Characteristics and outcomes associated with CD2 and CD25 expression on bone marrow mast cells in patients with systemic mastocytosis.

Not available.

[Allogeneic haematopoietic stem cell transplantation induced remission of periarteritis nodosa associated with azacytidine-refractory myelodysplastic syndrome]. / Mise en rémission par allogreffe de cellules souches hématopoïétiques d'une péri artérite noueuse associée à un syndrome myélodysplasique réfractaire à l'azacytidine.

INTRODUCTION: Periarteritis nodosa (PAN) is a vasculitis affecting medium-vessel and may be associated with myelodysplastic syndrome. This association needs a simultaneous treatment of the vascular and the hematological disease. However limited data are available on the benefit of hematological treatment, and in particular allogeneic stem cell transplantation, in this situation. CASE REPORT: A 32-year-old patient with refractory periarteritis nodosa and simultaneous myelodysplastic syndrome, was treated with chemotherapy followed by hematopoietic stem cell allograft. The symptoms relating to PAN improved, allowing to decrease the dose of prednisone down to 5mg/d. However, a hematological relapse occurred two months later leading to the patient's death. CONCLUSION: Hematopoietic stem cell allograft may represent a therapeutic option in the management of severe or refractory autoimmune diseases when the hematological indication is retained.

Gastrointestinal disorders in systemic sclerosis: cluster analysis and prognosis from a French prospective cohort.

OBJECTIVES: The gastrointestinal tract (GIT) is frequently involved in systemic sclerosis (SSc) and is responsible for alteration of quality of life. Many complications can occur, including chronic intestinal pseudo-obstruction, digestive haemorrhage and small-intestinal bacterial overgrowth. Since early development of organ failure is associated with poor prognosis, we need to identify risk factors associated with severe GIT involvement to prevent severe forms of the disease. METHODS: We conducted an observational prospective study, which included 90 SSc patients from December 2019 to September 2021. We collected questionnaires about digestive manifestations and quality of life, blood and stool samples, and performed imaging. At inclusion and throughout the study we assessed the occurrence of malnutrition and severe GIT disorders. We performed statistical analysis to highlight eventual risk factors associated with digestive manifestations, including hierarchical cluster analysis. RESULTS: A majority of our patients had gastro-oesophageal manifestations (93.3%), followed by intestinal manifestations (67.8%) and anorectal manifestations (18.9%). We found a correlation between anorectal disorders and cardiac disease, and between gastro-oesophageal involvement and impaired pulmonary function tests. Smoking was significantly associated with occurrence of severe GIT disorders. Malnutrition was frequent and associated with more cardiac and pulmonary disease. Cluster analysis identified three groups of patients, including one cluster with cardiac and digestive involvement. CONCLUSIONS: GIT manifestations are frequent and severe in SSc. Smoking appears to be associated with severe disease. Anorectal manifestations may be associated with cardiac disease, but we need more studies to validate these results.

Prevalence and association of placental lesions with obstetrical features and outcome: data from French prospective study.

