Search

Pulmonary hyalinizing granuloma (PHG) is a rare disease characterized by single or multiple benign lung nodules mimicking lung neoplasma. Histologic analysis reveals homogenous hyaline lamellae, usually surrounded by collection of plasma cells, lymphocytes and histiocytes in a perivascular distribution. The clinical and radiological findings have been described in small series, but the long-term outcomes have rarely been reported. The objectives were to describe the clinical, radiological and outcomes of PHG in new cases and through a literature review. Patients with PHG were found by a multicenter search among French departments of internal medicine, pulmonology and anatomo-pathology. Review of the literature was made through the National Library of Medicine's MEDLINE database using keywords 'hyalinizing granuloma.' Five news cases and 135 cases of the literature were found. There were 82 men and 57 women, mean age at the diagnosis 44.6 years (15-83). Patients were frequently asymptomatic ( n = 39, 27.4 %). The nodule was unique in 37 cases (28.9 %) and multiple in 91 cases (71.1 %). 18FDG PET scan revealed hypermetabolism of the nodule in 9/15 cases (60 %). A systemic disease was associated in 65 cases (mainly mediastinal and retroperitoneal fibrosis, autoimmune, tumoral or infectious disease or thromboembolism). The outcomes were evaluated in 73 patients when follow-up was available: 14 patients had a surgical resection of the nodule. Forty-five patients did not receive any immunosuppressive drug. Among these patients, 2 improved, 29 were stable and 14 worsened. Corticosteroids were used as a monotherapy in 19 patients and led to radiological improvement in 8 cases, stabilization in 8 cases and worsening in 3 cases. Five patients were treated with corticosteroids and at least one immunosuppressive drug and 4 patients improved. PHG is a rare benign disease, mimicking lung neoplasma, frequently associated with systemic diseases. [ABSTRACT FROM AUTHOR]

Background: Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis with possible cutaneous-specific involvement.Objectives: We sought to describe the clinical, pathological, and molecular features of the cutaneous manifestations of 40 patients with ECD identified from a cohort of 123 patients.Methods: Confirmed cases of patients with ECD were included in a single-center retrospective observational study. Clinical and pathological cutaneous features were analyzed and BRAF(V600E) mutation was determined.Results: The most frequent ECD cutaneous manifestations were xanthelasma-like lesions (XLL), which occurred in 31 (25%) patients. Other ECD cutaneous lesions were patches or papulonodular lesions. Mixed form of ECD and cutaneous Langerhans cell histiocytosis presented with crusty papules of the folds in some patients. Compared with classic xanthelasma palpebrarum, ECD XLL pathology more frequently involved the reticular dermis, displayed more multinucleated or Touton cells, and showed less extensive fibrosis. BRAF(V600E) mutation was more frequently detected in patients with cutaneous involvement than in those without (76% vs 52%; P = .005) and constantly found in 10 XLL.Limitations: Some clinical data were not available because of the retrospective design of the study.Conclusions: XLL are the most frequent cutaneous ECD manifestations and might be targeted both for pathology and determination of BRAF mutational status. [ABSTRACT FROM AUTHOR]

