52%) received TCZ. Over the 48-month mean follow-up period, 114 severe outcomes occurred in 77% of the patients: infections—29%, cardiovascular diseases—18%, hypertension—15%, fractural osteoporosis—8%, and deaths—6%. Baseline diabetes and overweight were predictive factors of severe outcomes onset (HR, 2.41 [1.05−5.55], p = 0.039; HR, 2.08 [1.14−3.81], p = 0.018, respectively) independently of age, sex, hypertension, and treatment exposure. Conclusion: Diabetic and overweight GCA patients constitute an at-risk group requiring tailored treatment, including vaccination. The effect of TCZ exposure on the reduction of severe outcomes was not proved here.

Primary Sjögren’s syndrome (pSS) can be associated with neurological and cognitive involvement, negatively affecting patients’ quality of life. The aim of this study was to assess whether pSS patients are at higher risk of hospitalization for neurological diseases. Through a nationwide retrospective study using the French Health insurance database (based on International Classification for Disease codes, ICD-10), we selected patients hospitalized with new-onset pSS between 2011 and 2018. We compared the incidence of hospitalization for dementia, multiple sclerosis (MS), encephalitis, and peripheral neuropathy with an age- and sex-matched (1:10) hospitalized control group. Adjusted Hazard Ratios (aHR) considered confounding factors, particularly socio-economic status and cardiovascular diseases. We analyzed 25,661 patients hospitalized for pSS, compared with 252,543 matched patients. The incidence of hospitalization for dementia was significantly higher in pSS patients (aHR = 1.27 (1.04−1.55); p = 0.018), as well as the incidence of hospitalization for MS, encephalitis, and inflammatory polyneuropathies (aHR = 3.66 (2.35−5.68), p < 0.001; aHR = 2.66 (1.22−5.80), p = 0.014; and aHR = 23.2 (12.2−44.5), p < 0.001, respectively). According to ICD-10 codes, pSS patients exhibited a higher incidence of hospitalization for dementia, encephalitis, MS, and peripheral neuropathies than controls. Physicians must be aware of these neurological risks to choose the most appropriate diagnostic work-up.

The relationship between cancer and primary Sjögren's syndrome (pSS) is uncertain. While the increased risk of hematological malignancies is well-known, data on the comparative incidence of solid neoplasms is conflicting. This study aimed to explore the associations between cancer and pSS. This nationwide population-based retrospective study from the French health insurance database (PMSI) evaluated patients hospitalized with new-onset pSS from 2011 to 2018 against age- and sex-matched hospitalized controls (1:10). The incidence of hematological malignancies and solid neoplasms was compared between the two groups. Mortality and multiple cancer incidence were also evaluated. Adjusted Hazard Ratios (aHR) calculations included confounding factors, such as low socioeconomic status. Among 25,661 hospitalized patients with pSS versus 252,543 matched patients (median follow-up of 3.96 years), we observed a higher incidence rate of lymphomas (aHR, 1.97 [95% CI, 1.59-2.43]), Waldenström macroglobulinemia (aHR, 10.8 [6.5-18.0]), and leukemia (aHR, 1.61 [1.1-2.4]). Thyroid cancer incidence was higher (aHR, 1.7 [1.1-2.8]), whereas bladder and breast cancer incidences were lower (aHR, 0.58 [0.37-0.89] and 0.60 [0.49-0.74], respectively). pSS patients with breast cancer exhibited a lower mortality rate. A limitation was that the database only encompasses hospitalized patients, and immunological and histological details are not listed. We confirmed the increased risk of hematological malignancies and thyroid cancers among patients with pSS. The lower risk of breast cancer suggests a role of hormonal factors and raises questions of the concept of immune surveillance within breast tissue. Epidemiological and translational studies are required to elucidate the relationships between pSS and cancer., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Primary Sjögren's syndrome (pSS) is an autoimmune disease, associated with a high risk of lymphoma. Mounting evidence suggests that cardiovascular morbidity and mortality are higher in patients with pSS, although data are heterogeneous. The aim of this study was to assess whether pSS patients are at higher risk of hospitalisation for cardiovascular events (CVEs), venous thromboembolic events (VTEs), pulmonary hypertension (PH), and sleep apnoea syndrome (SAS). Through a nationwide population-based retrospective study using the French health insurance database, we selected new-onset pSS in-patients hospitalised between 2011 and 2018. We compared the incidence of CVEs (ischemic heart diseases (IHDs), strokes, and heart failure), SAS, VTEs, and PH with an age- and sex-matched (1:10) hospitalised control group. The calculations of adjusted hazard ratios (aHR) included available confounding factors. We studied 25,661 patients hospitalised for pSS compared with 252,543 matched patients. The incidence of hospitalisation for IHD, SAS, and PH was significantly higher in pSS patients (aHR: 1.20 (1.06-1.34); p = 0.003, aHR: 1.97 (1.70-2.28); p < 0.001, and aHR: 3.32 (2.10-5.25); p < 0.001, respectively), whereas the incidence of stroke, heart failure, and VTE was the same between groups. Further prospective studies are needed to confirm these results and to explore the pathophysiological mechanisms involved.

