Bone marrow involvement in systemic lupus erythematosus.

BACKGROUND: Besides peripheral cytopenias, bone marrow abnormalities, such as fibrosis, pure red cell aplasia and aplastic anemia have been reported in patients with systemic lupus erythematosus (SLE), suggesting that bone marrow may be a 25 target organ in SLE. AIM: Our objective was to describe this bone marrow involvement. METHODS: This registry is a nationwide retrospective study. Centers provided data concerning medical history, SLE manifestations, type of hematologic disorder, treatments and outcome. Bone marrow aspirations and/or biopsies were transferred for centralized review. RESULTS: Thirty patients from 19 centers were included. Central hematologic manifestations comprised bone marrow fibrosis (n = 17; 57%), pure red cell aplasia (n = 8; 27%), myelodysplastic syndrome (n = 3; 10%), aplastic anemia and agranulocytosis (n = 1; 3% each). Bone marrow involvement was diagnosed concomitantly with SLE in 12 patients. Bone marrow biopsies showed fibrosis in 19 cases, including one case of pure red cell aplasia and one case of agranulocytosis and variable global marrow cellularity. Treatments included corticosteroids (90%), hydroxychloroquine (87%), rituximab (33%), intravenous immunoglobulins (30%), mycophenolate mofetil (20%) and ciclosporine (20%). After a median follow-up of 27 months (range: 1-142), 24 patients manifested complete improvement. No patient died. CONCLUSIONS: This registry comprises the largest series of SLE patients with bone marrow involvement. It demonstrates the strong link between SLE and bone marrow fibrosis. Patients with atypical or refractory cytopenia associated with SLE should undergo bone marrow examination to enable appropriate, and often effective, treatment. Long-term prognosis is good.

Personalized thromboprophylaxis using a risk score for the management of pregnancies with high risk of thrombosis: a prospective clinical study.

Essentials Pregnancy is a risk factor for thrombosis. Management of thrombosis risk in pregnancy remains a challenge. Prophylaxis needs to be personalized. Our score may be a helpful tool for the management of pregnancies at high risk of thrombosis. SUMMARY: Background Patients with thrombophilia and/or a history of venous thromboembolism (VTE) are at risk of thrombosis during pregnancy. A risk score for pregnancies with an increased risk of VTE was previously described by our group (Lyon VTE score). Objectives The aim of this prospective study was to assess the efficacy and safety of our score-based prophylaxis strategy in 542 pregnancies managed between 2005 and 2015 in Lyon University Hospitals. Patients/Methods Of 445 patients included in the study, 36 had several pregnancies during the study period. Among these 445 patients, 279 had a personal history of VTE (62.7%), 299 patients (67.2%) had a thrombophilia marker, and 131 (29.4%) thrombophilic women had a personal history of VTE. During pregnancy, patients were assigned to one of three prophylaxis strategies according to the risk scoring system. Results In the antepartum period, low molecular weight heparin (LMWH) prophylaxis was prescribed to 64.5% of patients at high risk of VTE. Among them, 34.4% were treated in the third trimester only, and 30.1% were treated throughout pregnancy. During the postpartum period, all patients received LMWH for at least 6 weeks. Two antepartum-related VTEs (0.37%; one with a score of < 3 and the other with a score of > 6) and four postpartum-related VTEs (0.73%; three with scores of 3-5 and one with a score of > 6) occurred. No case of pulmonary embolism was observed during the study period. The rate of bleeding was 0.37%. No serious bleeding requiring transfusions or surgery occurred during the study period. Conclusion The use of a risk score may provide a rational decision process to implement safe and effective antepartum thromboprophylaxis in pregnant women at high risk of VTE.

The Clinical Relevance of Antifibrillarin (anti-U3-RNP) Autoantibodies in Systemic Sclerosis.