Objective Intravenous immunoglobulin (IVIG) represents a therapeutic alternative in antineutrophil cytoplasmic antibody-associated vasculitides (AAV), but its efficacy has been evaluated in only 2 small prospective trials. The aim of this study was to evaluate the efficacy and safety of IVIG in patients with AAV. Methods We conducted a nationwide retrospective study of patients who received IVIG as immunomodulatory therapy for AAV. Results A total of 92 patients (mean age 51 years) presenting with either granulomatosis with polyangiitis (Wegener's) (68%), eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (22%), or microscopic polyangiitis (10%) received at least 1 course of IVIG. Antineutrophil cytoplasmic antibodies were present in 72% during the flare that required IVIG, as determined by immunofluorescence assay. IVIG was initiated because of relapsing disease in 83% of cases. IVIG was given for a median of 6 months (range 1-156 months) and in combination with corticosteroids in 21% of the patients or with other immunosuppressive agents in 77%. Efficacy of IVIG was assessed in the entire population and in a subset of 34 patients with unmodified background therapy. Remission rates at 6 months were 56% in the entire population and 58% in the unmodified background therapy group. Refractory disease and treatment failure at 6 months were observed in 7% and 18% in the whole population and 3% and 21% in the unmodified background therapy group, respectively. Adverse events (AEs) occurred in 33%, including serious AEs in 12% and AEs leading to discontinuation of IVIG in 7%. Conclusion This large study shows the clinical benefit of IVIG as adjunctive therapy, with an acceptable tolerance profile, and thus supports its use in AAV patients with refractory or relapsing disease. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown aetiology that can be debilitating and life threatening. As new insights are gained into the underlying pathology of SLE, there have been an unprecedented number of new agents under development to treat the disease via a diverse range of targets. One such class of emerging agents target interferon (IFN) signalling. In this article, we review the preclinical evidence that the inhibition of the secretion and downstream effectors of both IFN-α and IFN-γ may be effective for the treatment of SLE. The primary agents that are currently in clinical development to treat SLE via the targeting of interferon pathways are monoclonal neutralising antibodies (Mab) that bind to and neutralise IFN-γ (AMG 811), IFN-α (sifalimumab, rontalizumab and AGS-009) or its receptor (anifrolumab), and IFN-α kinoid, which is a drug composed of inactivated IFN-α molecules coupled to the keyhole limpet haemocyanin protein. Phase I and II trials have demonstrated acceptable short-term safety with no increase in severe viral infections or reactivation, favourable pharmacokinetic profiles and an inhibition of IFN-associated gene overexpression; however, the impact of these drugs on disease activity must still be assessed in phase III clinical trials. This review concludes with a summary of the challenges that are inherent to this approach to managing SLE. [ABSTRACT FROM AUTHOR]

Objectives Excessive and inappropriate production of pro-inflammatory cytokines plays a key role in Still's disease. Janus kinase inhibitor (JAKi) agents mainly block pro-inflammatory cytokine pathways, notably IL-6 and IFN. The objective was to assess the efficacy and safety of JAKi agents in difficult-to-treat systemic JIA or adult-onset Still's disease (AOSD). Methods This retrospective study was based on a national survey conducted in the departments of rheumatology, paediatric rheumatology and internal medicine of French hospitals regarding systemic JIA and AOSD patients who received JAKi agents. The data were collected with a standardized questionnaire and analysed at different times (treatment initiation, months 1, 3 and 6 and the end of follow-up). Results Nine patients (seven adults) were included. All patients showed inadequate response to CS or conventional synthetic or biologic DMARDs. Baricitinib was used in five patients, ruxolitinib in two, tofacitinib in two and upadacitinib in one. A JAKi was used combined with CS in all but two patients. A JAKi was associated with anakinra and CS in one patient, and with MTX, anakinra and CS in another. The median (range) follow-up was 16 (1–33) months. Two cases out of nine showed complete remission, 3/9 partial response and 4/9 treatment failure. At the last visit, CS could be decreased but not stopped. Tolerance of the JAKi was acceptable (no severe adverse events). Conclusion JAKi agents may be a therapeutic option for some patients with difficult-to-treat Still's disease, especially those with partial response to medium- or high-dose CS or biologics. [ABSTRACT FROM AUTHOR]

(1) Background: The Antiphospholipid Syndrome (APS) is a systemic autoimmune disorder characterized by arterial and/or venous thrombosis, pregnancy morbidity and raised titers of antiphospholipid antibodies. Cerebral vein thrombosis (CVT) is a rare form of cerebrovascular accident and an uncommon APS manifestation; the information in the literature about this feature consists of case reports and small case series. Our purpose is to describe the particular characteristics of CVT when occurs as part of the APS and compare our series with the patients published in the literature. (2) Methods: We conducted a retrospective observational study collecting data from medical records in three referral centers for APS and CVT, and a systematic review of the literature for CVT cases in APS patients. (3) Results: Twenty-seven APS patients with CVT were identified in our medical records, the majority of them diagnosed as primary APS and with the CVT being the first manifestation of the disease; additional risk factors for thrombosis were identified. The review of the literature yielded 86 cases, with similar characteristics as those of our retrospective series. (4) Conclusions: To our knowledge, our study is the largest CVT series in APS patients published to date, providing a unique point of view in this rare thrombotic manifestation. [ABSTRACT FROM AUTHOR]

