[Health status and quality of life in ß-thalassemia adults in Marseille, France]. / État de santé et qualité de vie des patients ß-thalassémiques adultes à Marseille, France.

INTRODUCTION: The life expectancy of ß-thalassemia patients has increased over the last 20 years. In this study, we evaluated the current health status and quality of life of these patients managed in a reference center in Marseille. METHODS: This is a single-center, descriptive study conducted between June and August 2019 in patients over 18 years of age with ß-thalassemia major or intermedia. Clinical and paraclinical data were collected retrospectively and the SF-36 health survey questionnaire was proposed to each patient. RESULTS: 43 of 64 selected patients were included and divided into 2 groups: 35 patients with transfusion-dependent ß-thalassemia and 8 patients with non-transfusion-dependent ß-thalassemia. Liver iron overload is the most frequent complication, present in 80% of transfusion-dependent and 62.5% of non-transfusion-dependent patients. Cardiac iron overload is present only in the transfusion dependent ß-thalassemia group (20%). Hypogonadotropic hypogonadism remains the most common endocrine disorder (41.9%) followed by osteoporosis (37.2%). Among the 31 patients who completed the SF-36 questionnaire, physical and mental quality of life scores were lowered in transfusion dependent (respectively 42.7 and 46.8) as in non-transfusion-dependent patients (respectively 43.8 and 28.9). CONCLUSION: Despite an improvement in medical care, our patients with ß-thalassemia show an alteration in their quality of life that will need to be characterized in the entire French cohort.

[High anti-topoisomerase-1 autoantibodies levels are associated with the extension of skin fibrosis and vascular progression in patients with systemic sclerosis]. / Des taux élevés d'auto-anticorps anti-topo-isomérase-1 sont associés à l'extension de la fibrose cutanée et à la progression vasculaire chez les patients atteints de sclérodermie systémique.

BACKGROUND: Anti-centromere antibodies, anti-topoisomerase-1 antibodies (ATA), and anti-RNA-polymerase III antibodies are three Systemic Sclerosis (SSc)-specific autoantibodies. Their detection is helpful in determining the prognosis. We aimed to evaluate whether ATA levels were associated with disease severity at diagnosis or disease progression during follow-up in ATA positive patients. METHODS: We conducted a single-centre French retrospective observational study, between 2014 and 2021. ATA positive patients fulfilling the ACR/EULAR 2013 classification criteria for SSc with a minimal follow-up of 1 year and 2 ATA dosages were included. SSc patients with high IgG ATA levels at baseline (>240IU/mL) were compared with SSc patients with low levels (≤240IU/mL), at inclusion and at 1 and 3 years. A variation of at least 30 % of ATA levels was considered significant. RESULTS: Fifty-nine SSc patients were included and analysed. There was a predominance of women and of patients with diffuse interstitial lung disease. Patients with high ATA levels exhibited a higher skin sclerosis assessed by the modified Rodnan skin score (P=0.0480). They had a lower carbon monoxide transfer coefficient (P=0.0457), a lower forced vital capacity (FVC) (P=0.0427) and more frequently had a FVC under 80 %, when compared to patients with low ATA levels (P=0.0423). Initial high ATA levels were associated with vascular progression at one year (21.95 % vs. 0 %; P=0.0495). CONCLUSION: ATA levels are associated with skin sclerosis and vascular progression in SSc. Beyond the detection of ATA, quantifying this autoantibody might be of interest in predicting disease severity and prognosis in SSc.

[IgG4-related disease: A proteiform pathology with frequent chest manifestations]. / Maladie associée aux IgG4 : une maladie protéiforme aux manifestations thoraciques fréquentes.

