[Severe small bowel involvement and chronic intestinal pseudo-obstruction in systemic sclerosis (scleroderma): Pathophysiological, diagnostic and therapeutic basis, including parenteral nutrition]. / Atteinte sévère de l'intestin grêle et pseudo-obstruction intestinale chronique au cours de la sclérodermie systémique : bases physiopathologiques, diagnostiques et thérapeutiques, dont la nutrition parentérale.

Gastrointestinal involvement in systemic sclerosis can be severe, reaching the critical point of chronic intestinal pseudo-obstruction, secondary to major disorders of small bowel motility. It is associated with some clinical and biological characteristics, in particular the positivity of anti-fibrillarin/U3RNP antibodies. Chronic intestinal pseudo-obstruction (CIPO) is complicated by a small intestinal bacterial overgrowth that requires cyclic antibiotic therapy. CIPO leads to a reduction of the food intake, due to painful symptoms, nausea and vomiting caused by meals, and ultimately to severe malnutrition. Meal splitting is often transiently effective and patients require exogenous nutritional support, mostly parenteral. Systemic sclerosis is not an obstacle to initiation and long-term continuation of parenteral nutrition and central venous catheter implantation is not associated with an increased risk of cutaneous or infectious complications. However, continuation of long-term parenteral nutrition requires monitoring in an expert nutrition center in order to adapt nutritional volumes and intakes and to limit potentially fatal cardiac and hepatobiliary complications. In addition to nutrition, prokinetic treatments, whose side effects must be known, can be associated. Invasive procedures, whose risk-benefit ratio must be carefully assessed, can also be used to treat symptoms exclusively.

[Infections in primary Sjögren's syndrome patients: "Real-life" study of 109 patients from Montpellier university hospital]. / Infections rapportées chez 109 patients avec syndrome de Gougerot-Sjögren primaire suivis au CHU de Montpellier.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Further characterization of clinical and laboratory features in VEXAS syndrome: large-scale analysis of a multicentre case series of 116 French patients.

BACKGROUND: A new autoinflammatory syndrome related to somatic mutations of UBA1 was recently described and called VEXAS syndrome ('Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome'). OBJECTIVES: To describe clinical characteristics, laboratory findings and outcomes of VEXAS syndrome. METHODS: One hundred and sixteen patients with VEXAS syndrome were referred to a French multicentre registry between November 2020 and May 2021. The frequency and median of parameters and vital status, from diagnosis to the end of the follow-up, were recorded. RESULTS: The main clinical features of VEXAS syndrome were found to be skin lesions (83%), noninfectious fever (64%), weight loss (62%), lung involvement (50%), ocular symptoms (39%), relapsing chondritis (36%), venous thrombosis (35%), lymph nodes (34%) and arthralgia (27%). Haematological disease was present in 58 cases (50%): myelodysplastic syndrome (MDS; n = 58) and monoclonal gammopathy of unknown significance (n = 12; all patients with MGUS also have a MDS). UBA1 mutations included p.M41T (45%), p.M41V (30%), p.M41L (18%) and splice mutations (7%). After a median follow-up of 3 years, 18 patients died (15·5%; nine of infection and three due to MDS progression). Unsupervised analysis identified three clusters: cluster 1 (47%; mild-to-moderate disease); cluster 2 (16%; underlying MDS and higher mortality rates); and cluster 3 (37%; constitutional manifestations, higher C-reactive protein levels and less frequent chondritis). The 5-year probability of survival was 84·2% in cluster 1, 50·5% in cluster 2 and 89·6% in cluster 3. The UBA1 p.Met41Leu mutation was associated with a better prognosis. CONCLUSIONS: VEXAS syndrome has a large spectrum of organ manifestations and shows different clinical and prognostic profiles. It also raises a potential impact of the identified UBA1 mutation.

Evaluation of Clinical Trials in Onco-haematology: A New Method Based on Risk Analysis and Multidisciplinarity.

BACKGROUND: European member states are increasingly vying with one another to recruit patients for clinical trials (CTs). The French national agency for medicines (ANSM) now receives an ever-growing number of CTs, extending response times. The aim of the new methodology presented herein is to reduce assessment times below the national mandatory timeframe of 60 days and to improve patient safety. MATERIALS AND METHODS: Based on an analysis of the criteria defining CTs, 4 key points were identified (safety, fragile population, loss of opportunity, design complexity) to build a criticality score which would determine evaluation type. This score also determines the resources needed (complete evaluation, multidisciplinary advice, ad hoc evaluation) and the timeframe required for appropriate analysis. All post-phase I CTs were analysed from the implementation of the new assessment method, on 01/02/2018 through to 31/12/2019. RESULTS: 447 CTs were analysed (63% industry and 37% academic sponsors). Based on a criticality scale, 27% of the CTs received a type A evaluation (complete), 37% a type B (multidisciplinary evaluation), 23% a type C evaluation (ad hoc evaluation) and 13% a type D evaluation (fast evaluation). From 2014 to 2017, 37% of the CTs were analysed within the mandatory timeframe, with a mean of 68 days, reaching a maximum of 102 days in 2017. Using this new assessment method, 92% of CTs respected the mandatory timeframe in 2019; the mean time in 2018-2019 was 34 days; Grounds for Non-Acceptance (GNA) were raised for 66% of the CTs (69% from academic sponsors and 65% from industrial firms). 3 CTs were refused. CONCLUSION: Here, we demonstrate the feasibility of risk analysis and multidisciplinarity method, which resulted in a dramatic improvement of assessment times.