Systemic sclerosis (SSc) is a heterogeneous autoimmune disease associated with several antinuclear autoantibodies useful to diagnosis and prognosis. The aim of the present multicentric study was to determine the clinical relevance of antifibrillarin autoantibodies (AFA) in patients with SSc. The clinical features of 37 patients with SSc positive for AFA (AFA+) and 139 SSc patients without AFA (AFA-) were collected retrospectively from medical records to enable a comparison between AFA- and AFA+ patients. Antifibrillarin autoantibodies were screened by an indirect immunofluorescence technique using HEp2 cells and identified by an in-house Western blot technique and/or an EliA test. Comparing AFA+ and AFA- patients, AFA+ patients were significantly younger at disease onset (36.9 versus 42.9; P = 0.02), more frequently male (P = 0.02) and of Afro-Caribbean descent (65% versus 7.7%; P < 0.001). At diagnosis, the Rodnan skin score evaluating the cutaneous manifestations was higher (13.3 versus 8.7; P = 0.01) and myositis was also more common in the AFA+ group (31.4% versus 12.2%; P < 0.01). Patients with AFA+ were not associated with diffuse cutaneous SSc or with lung involvement and no difference in survival was observed. Antifibrillarin autoantibodies are associated with patients of Afro-Caribbean origin and can identify patients with SSc who are younger at disease onset and display a higher prevalence of myositis.

[Prevention of infections in adults and adolescents with systemic lupus erythematosus: Guidelines for the clinical practice based on the literature and expert opinion]. / Prévention des infections au cours du lupus systémique chez l'adulte et l'adolescent : élaboration de recommandations pour la pratique clinique, à partir d'une analyse de la littérature et de l'avis d'experts.

PURPOSE: To develop French recommendations about the management of vaccinations, the screening of cervical cancer and the prevention of pneumocystis pneumonia in systemic lupus erythematosus (SLE). METHODS: Thirty-seven experts qualified in internal medicine, rheumatology, dermatology, nephrology and pediatrics have selected recommendations from a list of proposition based on available data from the literature. For each recommendation, the level of evidence and the level of agreement among the experts were specified. RESULTS: Inactivated vaccines do not cause significant harm in SLE patients. Experts recommend that lupus patient should receive vaccinations accordingly to the recommendations and the schedules for the general public. Pneumococcal vaccination is recommended for all SLE patients. Influenza vaccination is recommended for immunosuppressed SLE patients. Live attenuated vaccines should be avoided in immunosuppressed patients. Yet, recent works suggest that they can be considered in mildly immunosuppressed patients. Experts have recommended a cervical cytology every year for immunosuppressed patients. No consensus was obtained for the prevention of pneumocystis pneumonia. CONCLUSION: These recommendations can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of SLE patients.

[Association of lymphoma and granulomatosis: A case series]. / Association lymphome et granulomatose : à propos d'une série de cas.

PURPOSE: The sarcoidosis-lymphoma syndrome is a recognised entity. However, the presence of granulomas in patients with a haematological disease should not lead too easily to a diagnosis of sarcoidosis. The presence of granulomatous lesions during the follow-up of these patients raises diagnostic and therapeutic issues. METHODS: We included 25 patients followed by the department of haematology in a French hospital (Centre Léon-Bérard). These patients presented with granulomatous lesions. Patients with a history of sarcoidosis were excluded. We report the type of haematological disease, the time of onset of the granulomatous disease compared to that of lymphoma, associated symptoms, aetiology and outcome. Patients were divided into three groups according to the time of onset of the granulomatous lesions. RESULTS: Granulomatous lesions appeared before the haematological disease in 4 cases, was concomitant in 8 cases and appeared later in 13 remaining cases. The two main subtypes of lymphoma encountered were: diffuse large cell lymphoma (36%) and Hodgkin's lymphoma (28%). Granulomatous lesions were related to the progression of the hematological disease in 11 cases, to sarcoidosis in 4 cases, to infection in 3 cases, to drug allergy in one case, to inflammatory bowel disease in one case, to granuloma annulare in one case and was isolated in 4 cases (no identified etiology). In the group where granulomas appeared after the haematological disease, mean SUV was 11 for the haematological disease versus 6.4 for granulomas. CONCLUSION: Granulomatous diseases in lymphomas can be due to various aetiologies: infection, reaction to the haematological disease, or systemic sarcoidosis. It is an important challenge for clinicians, who can miss the diagnosis of lymphoma and or conclude to a treatment failure or a relapse. Computed tomography scan (CT-scan) or (18)F-deoxyglucose-positron emission tomography scan can help establish a diagnosis but do not replace biopsy.