INTRODUCTION: While IgG4-related disease (IgG4-RD) was initially described in the early 2000s, its polymorphic clinical manifestations were previously reported under different names ; they have in common the presence of IgG4+ oligoclonal plasma cells and fibrosis. STATE OF THE ART: Ruling out certain differential diagnoses, the diagnosis of IgG4-RD is based on a bundle of clinical, biological and histological features. Chest involvement is variable and can affect the mediastinum, bronchi, parenchyma, pleura and/or, more rarely, bones and (pericardium, aorta, coronary…) vascular structures. The most frequent radiological manifestations are peribronchovascular thickening, mediastinal lymphadenopathy, and nodular or interstitial patterns. Pleural involvement and posterior mediastinal fibrosis are less frequent, while thoracic paravertebral tissue thickening is highly specific. Systemic corticosteroids are the cornerstone of treatment. In case of relapse or as frontline therapy in case of risk factors for relapse and/or poor tolerance of corticosteroids), a steroid-sparing agent (most often rituximab) is added, and biannual maintenance infusions are associated with a lower risk of relapse. PERSPECTIVES: An international consensus has recently led to the development of classification criteria that should standardize the diagnostic approach and homogenize the enrolment of patients in epidemiological as well as therapeutic studies. Other treatments are also under evaluation, including biologics targeting T2 inflammation, CD-19 (inebilizumab, obexelimab), SLAMF7 (elotuzumab) surface proteins, Bruton's tyrosine kinase, and the JAK/STAT pathway. CONCLUSIONS: Substantial progress has been made over recent years in understanding IgG4-RD pathophysiology, and personalized patient care seems to be an achievable medium-term goal.

[Hospitalization for infection in patients treated for giant cell arteritis: A single-centre retrospective study]. / Hospitalisation pour infection chez les patients suivis pour une artérite à cellules géantes : étude monocentrique rétrospective.

INTRODUCTION: Infections are associated with morbimortality of patients with giant cell arteritis (GCA). The aim of this work was twofold: the identification of factors predisposing to the risk of infection and the description of patients hospitalized with an infection occurring during the treatment period of CAG. METHODS: A monocentric retrospective study was conducted in GCA patients, comparing patients hospitalized for infection with patients without infection. The analysis included 21/144 (14.6%) patients with 26 infections (cases) and 42 control matched on sex, age, and diagnosis of GCA. RESULTS: Both groups were similar except for a higher frequency of seritis in cases (15% vs. 0%, p=0.03). Relapses of GCA were less common in cases (23.8% vs 50.0%, p=0.041). Hypogammaglobulinemia was present during infection. More than half of the infections (53.8%) occurred in the first year of follow-up with an average dose of 15mg/day of corticosteroids. Infections were mainly pulmonary (46.2%) and cutaneous (26.9%). CONCLUSION: Factors associated with infectious risk were identified. This preliminary monocentric work will continue with a national multicentre study.

[Anti-cytokine autoantibodies: Review of the literature]. / Anticorps anti-cytokines : quel impact clinique en pathologie humaine ?

Anti-cytokine antibodies (ACA) are an emerging cause of acquired immunodeficiency, especially in previously healthy adults. The most frequently reported are anti-IFN-γ responsible for disseminated non-tuberculous mycobacteria infections, and anti-GM-CSF mainly in mycobacteria, cryptococcosis and nocardiosis infections. The presence of anti-IFN-α in severe COVID-19 infections has recently been described. The search for and detection of these ACAs in an unusual infection situation makes it possible to set up specific therapies in addition to the anti-infective treatment. ACAs are also frequent in various autoimmune pathologies where, in addition to being indicators of the breakdown of immune tolerance, they can modulate the activity of the disease according to their cytokine target. In this review of the literature, we will focus on the epidemiology and the clinical impact of these ACAs in healthy subjects and in infectious or dysimmune diseases.

Approche thérapeutique des maladies de Castleman : l'émergence des thérapies ciblées.

The spectrum of Castleman disease encompasses several different disorders. Nowadays three different forms of the disease are individualized: unicentric Castleman disease, multicentric HHV-8 associated Castleman disease and idiopathic multicentric Castleman disease. In the latter a severe form called TAFRO syndrome (thrombocytopenia, anasarca, myelofibrosis, renal dysfunction, and organomegaly) tend to be individualized. Improvement in the classification and understanding of the physiopathology of CD have allowed improvement in treatment strategies. Treatment of rare but often severe manifestations, such as paraneoplastic pemphigus and bronchiolitis obliterans in unicentric CD and hemophagocytic syndrome and/or Kaposi' sarcoma in HHV8 associated CD, are better adapted. Most of current treatment strategies are based on retrospective and very few prospective studies. Both anti-IL6/6R and anti-CD20 biotherapies have greatly improved the management of certain forms of the disease. We report in this review the most relevant studies and national or international expert consensus statements for the treatment in the different types of CD. © 2022 Published by Elsevier Masson SAS on behalf of Société nationale française de médecine interne (SNFMI).