À l'occasion des états généraux de la médecine interne, le Collège National des Enseignants de Médecine Interne (CEMI) a mené une enquête sur l'activité d'enseignement, auprès de l'ensemble des hospitalo-universitaires (HU) de médecine interne français. L'enquête a été réalisée en septembre 2023 en adressant un courriel aux 101 professeurs des universités–praticiens hospitaliers (PU–PH) et 18 maîtres de conférence des universités–praticiens hospitaliers (MCU–PH) de médecine interne de la sous-section 53-01 du conseil national des universités (CNU), ainsi qu'aux 11 internistes HU émargeant en immunologie (sous-section 47-01) ou en thérapeutique (sous-section 48-04). Soixante-treize HU (56,1 %) ont répondu à l'enquête, dont 65 PU–PH, 7 MCU–PH et 1 praticien hospitalo-universitaire (PHU). Les HU de médecine interne participent à l'enseignement facultaire : 80 % sont responsables d'enseignement, 30 % sont responsables d'année ou de cycle ou animent des commissions et 40 % ont eu ou ont un mandat d'élu à la faculté ou à l'université. Les HU de médecine interne sont investis dans l'enseignement de la sémiologie médicale au cours du premier cycle des études de médecine, mais aussi dans les formations en maïeutique, sciences pharmaceutiques, odontologie et les formations paramédicales. Ils sont très investis dans la mise en place de la réforme du second cycle et 80 % interviennent dans la préparation des Examens Cliniques Objectifs Structurés (ECOS), essentiellement comme examinateurs (90 %). Ils participent également aux enseignements utilisant la simulation (60 %), à l'enseignement aux infirmiers de pratique avancée (IPA) (25 %), à la rédaction des ouvrages du CEMI (75 %). Huit (12 %) HU de médecine interne co-animent des formations avec des patients et 26 (38 %) participent à des enseignements en master à la faculté des sciences. Enfin, 94 % sont affiliés à une unité de recherche et 48 % encadrent des étudiants en thèse d'université. Les HU de médecine interne ont un fort engagement pédagogique, en particulier dans la sémiologie et dans la réforme du second cycle des études médicales avec les ECOS et la simulation. On the occasion of the General stage meeting of Internal Medicine, the National College of Internal Medicine Teachers (CEMI) conducted a survey on teaching activity among all French university hospital (HU) internal medicine specialists. The survey was carried out in September 2023 by sending an email to 101 hospital practitioners university professors (PU–PH) and 18 hospital practitioners assistant professors (MCU–PH) of internal medicine in subsection 53-01 of the National council of universities (CNU), as well as to the 11 HU internists working in immunology (subsection 47-01) or therapeutics (subsection 48-04). Seventy-three HUs (56.1%) responded to the survey, including 65 PU–PH, 7 MCU–PH and 1 university hospital practitioner (PHU). Internal medicine HUs participate in faculty teaching: 80% are responsible for teaching, 30% are responsible for the year or cycle or lead committees and 40% have had or have an elected mandate at the faculty or at university. Internal medicine HU are involved in the teaching of semiology during the first cycle of medical studies, but also in pharmaceutical sciences, dentistry, midwifery and in paramedical training. They are very invested in the implementation of the second cycle reform and 80% are involved in the preparation of Objective Structured Clinical Examinations (ECOS), mainly as examiners (90%). They also participate in teaching using simulation (60%), teaching advanced practice nurses (IPA) (25%), and writing CEMI books (75%). For ECOS, 90% participate as examiners, 60% participate in teaching using simulation, 25% are involved in teaching advanced practice nurses (IPA), 75% participated in the writing of CEMI works. Eight (12%) internal medicine HUs co-facilitate training with patients and 26 (38%) participate in master's courses at the Faculty of Sciences. Finally, 94% are affiliated with a research unit and 48% supervise university theses students. Internal medicine universities teachers have a strong educational commitment, particularly in semiology and in the reform of the second cycle of medical studies with ECOS and simulation. [ABSTRACT FROM AUTHOR]