Impairment of quality of life in patients with antiphospholipid syndrome.

OBJECTIVES: Health-related quality of life (HRQoL) has not been fully explored in antiphospholipid syndrome (APS); therefore, we compared HRQoL between APS patients and the general population and assessed the impact of thromboembolic history. METHODS: HRQoL was measured in a multicentre cohort study by the Medical Outcomes Study Short-Form 36 (MOS-SF-36) questionnaire. HRQoL scores were compared to the French general population norms. Factors significantly associated with an impaired HRQoL were identified. RESULTS: A total of 115 patients with aPL and/or systemic lupus erythematosus (SLE) were included (mean age 42.7 ± 14.1 years old, 86 women). In 53 patients APS was diagnosed. Compared to general population norms, patients with APS had an impaired HRQoL. SLE-associated APS patients had the worst HRQoL scores (physical component summary (PCS)=40.8 ± 10.6; mental component summary (MCS)=40.6 ± 16.5) in comparison with SLE or aPL patients without thromboembolic history. In APS patients, history of arterial thrombosis significantly impaired HRQoL (PCS score: 42.2 ± 9.4 vs 49.2 ± 8.5; MCS score: 33.9 ± 13.7 vs 44.6 ± 10.3). CONCLUSION: Compared to the general population, APS patients experienced a lower HRQoL. In these patients, a history of arterial thrombosis significantly impaired HRQoL. Therefore, measurements of HRQoL should be included in APS patient management to assess the burden of the disease from a patient's perspective and to provide patients with the support they need.

[An unusual case of duodenal sarcoidosis]. / Sarcoïdose duodénale: à propos d'un cas.

INTRODUCTION: Sarcoidosis is a systemic granulomatous disorder of unknown aetiology. It may rarely affect the gastrointestinal tract. CASE REPORT: We reported a 54-year-old woman with a delayed diagnosis of duodenal sarcoidosis. She presented with gastric and right upper abdominal pain associated with vomiting and marked weight loss. Abdominal computed tomographic scan showed non-compressive retroperitoneal lymph nodes and histological examination revealed non-caseating epithelioid granulomas typical of sarcoidosis. Diagnosis of duodenal sarcoidosis was obtained at the third gastroscopy. The patient's condition improved quickly with corticosteroid therapy. CONCLUSION: Gastrointestinal sarcoidosis should be looked for in patients with digestive symptoms and another sarcoid localisation. Furthermore, it is important to repeat gastroscopy to confirm diagnosis because treatment improved most patients.

[Screening and management of cardiovascular risk factors in systemic lupus erythematosus: Recommendations for clinical practice based on the literature and expert opinion]. / Dépistage et prise en charge du risque cardiovasculaire au cours du lupus systémique : élaboration de recommandations pour la pratique clinique, à partir d'une analyse de la littérature et de l'avis d'experts.

PURPOSE: To develop French recommendations about screening and management of cardiovascular risk factors in systemic lupus erythematosus (SLE). METHODS: Thirty-nine experts qualified in internal medicine, rheumatology and nephrology have selected recommendations from a list developed based on evidence from the literature. For each recommendation, the level of evidence and the level of agreement among the experts were specified. RESULTS: Experts recommended an annual screening of cardiovascular risk factors in SLE. Statins should be prescribed for primary prevention in SLE patients based on the level of LDL-cholesterol and the number of cardiovascular risk factors, considering SLE as an additional risk factor. For secondary prevention, experts have agreed on an LDL-cholesterol target of <0.7 g/L. Hypertension should be managed according to the 2013 European guidelines, using renin-angiotensin system blockers as first line agents in case of renal involvement. Aspirin can be prescribed in patients with high cardiovascular risk or with antiphospholipid antibodies. CONCLUSION: These recommendations about the screening and management of cardiovascular risk factors in SLE can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of SLE patients.