[Idiopathic systemic capillary leak syndrome: 2 cases with misleading presentation]. / Syndrome de fuite capillaire idiopathique : 2 cas cliniques de présentation trompeuse.

INTRODUCTION: Idiopathic systemic capillary leak syndrome (ISCLS) also known as Clarkson syndrome is a rare and sudden life-threatening entity. Three consecutive phases are described. A first non-specific prodromal phase often manifests as "flu-like" symptoms and precedes capillary leak phase with major hypovolemic and distributive shock leading to serious and frequent multiorgan dysfunction syndrome (MODS). Severe hypovolemia contrasts with edema, and hemoconcentration with hypoalbuminemia. ISCLS is characterized by these two clinical and biological paradoxes. Subsequent recovery phase exhibits organ function restoration along with interstitial/intravascular volumes normalization. The latter occurs spontaneously and systematically in patients surviving from leak phase. OBSERVATIONS: We report here two ISCLS cases admitted in intensive care unit (ICU) both enhancing initial misdiagnosis possibly lowering prognosis and outcome. Our first 28-year-old female patient was admitted for « polycythemia vera ¼ although hemoconcentration was attributable to hypovolemia. She presented circulatory arrest during the second bloodletting session and complicated with MODS. In and out ICU favorable outcome was noted on intravenous immunoglobulin therapy. A second 57-year-old male patient was admitted in ICU for severe "myositis" (myalgia and rhabdomyolysis) although rectified diagnosis retained compartment syndrome (muscular severe edema following capillary leak). Rapid and refractory hypovolemic shock appeared with subsequent MODS leading to death. CONCLUSION: ISCLS pathophysiology remains unknown but certainly implies transitory endothelial dysfunction. Impossibility of randomized controlled trial for this exceptional disease led to based-on-experience therapeutic guidelines implying symptomatic care (cardiac output surveillance, nephroprotection, prudent fluid intake, prudent vasoactive amine use) and specific therapies (intravenous aminophylline during severe flares). Although enhancing controversial and even deleterious effects during the acute phase, polyvalent immunoglobulins are effective for relapse prevention. Syndromic diagnosis is difficult, but its precocious finding constitutes a key-element in better outcome before organ failure.

[Expectation of patients and caregivers about patient education for immune thrombocytopenia]. / Attentes en éducation thérapeutique des patients atteints de purpura thrombopénique immunologique et des soignants.

INTRODUCTION: Immune thrombocytopenia (ITP) durably affects quality of life in patients. Patient education aims at improving their self-care and psychosocial skills, allowing them be more autonomous, to prevent avoidable complications, and to maintain or improve quality of life. The aim of this study was to assess patients' and caregivers' expectations regarding patient education in ITP. METHOD: ITP Patients and caregivers were asked about topics that should be addressed in a patient education program through a digital anonymous survey. Their responses were analyzed both qualitatively and quantitatively. A double-blind keyword attribution of the answers was carried out by two physicians and then faced until consensus was found. RESULTS: Thirty-eight ITP patients were included: 68% were less than 50 years old and 84% had chronic ITP. On the other hand, twenty-five caregivers were included. Caregivers raised more topics related to the cognitive domain than patients. The psychoaffective and motivational topics tended to be more represented in patients' responses. Only 53% of topics were mentioned by both patients and caregivers. CONCLUSION: These discrepancies emphasize the differences between patients and caregivers' expectations regarding a patient education program in ITP, and thus the relevance of patient-caregiver co-construction of such programs.

[IgG4-related disease: Diagnostic criteria evolution toward the 2019 ACR/EULAR classification criteria]. / Maladie associée aux IgG4 : des critères « diagnostiques ¼ aux critères de classification ACR/EULAR 2019.