Summary The immunosuppressive treatment of immune‐mediated thrombotic thrombocytopenic purpura (iTTP) in patients with intolerance or refractoriness to the B‐cell depleting monoclonal antibody rituximab remains debated. Daratumumab, a plasma cell‐directed monoclonal antibody targeting CD38, represents a therapeutic option, but data are scarce. The French Thrombotic Microangiopathies Reference Center conducted a nationwide survey on iTTP patients treated with daratumumab. Nine episodes from seven patients were identified. Treatment was administered for A Disintegrin And Metalloproteinase with ThromboSpondin‐1 motifs, 13th member (ADAMTS13) relapses while patients were otherwise in clinical response (N = 8), or during the acute phase of the disease following rituximab intolerance (N = 1). Patients have received a median of three previous therapeutic lines. ADAMTS13 activity improved in eight cases following daratumumab administration, including three cases where ADAMTS13 normalized. ADAMTS13 relapses occurred in three patients; in two cases, retreatment with daratumumab was successful. Median ADAMTS13 relapse‐free survival was not reached; 12‐month ADAMTS13 relapse‐free survival was 56%. Daratumumab‐related adverse events occurred in five cases and were non‐severe infusion‐related reactions in all cases. These results suggest that daratumumab may be an effective treatment option for iTTP patients with intolerance or refractoriness to rituximab. [ABSTRACT FROM AUTHOR]

Long-bone osteosclerosis is the most frequent manifestation, occurring in ~90% of patients.4 Osteosclerosis pathogenesis in ECD remains widely unknown. To summarise, ECD osteosclerosis can be reproduced in a xenografted mouse model with injection of patient-derived CD34 SP + sp cells, supporting that these cells could be at the origin of the disease. Erdheim-Chester disease long-bone osteosclerosis can be reproduced with a xenografted mouse model and its pathogenesis may involve dysregulation of bone metabolism key cytokines. [Extracted from the article]

(1) Background: Pediatric sarcoidosis is a rare and mostly severe disease. Very few pediatric series with a prolonged follow-up are reported. We aimed to evaluate the evolution of pediatric sarcoidosis in adulthood. (2) Material and methods: Patients over 18-years-old with a pediatric-onset sarcoidosis (≤15-year-old) who completed at least a three-year follow-up in French expert centers were included. Clinical information at presentation and outcome in adulthood were studied. (3) Results: A total of 52 patients were included (34 prospectively in childhood and 18 retrospectively in adulthood), with a mean age of 12 (±2.7) at diagnosis. The median duration time of follow-up was 11.5 years (range 3–44.5). Relapses mostly occurred during treatment decrease (84.5%), others within the three years after treatment interruption (9.1%), and rarely when the disease was stable for more than three years (6.4%). Sarcoidosis was severe in 11 (21.2%) in adulthood. Patients received a high corticosteroid cumulative dose (median 17,900 mg) for a median duration of five years (range 0–32), resulting in mostly mild (18; 35.3%) and rarely severe (2; 3.8%) adverse events. (4) Conclusions: Pediatric-onset sarcoidosis needed a long-term treatment in almost half of the patients. Around one fifth of pediatric-onset sarcoidosis patients had severe sarcoidosis consequences in adulthood. [ABSTRACT FROM AUTHOR]

Histiocytoses are disorders characterised by inflammation and the accumulation of cells derived from the monocyte and macrophage lineages, which results in tissue damage. Although they are often considered rare disorders with protean clinical manifestations, considerable advances in the understanding of their genetics have led to increased clinical recognition of these conditions, and fuelled further insights into their pathogenesis. In this Review, we describe insights into the cells of origin, molecular pathology, clinical features, and treatment strategies for some of the most common histiocytic disorders, including Langerhans cell histiocytosis, Erdheim-Chester disease, and Rosai-Dorfman disease. With the discovery of recurrent mutations affecting the mitogen-activated protein kinase and mTOR-AKT pathways in some of these histiocytoses, our understanding of these diseases has now evolved from the concept of a primary inflammatory condition to that of a clonal neoplastic disease. This understanding has led to the development of effective mechanism-based therapeutic strategies for patients with histiocytic diseases. [ABSTRACT FROM AUTHOR]