[Thrombotic thrombocytopenia purpura in Martinique: Retrospective study between 2008 and 2015]. / Le purpura thrombotique thrombocytopénique à la Martinique : étude rétrospective entre 2008 et 2015.

INTRODUCTION: Some studies suggest that thrombotic thrombocytopenic purpura (TTP) occurs more often in African Americans. However there is low evidence for this in the literature. The aim of our study was to describe the clinical and biological characteristics of TTP in the Afro-Caribbean population of Martinique. METHODS: We retrospectively analysed all patients with TTP diagnosed at the Fort-de-France hospital between 2008, January 1st and 2015, December 31st. Diagnosis was confirmed if ADAMTS-13 activity was<10 %. RESULTS: Ten patients were included, corresponding to an average annual incidence of 3.2 cases/year/million individuals. None of the patient presented with the association of the five characteristic features of TTP. Microangiopathic haemolytic anaemia and severe peripheral thrombocytopenia (median: 13G/L) was the main presentation leading to diagnosis. There was no kidney involvement in 90 % of all patients, but severe neurological manifestations occurred in 70 %. Classical management including corticosteroids and plasma exchanges allowed clinical remission in 6 out of the 10 cases. If necessary, rituximab or cyclophosphamide was used. The overall survival rate was 90 %. CONCLUSION: In Martinique, the incidence of TTP is twice that reported in similar studies in France. Clinical manifestations seem to differ by more common and more severe neurological involvement. Mortality is low, in part, due to optimal care.

[Well's cellulitis: A case report]. / La cellulite de Wells : à propos d'une observation.

INTRODUCTION: Wells's cellulitis is a rare eosinophilic dermatose characterized by an inflammatory erythematous eruption, often associated with eosinophilia, and suggestive histologic features. The differential diagnosis with other eosinophilic dermatitis is problematic. The treatment is typically based on systemic steroids. CASE REPORT: We report a 63-year-old patient with an extensive pruritic maculo-papular eruption of the limbs and the trunk, forming large indurated and painful erythematous patches. Blood analysis revealed eosinophilia. Histologic examination showed perivascular eosinophilic inflammatory infiltration, also disposed around collagen fibers. The symptoms disappeared with topical corticosteroids. CONCLUSION: The diagnosis of Well's cellulitis is difficult because of the lack of specific sign; it is based on suggestive clinical, biological and histological features. Topical corticosteroids are efficient and well-tolerated, and should be used as first treatment.

[Clustered cases of histoplasmosis due to Histoplasma capsulatum var. capsulatum in Martinique: Case reports and environmental investigation]. / Cas groupés d'histoplasmoses à Histoplasma capsulatum var. capsulatum à la Martinique : description des cas et enquête environnementale.

Between the 24th of June and the 6th of July 2005, nine men came to Fort-de-France emergency department (Martinique, French West Indies) with more or less pronounced pulmonary symptoms associated in two cases with skin lesions. Three weeks before these nine men performed work in a deserted house. The diagnosis of histoplasmosis was based on pulmonary sample mycological analysis (direct examination and culture), molecular biology and serological tests. Interrogatory and environmental investigations on the presumed place of exposition to H. capsulatum var. capsulatum spores allowed confirming how and where contamination took place.

[Pyoderma gangrenosum and neutrophilic aortitis preceding the development of rheumatoid arthritis]. / Pyoderma gangrenosum et aortite neutrophilique précédant l'apparition d'une polyarthrite rhumatoïde.

BACKGROUND: We report a case of pyoderma gangrenosum (PG) associated with a complication comprising ascending aortic dissection (neutrophilic aortitis) in a setting of rheumatoid arthritis (RA). PATIENTS AND METHODS: A 79-year-old female patient was hospitalized in late 2009 for vegetating PG. Treatment with general steroids followed by colchicine and topical steroids resulted in complete healing of skin lesions. During hospitalization, the patient presented dissection of the ascending part of the aorta, for which emergency surgery proved effective. Histological examination of the excised tissue revealed diffuse neutrophilic aortitis. Diagnoses of Takayashu's disease and of lupus were ruled out. A chest CT scan showed interstitial lung disease with mild lymphocytosis in the bronchoalveolar fluid, but with no isolated pathogenic organisms. Relapse of skin lesions occurred 3 and 4 years later, associated with the development of RA, and worsening of the interstitial lung disease was noted in a scan carried out it in 2013, following which stabilization was observed in April 2014. There was no recurrence of the PG lesions. CONCLUSION: To our knowledge, no other cases involving association of neutrophilic aortitis with PG and RA has been published to date. The literature describes the emergence of the concept of systemic neutrophilic dermatoses, and this notion is reinforced by the presence of a cutaneous and aortic site of the neutrophilic disease in a single patient.