The concept of IgG4-related disease (IgG4-RD) has recently been individualized in the early 2000s, but most of the organ involvements are known since more than 100 years. IgG4-RD is a non-malignant fibroinflammatory disorder, characterized by peculiar immunological and pathological abnormalities, which can affect virtually all organs or tissues. Diagnostic criteria have been proposed and have evolved rapidly, with general or organ specific criteria. An international and multidisciplinary group assembled by the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) has recently developed and validated a set of classification criteria called 2019 ACR/EULAR classification criteria for IgG4-related disease. The objective of this review is to discuss the evolution from organ specific and general diagnostic criteria toward the 2019 ACR/EULAR classification criteria, as well as respective benefits and limits of these criteria. The use of the 2019 ACR/EULAR classification criteria will help to better define homogeneous group of IgG4-RD patients in future clinical, epidemiological and basic science research studies on the disease.

IgG4 hypophysitis: Diagnosis and management.

IgG4-related hypophysitis is a rare disease, due to a lymphoplasmocytic IgG4 positive infiltration of the pituitary. Literature data are scarce, even though the description of cases has drastically increased over the last years. The aim of this review is to better characterize the natural history, the diagnosis and the management of IgG4-related hypophysitis, based on a clinical case, an exhaustive Pubmed research, and a reappraisal of the criteria for diagnosis. We will specifically focus on the differences with other etiologies of hypophysitis, in the aim of improving the diagnostic procedures for all the physicians who could have to take care of such patients.

[Ocular syphilis, a re-emergent pathology: Series of 12 patients in one Hospital, 2017]. / La syphilis oculaire, une pathologie ré-émergente : série de 12 patients au CHU de Marseille en 2017.

INTRODUCTION: Syphilis is a sexually transmitted disease. All organs might be affected, but ocular syphilis only occurs in 0.6 percent of patients. We collected all cases of ocular syphilis requiring hospitalization at the University Hospital Center (UHC) in Marseille in 2017. PATIENTS AND METHODS: This was a retrospective monocentric study. The diagnosis of ocular syphilis was based on the combination of ocular inflammation with a positive syphilitic serology. For each patient, sex, age, HIV status, ocular and extraocular symptoms, initial visual acuity, syphilis serology, cerebrospinal fluid (CSF) analysis if done, treatment and clinical response were collected. RESULTS: Ten men and two women, aged 28 to 86 years, were hospitalized. Two patients were HIV-positive. Ophtalmological lesions were heterogeneous the posterior structures were most affected. Anterior uveitis was isolated in one patient. Five patients had extraocular signs with cutaneous and/or mucosal involvement. No patient had neurological symptoms. Diagnosis of neurosyphilis through CSF analysis was definite for one patient, probable for 5 patients and ruled out for 2 patients. Six patients received treatment with penicillin G and six with ceftriaxone. Visual acuity improved in all cases. DISCUSSION: Ophtalmic cases of syphilis have become more frequent over the past few years in France. The diagnosis should be suspected in cases of eye inflammation even in the absence of favourable clinical presentation or anamnesis. Search for HIV co-infection should be systematic. Our study shows that ceftriaxone remains an effective alternative to penicillin G.

[Bilateral adrenal hemorrhage under apixaban in primary antiphospholipid syndrome]. / Nécrose hémorragique bilatérale des surrénales sous apixaban : penser au syndrome des antiphospholipides ?

INTRODUCTION: Adrenal hemorrhage is a classical but rare complication of antiphospholipid syndrome, revealing diagnosis in one third of the cases. Anti-vitamin K therapy is the standard treatment but direct oral anticoagulants are discussed as an alternative. In the latest recommendations, it is advised not to use direct oral anticoagulants in the setting of antiphospholipid syndrome. CASE REPORT: We present a case of bilateral adrenal hemorrhage revealing primary antiphospholipid syndrome with triple positive antibody profile, in a 47-year-old man treated by apixaban for previous venous thromboembolism. CONCLUSION: To our knowledge, it is the first case of adrenal hemorrhage occurring during apixaban treatment in a patient with antiphospholipid syndrome. This case illustrates the inefficacy of direct oral anticoagulants to prevent thrombotic events in antiphospholipid syndrome, in accordance with the latest recommendations.