Context: Primary Sjögren's syndrome (pSS) is a complex heterogeneous autoimmune disease (AID) which can mimic rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). Our exploratory study investigated serum biomarkers that may discriminate pSS from RA and SLE., Methods: Serum concentrations of 63 biomarkers involved in immune cell trafficking, inflammatory response, cellular movement, and cell-to-cell signaling were measured in AID patients, included prospectively into the study at the Montpellier University Hospital. A multivariate analysis by multiple logistic regression was performed, and discriminative power assessed using logistic regression adjusted on significant demographic factors., Results: Among the 95 patients enrolled, 42 suffered from pSS, 28 from RA, and 25 from SLE. Statistical analysis showed that concentrations of BDNF (OR = 0.493 with 95% CI [0.273-0.891]; p = 0.0193) and I-TAC/CXCL11 (OR = 1.344 with 95% CI [1.027-1.76]; p = 0.0314) can significantly discriminate pSS from RA. Similarly, greater concentrations of sCD163 (OR = 0.803 with 95% CI [0.649-0.994]; p = 0.0436), Fractalkine/CX3CL1 (OR = 0.534 with 95% CI [0.287-0. 991]; p = 0.0466), MCP-1/CCL2 (OR = 0.839 with 95% CI [0.732-0.962]; p = 0.0121), and TNFa (OR = 0.479 with 95% CI [0.247-0.928]; p = 0.0292) were associated with SLE diagnosis compared to pSS. In addition, the combination of low concentrations of BDNF and Fractalkine/CX3CL1 was highly specific for pSS (specificity 96.2%; positive predictive value 80%) compared to RA and SLE, as well as the combination of high concentrations of I-TAC/CXCL11 and low concentrations of sCD163 (specificity 98.1%; positive predictive value 75%)., Conclusion: Our study highlights biomarkers potentially involved in pSS, RA, and SLE pathophysiology that could be useful for developing a pSS-specific diagnostic tool., Competing Interests: PGa was employed by company BioRad. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Padern, Duflos, Ferreira, Assou, Guilpain, Maria, Goulabchand, Galea, Jurtela, Jorgensen and Pers.)