[Auto-immune diseases and cancers. Second part: auto-immune diseases complicating cancers and their treatment]. / Maladies auto-immunes et cancers. Deuxième partie: maladies auto-immunes au cours des cancers et de leur traitement.

Autoimmune diseases may reveal or occur during the course of a neoplasia or its treatment. Autoimmune cytopenia, especially haemolytic anaemia, is common in lymphoproliferative disorders such as chronic lymphoid leukemia. The link between cancer and myositis is well established. Dermatomyositis is associated with an increased relative risk of cancer of 3.4 to 4.4. A combination of detection of antibodies against p155 and TEP-computed tomography may be the best approach to ascertain the presence of occult malignancy in patients with dermatomyositis. A cutaneous or a systemic vascularitis may reveal a cancer, most often a haematological malignancy such as hairy cell leukemia. Paraneoplastic polyarthritis have been described in particular with adenocardinoma of the lungs. Underlying neoplasia should be considered in male smokers patients with new onset polyarthritis and poor health status. The prevalence of autoimmune conditions in myelodysplastic syndromes is 10 to 30%. Vasculitis and relapsing polychondritis are the most commonly reported manifestations. Immune manifestations can also be related to treatment. The most common treatment complications are autoimmune haemolytic anaemia with fludarabine and thyroiditis related to interferon and cervical radiotherapy.

[Infectious thoracic aortic aneurysms: 7 cases and literature review]. / Anévrismes infectieux de l'aorte thoracique : présentation de 7 cas et revue de la littérature.

PURPOSE: Infectious aortic aneurysms are rare conditions, being responsible of 2% of aortic aneurysms. Most published results are surgical case series concerning infected abdominal aorta. In this retrospective study, we assessed clinical features and outcome of patients presenting infectious thoracic aortic aneurysms. PATIENTS AND METHODS: Diagnosis was based upon a combination of imaging evidence for thoracic aorta aneurysm and evidence for an infective aetiology including a culture of a causative pathogen, or a favourable outcome with anti-infective therapy. Retrospective case series. RESULTS: Six men and one woman were included, with a mean age of 66 years. All the patient presented at least one cardiovascular risk factor or atherosclerosis localisation. Fever (71%) and chest pain (42%) were the most common clinical presenting manifestations. The causative pathogens were: Staphylococcus aureus (N=1), Salmonella enteritidis (N=3) and Candida albicans (N=1). The contrast-enhanced computed-tomography disclosed an aneurysm whose diameter reached more than 50 mm (N=5), that increased rapidly in size (N=5), or presented an inflammatory aspect of the aortic wall (N=4). Management was both medical and interventional: surgery (N=3) or endoluminal repair (N=4). Outcome was favourable in six patients; one patient died from aneurysm-related complications. CONCLUSION: Clinical manifestations revealing an infectious thoracic aneurysm are variable. Diagnosis should be considered in patients presenting a rapidly-growing aneurysm, especially in the presence of elevated acute phase reactants. Endoluminal repair constitutes a treatment option. The role of FDG-PET for diagnosis and follow-up remains to be defined.

[Autoimmune diseases and cancers. Part I: cancers complicating autoimmune diseases and their treatment]. / Maladies auto-immunes et cancers. Première partie : cancers au cours des maladies auto-immunes et de leur traitement.