[Systemic sclerosis and macrovascular involvement: Status of the issue in 2019]. / Atteintes macrovasculaires de la sclérodermie : état de la question en 2019.

Systemic sclerosis (SSc) is a rare immune disease leading to fibrosis of the skin and internal organs. Microvasculopathy is a hallmark of SSc. However, some patients have severe macrovascular complications as affecting cerebral, cardiac or peripheral vessels. To date, macrovascular involvement in SSc remains a matter of debate. Many studies have shown an increased prevalence of macrovascular involvement in SSc in comparison with controlled subjects with similar cardiovascular risk factors. Various methods were used: ankle brachial pressure index, intima media thickness, imagery, coronary calcium score, pulse wave velocity, or flow mediated dilation. The pathophysiology of macrovascular involvement remains unknown and is probably multifactorial: accelerated atherosclerosis, endothelial dysfunction, or reflected wave of microvessel obliteration. The aim of this study was to perform a comprehensible review of the literature, through the study of different types of involved vessels. Results of the main studies are summarized in tables according to the method of investigation used.

[Lysozyme amyloidosis]. / L'amylose à lysozyme.

Lysozyme amyloidosis is a non-neuropathic hereditary amyloidosis identified in 1993. About fifty cases of this rare, probably under-diagnosed disease are reported. Lysozyme amyloidosis has a very broad spectrum of clinical manifestations. Sicca syndrome is often the first symptom, preceding the diagnosis by several years. Every part of the digestive tract can be involved with different grades of severity. The hallmark of this amyloidosis is the usually life-threatening spontaneous hepatic rupture. Renal involvement is frequent and progresses towards end-stage renal failure and dialysis. Skin, lymph nodes, and spleen can also be affected. More recently, cardiac and pulmonary involvement was reported. Phenotypic heterogeneity and incomplete penetrance make the clinical diagnosis difficult. Amyloid deposits are revealed by Congo red staining with birefringence under polarized light. They can be limited or diffuse and lead to the progressive destruction of the architecture of an organ and its failure. Immunohistochemistry reveals the nature of the amyloid variant by identifying antilysozyme antibodies in the deposit. Up to know, eight pathologic mutations and one polymorphism involving exons 2, 3, and 4 of the lysozyme gene have been identified. The transmission is autosomal dominant, without any genotype-phenotype correlation. The therapeutic options are limited and based on symptomatic or supportive treatment. Renal and hepatic transplant has proved its benefits with a prolonged graft survival. A long term regular and multidisciplinary follow-up is required.

[Characteristics of giant cell arteritis patients under and over 75-years-old: A comparative study on 164 patients]. / Caractéristiques des patients de moins et de plus de 75 ans atteints d'artérite à cellules géantes : étude comparative de 164 patients.

PURPOSE: Giant cell arteritis (GCA) is the most common vasculitis of the elderly. In order to assess the impact of age at diagnosis, we compared the characteristics of patients of less than 75 years (<75 years), to those of the 75 years and over (≥75 years). PATIENTS AND METHODS: We conducted a retrospective study on 164 patients with GCA diagnosed from 2005 to 2017. All patients had at least 3/5 of the ACR criteria and had a CT-scan at diagnosis. The mean age was of 73±9.6 years. The age was<75 years for 84 patients (59 women) and≥75 years for 80 patients (53 women). RESULTS: Patients≥75 years had more cardiovascular underlying diseases (P=0.026), a higher rate of hypertension (P=0.005) and more ophthalmic complications (P=0.02). They had less large vessel involvement (P<0.001), showed lower biological inflammatory reaction and had a more frequently positive temporal artery histology (P=0.04). The oral initial dose of corticosteroids did not differ between the groups. Corticosteroids pulse therapy was more frequent in patients≥75 years (P=0.01). The frequency of anti-platelet agents use was similar in the two groups. Relapse rate, corticodependance and the rate of corticosteroids weaning were similar in both groups. CONCLUSION: Patients≥75 years at diagnosis of GCA were at lower risk of aortitis but were more likely to suffer from ophthalmic complications and to receive corticosteroid pulse therapy.