Summary: To calculate the prevalence of sinonasal and ear involvement in an Erdheim‐Chester disease (ECD) population, to describe the different ear, nose and throat (ENT) manifestations and to study the association between ENT involvement, other organ involvement, and BRAF mutations. We led a retrospective monocentric study in the national referral center for ECD. One hundred and sixty‐two patients with ECD and ENT data were included between January 1, 1980 and December 31, 2020. Ear and nose clinical and radiological findings were noted. We described and studied the prevalence of ENT involvement in ECD population. The association between sinonasal and ear involvement, other organ involvement, and BRAF mutations was calculated. The prevalence of ENT manifestations is around 45%. No clinical rhinologic or otologic signs were specific to ECD. Sinus imaging was abnormal in 70% of cases. A bilateral maxillary sinus frame osteosclerosis was highly specific of ECD. Associations were found between the sinus MRI imaging type and BRAF status, central nervous system involvement, cerebellum involvement and xanthelasma. Sinonasal or ear involvement is frequent in ECD and has specific imaging features for sinuses. Trial registration: #2011‐A00447‐34. [ABSTRACT FROM AUTHOR]

Although neurological manifestations and changes in brain volumes have been described in Erdheim-Chester disease (ECD), it remains unknown whether ECD may be associated with psychiatric symptoms and cognitive dysfunctions. We assessed the presence of psychiatric disorders, changes in temperaments and characters, and neuropsychological performances in 32 ECD patients (mean age = 59) younger than 70, not treated with interferon alpha during the last 6 months, and without other serious illnesses. ECD patients exhibited high level of past depressive disorder (80%) and anxiety disorder, especially agoraphobia (29%). They revealed personality changes, especially with high agreeableness (t = 3.18, p < 0.005) and high conscientiousness (t = 3.81, p < 0.001). Neuropsychological assessments showed impairments in attention (GZ: t = 16.12, p < 0.0001, KL: t = 37.01, p < 0.0001) and episodic memory performances (STIR: t = − 3.01, p = 0.006, LTFR: t = − 2.87, p = 0.008, LTIR: t = − 3.63, p = 0.001). Executive functions, such as flexibility, inhibitory control, were unimpaired. Although it remains to be clarified whether these psychiatric symptoms and cognitive impairments may impact the daily functioning and the quality of life, the present study highlights the need to consider cognitive and emotional states in ECD management. [ABSTRACT FROM AUTHOR]

Background and aims: RFC1-CANVAS and primary Sjögren syndrome (pSS) are among the most frequent causes of sensory ganglionopathy (SG) and can present simultaneously in a given patient, sharing confounding signs and symptoms. We describe the clinical characteristics of patients with SG due to CANVAS who were suspected of having or had received a previous diagnosis of pSS. Methods: Patients with SG and a genetically confirmed RFC1-CANVAS followed in our centre were ascertained and their personal history of pSS was collected. Results: Among the 71 patients with CANVAS, six patients (all females) had been diagnosed with pSS by their clinicians. In these six patients, the mean age at onset of the SG was 61 years, four patients describing gait instability and positive sensory symptoms, one only gait instability and one only positive sensory symptoms. Five patients had a history of chronic cough; signs at examination included a cerebellar syndrome (n = 3), vestibulopathy (n = 2), pes cavus (n = 3) and dysautonomia (n = 2). On neurophysiological examination, SG was generally severe and symmetrical. All patients presented a sicca syndrome, but only four patients had a confirmed pSS as per 2016 ACR-EULAR classification criteria. Four patients were treated but did not respond to immunosuppressive therapy, one suffering from side effects. Interpretation: The suspicion or diagnosis of pSS in a patient with SG should not exclude RFC1 expansion analysis, as a CANVAS diagnosis may dissuade the clinician from initiating or continuing immunosuppressive therapy, especially in unconfirmed pSS patients. Importantly, a sicca syndrome may lead to pSS misdiagnosis. [ABSTRACT FROM AUTHOR]