[Cost of systemic lupus erythematosus for adult patients with active and treated disease in France (LUCIE study)]. / Coût du lupus systémique en France des patients adultes avec une maladie active et traitée (étude LUCIE).

PURPOSE: To evaluate in France the annual direct medical cost of adult patients with active systemic lupus erythematosus (SLE) on medication and estimate the cost of a flare. METHODS: A two-year, observational, retrospective, multicenter study, carried out between December 2010 and February 2011. Patients' characteristics, SLE disease activity and severity, rate of flares, healthcare consumption (medications, hospitalisations, etc.) were evaluated. Medical costs were assessed from the national Health Insurance perspective. Cost predictors were estimated using multivariate regression models. RESULTS: Eight centres specialized in SLE management included 93 eligible patients (including 50.5% severe). The mean age was 39.9 (11.9) years and 93.5% were women. At baseline, the mean SLE duration was 9.8 (6.6) years. The mean scores of the SELENA-SLEDAI instrument and the SLICC/ACR index were higher in severe patients (9.8 vs 5.6, and 1.2 vs 0.4 respectively; P<0.001). Over the study period, 51% of patients received the combination containing at least corticosteroids or immunosuppressants. The mean annual direct medical cost of severe patients was €4660 versus €3560 for non-severe patients (non-significant difference). The cost of medications (61.8% of the annual cost) was higher in severe patients (€3214 vs €1856; P<0.05). Immunosuppressants and biologics represented 26.5% and 4.6% of the annual total cost respectively. Patients experienced on average 1.10 (0.59) flares/year, of which 0.50 were severe flare. The occurrence of a new severe flare incremented the annual cost of €1330 (P<0.05). CONCLUSION: Medications represented the major component of the annual direct medical cost. Severe flares increase significantly the cost of SLE care management.

Pure cutaneous lupus erythematosus in a population of African descent in French Guiana: a retrospective population-based description.

The objective of this study was to examine the characteristics of cutaneous lupus erythematosus, excluding systemic lupus erythematosus (SLE), in patients of African descent. Indeed, since the description of subacute cutaneous lupus erythematosus (SCLE), which had been included in chronic cutaneous lupus erythematosus (CCLE), there has been no description of the disease in black patients. In 2000, we performed a retrospective epidemiological study by querying multiple sources to identify all patients with lupus in French Guiana--a part of France in South America having western living conditions, free healthcare and 157,000 inhabitants, most of whom are of African origin. We found 45 patients with pure cutaneous lupus, which included CCLE (mostly discoid), SCLE and bullous lupus. The disease characteristics of these patients exhibited few differences compared with those of the Caucasian patients cited in the literature. However, the age of onset for our patients of African descent was younger than that of Caucasian patients. In contrast to the race-related differences reported for SLE, we found no major differences in terms of demographic, clinical and biological presentation between this cohort of pure cutaneous lupus erythematosus patients of African origin and Caucasian patients with similar forms of lupus.

Lytic bone lesions in lupus-associated myelofibrosis.

Myelofibrosis is associated with numerous causes other than hematologic malignant neoplasms, including autoimmune diseases. We describe a 44-year-old woman who suffered bone lytic lesions with extramedullary haematopoiesis in the setting of myelofibrosis associated with systemic lupus erythematosus.

Is African descent an independent risk factor of peripartum cardiomyopathy?

Risk factors for peripartum cardiomyopathy (PPCM) are controversial. PPCM seems to be more prevalent in women of African descent, the highest observed incidence is in Haiti (1 per 300 live births). Our retrospective study conducted in Martinique showed an incidence of 1 per 5500 live births. This incidence is significantly lower than in Haiti. Women from Martinique and Haiti do not differ for most classical risk factors: African descent, age, pregnancy-associated hypertension, multiple pregnancy and pre-eclampsia. However, the parity rate and the socioeconomic level are different. Thus, African descent could be confounded by high parity rate and socioeconomic status.

[Diabetic muscular necrosis: three Afrocaribbean cases]. / Nécrose musculaire du diabétique : trois cas Afro-caribéens.

INTRODUCTION: Diabetic muscular infarction is an exceptional complication of diabetes mellitus. Patients with macro- and microvascular manifestations are mostly concerned. Muscular pain with swelling of the thigh is the main manifestation, sometimes associated with fever. OBSERVATIONS: We report here five cases of diabetic muscular infarction in three Afro-carribean patients with atypical clinical features. The surgical biopsy procedure allowed the diagnosis and ruled out pyomyositis, a more common bacterial disease on tropical condition. CONCLUSION: This report of three cases of this exceptional disease in a small population seems more related to the high prevalence of diabetes mellitus in the French West Indies than to their ethnic origin.