Purpose: Since the Consensus Statement diffused by the Amsterdam Placental Workshop Group, knowledge of the meaning of placental vascular malperfusion has become essential in the unavoidable analysis of obstetrical history in a patient followed for autoimmune disease or any other maternal comorbidity. We aimed to analyse the prevalence of various placental lesions from a 6-months prospective observational study and to correlate the various placental profiles to obstetrical outcome, maternal diseases and pregnancy treatments. The frequency of foetal vascular malperfusion lesion could be estimated at 8.7%, in our population and to understand its neonatal associations. Methods: The study groups consisted of 208 consecutive women which ended the pregnancy and have placental analysis during the period of the study. Results: From December 2015 to October 2017, from overall 4398 delivered pregnancies in university obstetrical department, 208 (4.7%) placental analysis have been done and included in the study. The placental analysis have been done for vascular obstetrical complications during the pregnancy (n = 106; 51%), unexplained abnormal foetal heart rate tracings (n = 59; 28,3%), suspicion of intra-amniotic infection (n = 12; 5,7%%), term new-borns Apgar score <7 or arterial cord blood pH ≤ 7 (n = 7; 3,5%), spontaneous preterm delivery (n = 19; 9,1%), intrahepatic cholestasis of pregnancy (n = 5; 2,4%). An adverse obstetrical event was noted in 87 cases (42%): preeclampsia or HELLP syndrome (n = 15; 7%), FGR (n = 59; 28%), gestational diabetes (n = 33; 16%) and gestational hypertension (n = 19; 9%). Placental histological analysis showed abnormal vascular features in 159 cases (76%), inflammatory features in 16 placentas (8%), vascular and inflammatory features in 10 cases (4%), chorioamnionitis in 38 cases (18%) and absence of any abnormality in 43 cases (21%). A cluster analysis of histological features allowed distinguishing three placental patterns: a normal pattern characterised by the absence of any placental lesions, an inflammatory pattern characterised by the presence of villitis and/or chronic intervillositis; a vascular pattern with the presence of thrombosis, maternal floor infarct with massive perivillous fibrin deposition, infarction and chronic villositis hypoxia. Women with inflammatory placental profile have significantly increased frequencies of tobacco use (50% vs. 9%; P = 0.03), pathological vascular Doppler (50% vs. 5%; P = 0.001), FGR (100% vs. 14%; P = 0.0001) and oligohydramnios (67% vs. 5%; P = 0.0001) than those with normal placentas. A higher rate of vascular or inflammatory lesion were observed in women with Hypertensive disorder of pregnancy, where as those with inflammatory pattern have significantly more frequent FGR (100% vs 34%; P = 0.02) and oligohydramnios (67% vs 5%; P = 0.0002). Conclusion: The placenta analysis is important to understand the origin of adverse obstetrical outcome and the risk for subsequent pregnancy.

Kidney involvement in myelodysplastic syndromes.

Introduction: The objective of this study was to describe kidney involvement in patients with myelodysplastic syndromes (MDS), their treatments, and outcomes. Methods: We conducted a multicenter retrospective study in seven centers, identifying MDS patients with acute kidney injury (AKI), chronic kidney disease (CKD), and urine abnormalities. Results: Fifteen patients developed a kidney disease 3 months after MDS diagnosis. Median urine protein-to-creatinine ratio was 1.9 g/g, and median serum creatinine was 3.2 mg/dL. Ten patients had AKI at presentation, and 12 had extra-renal symptoms. The renal diagnoses included anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), ANCA negative vasculitis, C3 glomerulonephritis, immune complex-mediated glomerulonephritis, polyarteritis nodosa, and IgA vasculitis. All patients but one received a specific treatment for the MDS-associated kidney injury. The effect of MDS treatment on kidney injury could be assessed in six patients treated with azacitidine, and renal function evolution was heterogenous. After a median follow-up of 14 months, four patients had CKD stage 3, five had CKD stage 4, and three had end stage kidney disease. On the other hand, three evolved to an acute myeloid leukemia and three died. Compared to 84 MDS controls, patients who had kidney involvement were younger, had a higher number of dysplasia lineages, and were more eligible to receive hypomethylating agents, but no survival difference was seen between the two groups. Compared to 265 AAV without MDS, the ten with MDS-associated pauci-immune vasculitis were older, ANCA serology was more frequently negative, and more cutaneous lesions were seen. Conclusion: The spectrum of kidney injuries associated with MDS is mostly represented by vasculitis with glomerular involvement, and especially AAV.

Intravenous Immunoglobulins for Recurrent Chronic Histiocytic Intervillositis: A Series of Case Studies.