The link between systemic disease and cancer is not fortuitous. An autoimmune disease can represent the starter for developing a non-Hodgkin lymphoma. This is particularly true for Sjögren's syndrome that is associated with the highest risk of lymphoma (odds ratio up to 44). Other systemic autoimmune diseases concerned are systemic lupus with an odds ratio of 4.5 and rheumatoid arthritis with an odds ratio of 2 to 3. It is now well established that high inflammatory activity, rather than immunosuppressive treatment, is the major risk determinant. The association between solid cancer and autoimmune systemic disease is uncommon and concerns in particular scleroderma and lung cancer. Concerning biotherapy-induced cancers, there is no demonstrated increased risk with anti-TNFα (except for cutaneous carcinoma and maybe melanoma) or with tocilizumab and abatacept even if studies with longer follow-up are needed at least for these two last drugs.

[Is a patient's knowledge of cardiovascular risk factors better after the occurrence of a major ischemic event? Survey of 135 cases and 260 controls]. / La connaissance des facteurs de risque cardiovasculaire est-elle meilleure après la survenue d'un évènement ischémique majeur? Enquête auprès de 135 cas et 260 témoins.

AIM: We hypothezised that patients (cases) who are hospitalized for a major ischemic event--myocardial infarction, stroke, decompensation of peripheral arterial disease--acquire better knowledge than a control population--atheromatous patients without a major ischemic event, patients consulting for a vein disease or a diabetes evaluation, and accompanists--about cardiovascular risk factors (smoking, hypertension, diabetes, dyslipidemia, obesity) and have a better understanding of the usefulness of making changes in their lifestyle (quit smoking, regular exercise, Mediterranean diet, low salt diet, weight control, diabetes care). METHODS: A questionnaire was proposed at vascular surgery consultations and vascular and cardiac functional explorations, at the M Pavillon of the Édouard-Herriot hospital, Lyon, France. In five months, 395 questionnaires (135 cases and 260 controls) were analyzed. RESULTS: The global knowledge score was statistically higher for cases than for controls (cases 3.23±1.81; controls 2.77±2.03; P=0.037). Cases did not abide by monitoring and dietary rules better, except as regards the management of diabetes. Regular physical activity was statistically more prevalent among controls than among cases. Cases mainly received their information from their doctors (general practitioner for 59% of controls and 78% of cases, cardiologist for 25% of controls and 57% of cases) while controls got their information more through magazines or advertising. CONCLUSION: Our results show that after a major ischemic event, cases' knowledge of risk factors is better than the rest of the population without improved rules lifestyle changes. This suggests the usefulness of evaluating a therapeutic education program for atheromatous disease.

[Venous air emboli in a 4 year old child]. / Embolie gazeuse d'origine veineuse chez un enfant.

A 4 year old girl is referred to our institution for resection of a nephroblastoma with an extension of the tumor into the lumen of the inferior vena cava. To perform a correct resection of the tumor, the operation was conducted under cardiopulmonary bypass. At the end of the procedure, a bilateral mydriasis was noticed. A CT-scan concluded to a massive venous air emboli. As the procedure was unventful, and no other cause of air emboli was found, the etiology of this emboli is problably retrograde because of the large opening of the inferior vena cava that was required to remove the tumor. To avoid similar case the use of transcranial doppler monitoring may be of interest.

[Clopidogrel induced thrombotic thrombocytopenic purpura]. / Purpura thrombotique thrombocytopénique secondaire à l'utilisation du clopidogrel.

INTRODUCTION: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder. Drug-induced TTP is uncommon and we report a TTP associated with the use of clopidogrel. CASE REPORT: We report a 50-year-old man who presented with acute myocardial infarction and received clopidogrel therapy. He developed acute TTP ten days after clopidogrel onset. Imputability of the drug was demonstrated during a reintroduction test. Deficiency of ADAMTS 13 was confirmed and autoantibodies against ADAMTS 13 were detected. Complete remission was obtained after 24 plasma exchange sessions and adjunction of corticosteroids. CONCLUSION: Drug-induced TTP are probably immunologic, as was demonstrated in our patient. Clinicians should be aware of this possible uncommon adverse effect of clopidogrel because prompt therapy is imperative for life saving.