We highlight in this short article the side-effects of COVID-19 pandemic on the management of non-COVID patients, with potential detrimental and irreversible complications. We thus propose adjusted strategies to deal with both COVID and non-COVID patients., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To describe the clinical and radiologic neurologic characteristics of patients with cytotoxic T-lymphocyte antigen-4 ( CTLA4 ) haploinsufficiency., Methods: Three patients from 2 families had neurologic manifestations in the context of CTLA4 haploinsufficiency. Their clinical and MRI findings are presented., Results: A 16-year-old boy with a previous diagnosis of combined immunodeficiency presented with severe recurrent episodes of headaches, motor deficit, and seizures associated with waxing and waning gadolinium-enhancing FLAIR cortical/juxtacortical hyperintensities. His sister, who also had combined immunodeficiency, had a brain MRI when she was aged 13 years due to recent headaches and transient right hemianopsia. It revealed a gadolinium-enhancing left occipital white matter hyperintensity. Another 49-year-old woman had progressive visual loss and cerebellar ataxia in the context of recurrent pulmonary infections. All 3 patients were found to have inherited CTLA4 haploinsufficiency. Patient 1's general condition and neurologic manifestations were completely controlled with abatacept (CTLA4-Ig)., Conclusions: These cases suggest that in addition to the variable clinical penetrance and wide spectrum of CTLA4 haploinsufficiency, its neurologic spectrum is broad, ranging from recurrent tumefactive lesions to progressive deficits including cerebellar ataxia and optic atrophy with leukoencephalopathy. These phenotypes must be recognized, and should lead to a complete immunologic workup, because potentially effective targeted immunotherapy exists., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Mastitis frequently affects women of childbearing age. Of all the pathological breast conditions requiring specific management, autoimmune mastitis is in the third position after infection and breast cancer. The aim of this literature review was to make a comprehensive description of autoimmune diseases targeting the mammary gland. Four main histological patterns of autoimmune mastitis are described: (i) lymphocytic infiltrates; (ii) ductal ectasia; (iii) granulomatous mastitis; and (iv) vasculitis. Our literature search found that all types of autoimmune disease may target the mammary gland: organ-specific diseases (diabetes, thyroiditis); connective tissue diseases (such as systemic erythematosus lupus or Sjögren's syndrome); vasculitides (granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, giant cell arteritis, polyarteritis nodosa, Behçet's disease); granulomatous diseases (sarcoidosis, Crohn's disease); and IgG4-related disease. Cases of breast-specific autoimmune diseases have also been reported, including idiopathic granulomatous mastitis. These breast-limited inflammatory diseases are sometimes the first symptom of a systemic autoimmune disease. Although autoimmune mastitis is rare, it is probably underdiagnosed or misdiagnosed. Early diagnosis may allow us to detect systemic diseases at an earlier stage, which could help to initiate a prompt, appropriate therapeutic strategy. In case of suspected autoimmune mastitis, we hereby propose a diagnostic pathway and discuss the potential pathophysiological pathways leading to autoimmune breast damage.

Cancer among patients with systemic sclerosis (SSc) would appear to be more prevalent than in the general population. Pathophysiological hypotheses are multiple, involving intertwined factors such as immune system antitumoral response, oxygen species dysregulation, and immunosuppressive treatments. We aimed to identify SSc patients with cancer monitored at our center, describing their clinical and immunological characteristics, such as cancer-specific outcomes. We focused in particular on the temporal relationships between cancer onset and SSc diagnosis. A retrospective study was conducted on SSc patients from Montpellier University Hospital from 2003 to 2018. Clinical characteristics and outcomes of each SSc patient with cancer were recorded. Fifty-five patients with SSc and at least one cancer was included (median age 56 years (47-66)), with a median follow-up time of 11 years (4-15). Sixty-four metachronous malignancies were identified (12 patients had two cancers). Among them, early-onset cancer occurrences (±5 years from SSc diagnosis) included 23 cancers (39% breast cancers, 13% lung cancers, and 13% gastro-intestinal tract cancers). Twenty-two cancers occurred 10 years (±5 years) after SSc diagnosis (14% breast cancers, 23% gastrointestinal (GI) tract cancers, and 18% lung cancers). Patients without any of the two autoantibodies (anti-centromere (ACA) and anti-topoisomerase (ATA-scl70) antibodies) were more prevalent in the early-onset cancer subgroup (14 vs. 6, p = 0.02). This study brought to light two peaks of cancer occurrence in SSc patients. Early-onset cancers were associated with SSc with a specific immunological signature. Late-onset cancers might be the consequence of a subtle interplay between repeated target organ inflammation, immunosuppressant use, mesenchymal cell dysfunction and subsequent genetic alterations.