INTRODUCTION: Chronic histiocytic intervillositis (CHI) is a rare inflammatory placental disease characterized by diffuse infiltration of monocytes into the intervillous space and is associated with adverse pregnancy outcomes. No treatment is currently validated and although in some small reports, steroids with hydroxychloroquine have been described. There are no data for other therapies in refractory cases. PATIENTS AND METHODS: We here report four cases of patients with a history of CHI treated with immunoglobulins during a subsequent pregnancy. The four patients with recurrent CHI had failed to previous immunomodulatory therapies with steroids and hydroxychloroquine. All patients had at least four pregnancy losses with histopathological confirmation of CHI for at least one pregnancy loss. The usual pregnancy-loss etiology screening and immunological screening were negative for all the patients. RESULTS: For three patients, intravenous immunoglobulins were initiated at the ßHCG positivity at 1 g/kg every 15 days until delivery. In one case with combined therapy since the beginning of the pregnancy, intravenous immunoglobulins were introduced at 20 WG because of severe growth restriction. Two patients had live births at 36 WG and one patient at 39 WG. One patient, who presented early first-trimester hypertension and severe placental lesions, failed to intravenous immunoglobulins and had a pregnancy loss at 15 WG. CONCLUSION: This is the first report demonstrating the potential benefit of intravenous immunoglobulins in recurrent chronic intervillositis. Larger studies are needed to confirm this potential benefit for patients presenting severe cases of recurrent CHI.

Hydroxychloroquine in recurrent pregnancy loss: data from a French prospective multicenter registry.

STUDY QUESTION: What are the outcomes of pregnancies exposed to hydroxychloroquine (HCQ) in women with a history of recurrent pregnancy loss (RPL), and what factors predict the course of these pregnancies beyond the first trimester? SUMMARY ANSWER: In our cohort of pregnancies in women with a history of RPL exposed to HCQ early in pregnancy, we found that the only factor determining the success of these pregnancies was the number of previous miscarriages. WHAT IS KNOWN ALREADY: Dysregulation of the maternal immune system plays a role in RPL. HCQ, with its dual immunomodulating and vascular protective effects, is a potential treatment for unexplained RPL. STUDY DESIGN, SIZE, DURATION: The FALCO (Facteurs de récidive précoce des fausses couches) registry is an ongoing French multicenter infertility registry established in 2017 that includes women (aged from 18 to 49 years) with a history of spontaneous RPL (at least three early miscarriages (≤12 weeks of gestation (WG)) recruited from several university hospitals. PARTICIPANTS/MATERIALS, SETTING, METHODS: Spontaneous pregnancies enrolled in the FALCO registry with an exposure to HCQ (before conception or at the start of pregnancy) were included. Pregnancies concomitantly exposed to tumor necrosis factor inhibitors, interleukin-1 and -2 inhibitors, intravenous immunoglobulin, and/or intravenous intralipid infusion, were excluded. Concomitant treatment with low-dose aspirin (LDA), low-molecular weight heparin (LMWH), progesterone, and/or prednisone was allowed. All patients underwent the recommended evaluations for investigating RPL. Those who became pregnant received obstetric care in accordance with French recommendations and were followed prospectively. The main endpoint was the occurrence of a pregnancy continuing beyond 12 WG, and the secondary endpoint was the occurrence of a live birth. MAIN RESULTS AND THE ROLE OF CHANCE: One hundred pregnancies with HCQ exposure in 74 women were assessed. The mean age of the women was 34.2 years, and the median number of previous miscarriages was 5. Concomitant exposure was reported in 78 (78%) pregnancies for prednisone, 56 (56%) pregnancies for LDA, and 41 (41%) pregnancies for LMWH. Sixty-two (62%) pregnancies ended within 12 WG, the other 38 (38%) continuing beyond 12 WG. The risk of experiencing an additional early spontaneous miscarriage increased with the number of previous miscarriages, but not with age. The distributions of anomalies identified in RPL investigations and of exposure to other drugs were similar between pregnancies lasting ≤12 WG and those continuing beyond 12WG. The incidence of pregnancies progressing beyond 12 WG was not higher among pregnancies with at least one positive autoantibody (Ab) (i.e. antinuclear Ab titer ≥1:160, ≥1 positive conventional and/or non-conventional antiphospholipid Ab, and/or positive results for ≥1 antithyroid Ab) without diminished ovarian reserve (18/51, 35.3%) than among those without such autoantibody (18/45, 40.0%) (P = 0.63). Multivariate analysis showed that having ≤4 prior miscarriages was the only factor significantly predictive for achieving a pregnancy > 12 WG, after adjustment for age and duration of HCQ use prior to conception (adjusted odds ratio (OR) = 3.13 [1.31-7.83], P = 0.01). LIMITATIONS, REASONS FOR CAUTION: Our study has limitations, including the absence of a control group, incomplete data for the diagnostic procedure for RPL in some patients, and the unavailability of results from endometrial biopsies, as well as information about paternal age and behavioral factors. Consequently, not all potential confounding factors could be considered. WIDER IMPLICATIONS OF THE FINDINGS: Exposure to HCQ in early pregnancy for women with a history of RPL does not seem to prevent further miscarriages, suggesting limited impact on mechanisms related to the maternal immune system. STUDY FUNDING/COMPETING INTEREST(S): The research received no specific funding, and the authors declare no competing interests. TRIAL REGISTRATION NUMBER: clinicaltrial.gov NCT05557201.