Langerhans cell histiocytosis (LCH) is a rare inflammatory myeloid neoplasm characterized by proliferation of tumor histiocytes that involves multiple organs including central nervous system. The physiopathologic process underlying degenerative neuro-LCH (i.e., DN-LCH) remains imperfectly settled. Since the main clinical features of DN-LCH are cerebellar ataxia and dysexecutive syndrome, eye movements might be disrupted and may help in disease diagnosis and monitoring. We retrospectively analyzed the medical records of twenty DN-LCH patients investigated using eye movement recording (EMR) in our hospital between 2015 and 2018. DN-LCH patients exhibited (i) abnormal gain in visually guided saccades including hypermetric saccades and excessive gain variability -45.0%-, (ii) increased mean antisaccade error rates -66.7%-, (iii) altered smooth pursuit -50.0%-, and (iv) excessive number of square wave jerks-25%- and gaze-evoked nystagmus. Our study suggests that DN-LCH patients present a peculiar pattern of eye movement impairments supporting cerebellar and prefrontal dysfunctions. As a non-invasive method, EMR could therefore be a useful tool for quantitative monitoring of DN-LCH patients. Further studies are warranted to support our findings. [ABSTRACT FROM AUTHOR]

Objectives: Systemic rheumatic diseases (SRDs) are a group of inflammatory disorders that can need intensive care unit (ICU) admission during a flare-up, requiring administration of immunosuppressants. We undertook this study to determine the frequency, outcome, and occurrence associated factors of infections in flare-up SRD patients receiving immunosuppressant. Methods: Monocenter, a retrospective study including SRD patients admitted to ICU for a flare-up requiring immunosuppressant from 2004 to 2019. The primary endpoint was in-ICU-acquired infections. Results: Ninety-eight patients (female/male ratio: 1.6; mean age at admission: 39.5 ± 17.4 years) were admitted to the ICU for a SRD flare-up, inaugural in 61.2% cases. A specific treatment was given to every patient: corticosteroids 100%, cyclophosphamide 45.9%, plasma exchange 46.9%. Ninety-five infections occurred in 35 (36%) patients mainly pneumonias. The overall in-hospital mortality was 17.3%, and 46% of patients with a nosocomial infection died during their ICU stay. The logistic regression multivariable model retained renal replacement therapy and mechanical ventilation as independent predictors of infection. Conclusion: In-ICU-acquired infection in SRD flare-up is a frequent event associated with organ failures but not with in-ICU use of immunosuppressants. These data suggest that the fear of infection should not withhold a careful in-ICU use of immunosuppressive drugs. Key Points • In-ICU infections are frequent in flare-up systemic rheumatic disease patients. • Infections are associated with increased mortality. • Cyclophosphamide given in ICU was not independently associated with infection. • Severe neutropenia occurred in 27% of patients receiving cyclophosphamide in ICU. [ABSTRACT FROM AUTHOR]

Histiocytoses are rare disorders of unknown origin with highly heterogeneous prognosis. BRAFV600E gain-of-function mutations have been observed in 57% of cases of Langerhans cell histiocytosis (LCH) and 54% of cases of Erdheim-Chester disease (ECD), but not in other types of histiocytoses. Targeted therapy with an inhibitor of mutated BRAF (vemurafenib) improves survival of patients with melanoma. Here, we report vemurafenib treatment of 3 patients with multisystemic and refractory ECD carrying the BRAFV600E mutation; 2 also had skin or lymph node LCH involvement. The patients were assessed clinically, biologically (CRP values), histologically (skin biopsy), and morphologically (positron emission tomography [PET], computed tomography and magnetic resonance imaging). For all patients, vemurafenib treatment led to substantial and rapid clinical and biologic improvement, and the tumor response was confirmed by PET, computed tomography, and/or magnetic resonance imaging 1 month after treat- ment initiation. For the first patient treated, the PET response increased between months 1 and 4 of treatment. The treatment remained effective after 4 months of follow-up although persistent disease activity was still observed. Treatment with vemurafenib, a newly approved BRAF inhibitor, should be considered for patients with severe and refractory BRAFV600E histiocytoses, particularly when the disease is life-threatening. [ABSTRACT FROM AUTHOR]