[Adult celiac disease with thrombosis: a case series of seven patients. Role of thrombophilic factors]. / Maladie cœliaque de l'adulte et thromboses : à propos de sept cas. Rôle des facteurs thrombophiliques.

PURPOSE: Thrombotic events may occur in celiac disease. In this study, we analyzed clinical features and risk factors for thrombosis in seven patients who had celiac disease and thrombosis. METHODS: We retrospectively studied 87 patients with adult celiac disease and identified seven cases of thrombosis. We searched if risk factors for thrombosis were identified and tested retrospectively antiphospholipid antibodies on the serum. RESULTS: In our study, the global prevalence of thrombosis was 8 %, and 5.7 % for spontaneous thrombosis, with venous thrombosis (n=5) or arterial thrombosis (n=1) or both (n=2). The seven patients consisted in six women and one man with a mean age of 44.8 years at time of thrombosis. Thrombotic events occurred before the diagnosis of celiac disease in four cases. In three cases, venous thrombosis was in unusual sites: portal (n=2), splenic vein thrombosis (n=1). In six cases, we identified risk factors for thrombosis, which could be linked to celiac disease: hyperhomocysteinemia (n=1), protein C and S deficiency due to vitamin K deficiency (n=3) and antiphospholipid antibodies (n=2). CONCLUSION: Such risk factors for thrombosis should be identified in patients in adult celiac disease in order to correct them and add a thromboembolic prophylaxis.

Esophageal dysmotility associated with systemic sclerosis: a high-resolution manometry study.

Esophageal involvement occurs in about 80% of patients with systemic sclerosis, with a marked diminution of peristaltic pressures in the distal two-thirds of the esophagus. Our aims were to more fully characterize esophageal motility disorders in systemic sclerosis using high-resolution manometry (HRM) and to determine predictive factors of esophageal involvement. Fifty-one patients (46 females) with systemic sclerosis were included in this retrospective study. Esophageal motility was characterized with HRM. The demographic data, esophageal symptoms, presence of other organ involvement, and autoantibody profile (anti-Scl70 antibodies [Scl70], anticentromere antibodies [ACA]) were recorded for all patients. Esophageal body dysmotility was present in 33 patients (67.3%) and was associated with hypotensive esophagogastric junction in 27 patients (55.1%). The velocity of proximal contractions was higher in patients with esophageal body dysmotility compared to patients with normal peristalsis (median 10.8 cm/s vs. 5.5, P = 0.04). The amplitude of middle esophageal contraction but not of distal esophageal contraction was reduced in patients with hypoperistalsis. Diffuse esophageal skin involvement, presence of Scl70 and absence of ACA were associated with esophageal involvement. Esophageal symptoms encountered in 87.5% of patients were not predictive of esophageal dysmotility. This HRM series confirms the high prevalence of esophageal body dysmotility in systemic sclerosis. Diffuse skin involvement, positive Scl70 and negative ACA, but not esophageal symptoms, may predict esophageal body dysmotility.

[Recurrent aseptic meningitis secondary to nonsteroidal anti-inflammatory drugs in a patient with lupus]. / Méningite aseptique récidivante due aux anti-inflammatoires non stéroïdiens chez une patiente lupique.

We report a 39-year-old woman with systemic lupus who presented with recurrent aseptic meningitis secondary to treatment with nonsteroidal anti-inflammatory drugs (NSAIDs). She presented two episodes following ibuprofen administration that were characterized by aseptic meningitis with high protein level in cerebrospinal fluid, and increased serum acute phase reactants. No evidence of an infection or vasculitis was documented. Clinical manifestation resolved rapidly with ibuprofen discontinuation, and corticosteroids therapy was unnecessary. Aseptic meningitis related to NSAIDs reported in lupus patients should be considered because of their specific modality of care and their favourable outcome.