Induction of regulatory T cells and efficacy of low-dose interleukin-2 in systemic sclerosis: interventional open-label phase 1-phase 2a study.

BACKGROUND: Systemic sclerosis (SSc) is a chronic autoimmune disease, with impaired immune response, increased fibrosis and endothelial dysfunction. Regulatory T cells (Tregs), which are essential to control inflammation, tissue repair and autoimmunity, have a decreased frequency and impaired function in SSc patients. Low-dose interleukin-2 (IL-2LD) can expand and activate Tregs and has, therefore, a therapeutic potential in SSc. OBJECTIVE: We aimed to assess the safety and biological efficacy of IL-2LD in patients with SSc. METHODS: As part of the TRANSREG open-label phase IIa basket trial in multiple autoimmune diseases, we studied nine patients with SSc without severe organ involvement. Patients received 1 million international units (MIU)/day of IL-2 for 5 days, followed by fortnightly injections for 6 months. Laboratory and clinical evaluations were performed between baseline and month 6. RESULTS: At day 8, the primary endpoint (Treg frequency) was reached with a 1.8±0.5-fold increase of Treg levels among CD4+ T lymphocytes (p=0.0015). There were no significant changes in effector T cells nor in B cells. IL-2LD was well tolerated, and no serious adverse events related to treatment occurred. There was a globally stable measurement in the modified Rodnan skin score and Valentini score at month 6. Disease activity and severity measures, the quality of life evaluated by EuroQL-5D-5L and pulmonary function test parameters remained stable during the study period. CONCLUSION: IL-2LD at a dosage of 1 MIU/day safely and selectively activates and expands Tregs. Clinical signs remain stable during the study period. This opens the door to properly powered phase II efficacy trials investigating IL-2LD therapeutic efficacy in SSc.

Autoimmune cytopenia and Kabuki syndrome in paediatrics: Insights in 11 patients.

Kabuki syndrome (KS) is now listed in the Human Inborn Errors of Immunity (IEI) Classification. It is a rare disease caused by KMT2D and KDM6A variants, dominated by intellectual disability and characteristic facial features. Recurrently, pathogenic variants are identified in those genes in patients examined for autoimmune cytopenia (AIC), but interpretation remains challenging. This study aims to describe the genetic diagnosis and the clinical management of patients with paediatric-onset AIC and KS. Among 11 patients with AIC and KS, all had chronic immune thrombocytopenic purpura, and seven had Evans syndrome. All had other associated immunopathological manifestations, mainly symptomatic hypogammaglobinaemia. They had a median of 8 (5-10) KS-associated manifestations. Pathogenic variants were detected in KMT2D gene without clustering, during the immunological work-up of AIC in three cases, and the clinical strategy to validate them is emphasized. Eight patients received second-line treatments, mainly rituximab and mycophenolate mofetil. With a median follow-up of 17 (2-31) years, 8/10 alive patients still needed treatment for AIC. First-line paediatricians should be able to recognize and confirm KS in children with ITP or multiple AIC, to provide early appropriate clinical management and specific long-term follow-up. The epigenetic immune dysregulation in KS opens exciting new perspectives.