Antiphospholipid syndrome (APS) is a rare autoimmune disease characterized by thromboses at various sites and obstetric events associated with the persistent presence of antiphospholipid antibodies. The identification of clinical phenotypes in APS patients is a clinical need. In this study, we aimed to determine the clinical phenotypes of APS patients through an unsupervised analysis of two well-characterized cohorts of APS patients. APS phenotypes were defined by an ascending hierarchical cluster analysis to identify preferential associations between 18 types of organ involvement and clinical characteristics. This analysis was performed on an initial multi-center cohort of 1000 patients, with validation in a replication cohort of 435 patients. The hierarchical analysis identified three APS phenotypes in both the initial and replication cohorts: an obstetric phenotype (n = 259 and n = 74 patients, respectively), a venous thrombosis phenotype, accounting for the largest number of patients (n = 461 and n = 297 patients, respectively), and a skin-central nervous system-heart phenotype (n = 280 and n = 64 patients, respectively). The clinical characteristics of the patients differed significantly between the three phenotypes, but there was no difference in antiphospholipid antibody profile between the groups. We identified three phenotypes of APS defined based on preferential associations of organ involvements and differences in presentation. These observations may help clinicians to detect organ involvement and to manage treatment. • Highlights "Phenotypes in antiphospholipid syndrome: a hierarchical cluster analysis based on two independent databases". • Three phenotypes of Antiphospholipid Syndrome defined based on preferential associations of organ involvements. • By performing an analysis on an initial cohort of 1000 patients, with validation in a replication cohort of 435 patients. • These results may help clinicians to detect organ involvement and to manage treatment. [ABSTRACT FROM AUTHOR]

Background: Susac syndrome is a very rare cerebral small vessel disease, which can leave patients with cognitive impairment. We aimed at evaluating processing speed slowing, executive dysfunction and apathy and their relationships with whole brain and callosal atrophy. Methods: Patients with Susac syndrome included in a prospective observational cohort study were evaluated, while clinically steady-state, with standardized brain MRI and a neuropsychological battery specifically designed to capture minimal cognitive alterations in non-disabled young patients. Brain volume and corpus callosum area were measured using 3D-T1 sequences, repeatedly overtime. Relationships between neuropsychological data and brain volumetric measures obtained the same day were tested with linear regression while controlling for sex, age, level of education, scores of depression and of apathy. Results: Nineteen patients aged 37.5 ± 10.5 years were included. Mean follow-up time was 2.6 ± 1.3 years (5.8 ± 2.2 evaluations). While Montreal Cognitive Assessment scores were 25.1 ± 3.6, processing speed slowing was obvious (Trail Making Test version A: 43.1 ± 16.2 s; version B: 95.5 ± 67.9 s; reaction time: 314.6 ± 79.6 ms). Brain and corpus callosum atrophy was striking. No relationship was found between cognitive performances and brain volume or corpus callosum area. Conclusion: Patients with Susac syndrome show largely preserved global cognitive functions but important processing speed alterations. Although brain and corpus callosum area atrophy is prominent and evolving, we did not find any relationship with cognitive alterations, questioning the mechanisms underlying cognitive alterations in these patients. Trial registration: Clinical Trial Registration-URL: https://www.clinicaltrials.gov Unique Identifier: NCT01481662 [ABSTRACT FROM AUTHOR]

Background: Destombes-Rosai-Dorfman disease (RDD) is a rare multisystemic histiocytosis. Pulmonary involvement during RDD has been poorly described. The goal of this study was to examine the clinical presentations, radiological features, and outcomes of 15 patients with RDD and lung involvement.Methods: The cases of RDD with lung involvement were extracted from the French National Histiocytosis registry. Efficacy of the MEK inhibitor cobimetinib in treating lung disease was evaluated with an 18fluorodeoxyglucose PET scanner and chest CT scans.Results: Fifteen patients (six women; median age, 40 years at RDD diagnosis) were included. All patients had evidence of systemic disease with extrapulmonary localizations of the disease (lymphadenopathy [n = 12], skin [n = 9], bones [n = 6], retroperitoneal involvement [n = 3], sinuses [n = 3], parotid gland [n = 2], submandibular gland [n = 1], and breast [n = 1]). Presenting symptoms were dominated by dyspnea and dry cough in seven patients. Restrictive physiology was observed in two of five patients. BAL showed lymphocytosis in one of five cases. Eight patients received corticosteroids, all but one with variable immunosuppressive or immunomodulatory therapies. Two patients received cobimetinib for severe lung disease, with dramatic pulmonary metabolic and tumoral responses. Two patients died during follow-up: one of hemoptysis, and the other of an unrelated cerebral tumor.Conclusions: Pulmonary involvement in RDD is rare, proteiform, and sometimes severe. The MEK inhibitor cobimetinib can lead to dramatic responses. [ABSTRACT FROM AUTHOR]