Efficacy and Safety of Rituximab-Based Treatments in Angioedema With Acquired C1-Inhibitor Deficiency.

BACKGROUND: Angioedema (AE) due to acquired C1-inhibitor (C1-INH) deficiency (AAE-C1-INH) is related to excessive consumption of C1-INH or to anti-C1-INH antibodies, and is frequently associated with lymphoproliferative syndromes or monoclonal gammopathies. Standard of care for prophylactic treatment in this condition is not established. Rituximab may be effective to prevent attacks, especially if the lymphoid hemopathy is controlled, but data are scarce. OBJECTIVE: To evaluate efficacy of rituximab in AAE-C1-INH. METHODS: A retrospective multicenter study was carried out in France, including patients with AAE-C1-INH treated with rituximab between April 2005 and July 2019. RESULTS: Fifty-five patients with AAE-C1-INH were included in the study, and 23 of them had an anti-C1-INH antibody. A lymphoid malignancy was identified in 39 patients, and a monoclonal gammopathy in 9. There was no associated condition in 7 cases. Thirty patients received rituximab alone or in association with chemotherapy (n = 25). Among 51 patients with available follow-up, 34 patients were in clinical remission and 17 patients had active AE after a median follow-up of 3.9 years (interquartile range, 1.5-7.7). Three patients died. The presence of anti-C1-INH antibodies was associated with a lower probability of AE remission (hazard ratio, 0.29 [95% CI, 0.12-0.67]; P = .004). Relapse was less frequent in patients with lymphoma (risk ratio, 0.27 [95% CI, 0.09-0.80]; P = .019) and in patients treated with rituximab and chemotherapy (risk ratio, 0.31 [95% CI, 0.12-0.79]; P = .014). CONCLUSIONS: Rituximab is an efficient and well-tolerated therapeutic option in AE, especially in lymphoid malignancies and in the absence of detectable anti-C1-INH antibodies.

Massive perivillous fibrin deposition: Diagnosis, obstetrical features, and treatment.

MPVFD (Massive perivillous fibrin deposition) is placental lesion characterized by extensive massive deposits of fibrin in the intervillous space, extending over at least 25 % of the placental volume. Currently, this pathology can only be detected through histopathological examination of the placenta after a pregnancy has ended. The underlying mechanisms are poorly studied, there is no biomarker available for the diagnosis of MPVFD and treatment protocols are experimental and still lacking. The objective of this study is to systematically review the literature on the associated clinicopathologic features, treatment, and prognosis of MPVFD. We ended up with 17 studies, of these 12 studies were considered relevant for this article and included in the final analysis. All studies reporting MPVFD are retrospective. MPVFD is associated with recurrent miscarriage, intra uterine fetal death (IUFD), intra uterine growth restriction (IUGR) and preterm delivery. The prevalence in pregnancies with a delivery after 22 weeks of gestation was at 1.1 % and even higher to 2.7 % in recurrent early miscarriages. The reported risk of fetal death in MPVFD ranges mainly from 15 to 80 %. Preterm delivery is spontaneous in 50 to 70 % of cases and induced by of a severe intrauterine growth restriction (IUGR) in 30 to 50 % of cases depending on the study. Its causes and treatment are still poorly understood, although several avenues have been explored. This review summarizes current understanding of the prevalence, diagnostic features, clinical consequences, immune pathology, and potential prophylaxis against recurrence in this chronic inflammatory placental syndrome.

Serious infections in patients with VEXAS syndrome: data from the French VEXAS registry.

INTRODUCTION: Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is an acquired autoinflammatory monogenic disease with a poor prognosis whose determinants are not well understood. We aimed to describe serious infectious complications and their potential risk factors. METHODS: Retrospective multicentre study including patients with VEXAS syndrome from the French VEXAS Registry. Episodes of serious infections were described, and their risk factors were analysed using multivariable Cox proportional hazards models. RESULTS: Seventy-four patients with 133 serious infections were included. The most common sites of infection were lung (59%), skin (10%) and urinary tract (9%). Microbiological confirmation was obtained in 76%: 52% bacterial, 30% viral, 15% fungal and 3% mycobacterial. Among the pulmonary infections, the main pathogens were SARS-CoV-2 (28%), Legionella pneumophila (21%) and Pneumocystis jirovecii (19%). Sixteen per cent of severe infections occurred without any immunosuppressive treatment and with a daily glucocorticoid dose ≤10 mg. In multivariate analysis, age >75 years (HR (95% CI) 1.81 (1.02 to 3.24)), p.Met41Val mutation (2.29 (1.10 to 5.10)) and arthralgia (2.14 (1.18 to 3.52)) were associated with the risk of serious infections. JAK inhibitors were most associated with serious infections (3.84 (1.89 to 7.81)) compared with biologics and azacitidine. After a median follow-up of 4.4 (2.5-7.7) years, 27 (36%) patients died, including 15 (56%) due to serious infections. CONCLUSION: VEXAS syndrome is associated with a high incidence of serious infections, especially in older patients carrying the p.Met41Val mutation and treated with JAK inhibitors. The high frequency of atypical infections, especially in patients without treatment, may indicate an intrinsic immunodeficiency.

Chronic Myelomonocytic Leukemia Patients With Lysozyme Nephropathy and Renal Infiltration Display Markers of Severe Disease.

Introduction: Chronic myelomonocytic leukemia (CMML) is a hematologic disorder that is an overlap syndrome between myelodysplastic syndromes and myeloproliferative neoplasms, and can be associated with autoimmune and inflammatory diseases. This study aimed to describe kidney involvement in patients with CMML, their treatments, and outcomes. Methods: We conducted a French and American multicenter retrospective study in 15 centers, identifying patients with CMML with acute kidney injury (AKI), chronic kidney disease (CKD), and urine abnormalities. Results: Sixteen patients (males, n = 14; median age 76.5 years [71.9-83]) developed a kidney disease 6 months [1.6-25.6] after the diagnosis of CMML. At the time of kidney disease diagnosis, median urinary protein-to-creatinine ratio was 2 g/g [1.25-3.4], and median serum creatinine was 2.26 mg/dl [1.46-2.68]. Fourteen patients (87.5%) underwent a kidney biopsy, and the 2 main pathological findings were lysozyme nephropathy (56%) and renal infiltration by the CMML (37.5%). Ten patients received a new treatment following the CMML-associated kidney injury. Among patients with monitored kidney function, and after a median follow-up of 15 months [9.9-34.9], 4 patients had CKD stage 3, 4 had CKD stage 4, 1 had an end-stage kidney disease. In our patient series, 2 patients evolved to an acute myeloid leukemia (AML), and 5 died. Compared with 116 CMML controls, patients who had a kidney involvement had a higher monocyte count (P < 0.001), had more CMML-1 (P = 0.005), were more susceptible to develop an AML (P = 0.02), and were more eligible to receive a specific hematologic treatment, with hydroxyurea, or hypomethylating agents (P < 0.001), but no survival difference was seen between the 2 groups (P = 0.6978). Conclusion: In this cohort of patients with CMML with a kidney injury, the 2 most frequent renal complications were lysozyme-induced nephropathy and renal infiltration by the CMML. Kidney involvement should be closely monitored in patients with CMML.

Heart and systemic sclerosis-findings from a national cohort study.

OBJECTIVES: Heart involvement is one of the leading causes of death in systemic sclerosis (SSc). The prevalence of SSc-related cardiac involvement is poorly known. Our objective was to investigate the prevalence and prognosis burden of different heart diseases in a nationwide cohort of patients with SSc. METHODS: We used data from a multicentric prospective study using the French SSc national database. Focusing on SSc-related cardiac involvement, we aimed to determine its incidence and risk factors. RESULTS: Over the 3528 patients with SSc 312 (10.9%) had SSc-related cardiac involvement at baseline. They tended to have a diffuse SSc subtype more frequently, more severe clinical features, and presented more cardiovascular risk factors. From the 1646 patients available for follow-up analysis, SSc-related cardiac involvement was associated with an increased risk of death. There was no significant difference in overall survival between SSc-related cardiac involvement, ischaemic heart disease or pulmonary arterial hypertension. Regarding survival analysis, 98 patients developed SSc-related cardiac involvement at five years (5-year event rate: 11.15%). Regarding reduced LVEF < 50% and left ventricular diastolic dysfunction, the 5-year event rate was 2.49% and 5.84% respectively. Pericarditis cumulative incidence at five years was 3%. Diffuse SSc subtype was a risk factor for SSc-related cardiac involvement and pericarditis. Female sex was associated with less left ventricular diastolic dysfunction incidence. CONCLUSIONS: Our results describe the incidence and prognostic burden of SSc-related cardiac involvement at a large scale, with gender and diffuse SSc subtype as risk factors. Further analyses should assess the potential impact of treatment on these various cardiac outcomes.

[Dysimmune manifestations associated with myelodysplastic neoplasms and chronic myelomonocytic leukaemias]. / Manifestations dysimmunitaires associées aux syndromes myélodysplasiques et leucémies myélomonocytaires chroniques.

Systemic inflammatory or autoimmune diseases (SIAD) are observed in up to a quarter of patients with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML), with a broad clinical spectrum including asymptomatic biological abnormalities, isolated inflammatory clinical manifestations (recurrent fever, arthralgia, neutrophilic dermatoses…) or identified systemic diseases (giant cell arteritis, recurrent polychondritis…). Recent advances in molecular biology have shed new light on the pathophysiological mechanisms that link inflammatory manifestations and myeloid hemopathies, particularly in VEXAS syndrome following the identification of somatic mutations in the UBA1 gene, or in neutrophilic dermatoses with the concept of myelodysplasia cutis. Although the presence of SIAD does not seem to affect overall survival or the risk of transformation into acute myeloid leukemia, their treatment remains a challenge given the frequent high level of corticosteroid dependence as well as the poor efficacy and tolerance (cytopenias, infections) of conventional immunosuppressive agents. Recent prospective data supports the interest of a therapeutic strategy using demethylating agents and notably azacitidine to target the pathological clone.

[Takayasu's arteritis]. / Artérite de Takayasu.

TAKAYASU'S ARTERITIS. Takayasu's arteritis is an inflammatory panarteritis of the large vessels, preferentially affecting the aorta, its main branches, and the pulmonary arteries. Its incidence is estimated at 1.11 cases per million person-years, with a female predominance. The disease is classically characterized by the succession of two phases: a pre-occlusive inflammatory phase that may go unnoticed and an occlusive phase characterized by ischemic vascular symptoms because of parietal arterial lesions such as stenosis, occlusion or aneurysm. The diagnosis is based on clinical, biological and morphological findings. When available, pathological examination reveals a predominantly medial-adventitial, segmental and focal granulomatous panarteritis. Treatment consists of administering corticosteroid therapy and often immunosuppressants, or even biotherapies, managing cardiovascular risk factors, and managing vascular complications.

ARTÉRITE DE TAKAYASU. L'artérite de Takayasu est une panartérite inflammatoire des gros vaisseaux touchant préférentiellement l'aorte et ses branches principales ainsi que les artères pulmonaires. On estime son incidence annuelle à 1,11 cas par million de personnes, avec une prédominance féminine. Il est classiquement observé deux phases successives : une phase inflammatoire préocclusive pouvant passer inaperçue, puis une phase occlusive, caractérisée par des symptômes vasculaires ischémiques, conséquence des lésions artérielles pariétales à type de sténose, occlusion ou anévrisme. Le diagnostic repose sur un faisceau d'arguments cliniques, biologiques et morphologiques. Lorsqu'il est accessible, l'examen anatomopathologique retrouve un aspect de panartérite granulomateuse à prédominance médio-adventitielle, segmentaire et focale. Le traitement consiste en l'administration d'une corticothérapie et souvent d'immunosuppresseurs, ainsi qu'en la prise en charge des facteurs de risque cardiovasculaire afin de prévenir les complications vasculaires à plus long terme.