Increased ischemic stroke, acute coronary artery disease and mortality in patients with granulomatosis with polyangiitis and microscopic polyangiitis.

OBJECTIVE: The aim of our study was to assess major cardiovascular event incidence, predictors, and mortality in ANCA-associated vasculitis (AAV). METHODS: We conducted a retrospective cohort study of all GPA or MPA, according to Chapel Hill Consensus Conference classification criteria, diagnosed between 1981 and 2015. Major cardiovascular event was defined as acute coronary artery disease, or ischemic stroke, or peripheral vascular disease requiring a revascularization procedure. We calculated the comparative morbidity/mortality figure (CMF) and we used Cox proportional hazards regression models to assess the risk of coronary artery disease, ischemic stroke associated with AAV, after adjusting for covariates. RESULTS: 125 patients, 99 GPA (79,2%) and 26 MPA (20,8%), were followed 88.4 ±â€¯78.3 months. Ischemic stroke incidence was four times higher than in the general population (CMF 4,65; 95% CI 4,06-5,31). Coronary artery disease incidence was four times higher than in the general population (CMF 4,22; 95% CI 1,52-11,68). Smoking habits and history of coronary artery disease were strongly associated with coronary artery disease occurrence (adjusted HR 8.8; 95% CI 2.12-36.56, and adjusted HR 10.3; 95% CI 1.02-104.5, respectively). ENT flare-up was an independent protective factor for coronary artery disease occurrence. We did not identify factors significantly associated with stroke occurrence. The age-adjusted mortality rate was 22.5 per 1000 person-years. Mortality in AAV was 1.5 times higher than in the general population (CMF 1.56; 95% CI 1.34-1.83). CONCLUSION: AAV have a significantly increased risk of mortality, ischemic stroke, and coronary artery disease.

[Prognostic value of procalcitonin, C-reactive protein and leukocytes in septic shock]. / Valor pronóstico del aclaramiento de procalcitonina, PCR y leucocitos en el shock séptico.

OBJECTIVES: This study evaluates the potential prognostic value of serial measurements of different biomarkers (procalcitonin [PCT], C-reactive protein and leukocytes [CRP]) in septic shock patients. DESIGN: Prospective observational study. SETTING: Intensive care unit of a third-level University Hospital. PATIENTS: The study comprised a total of 88 septic shock patients defined using the 2001 Consensus Conference SCCM/ESICM/ACCP/ATS/SIS criteria. The PCT, CRP and leukocytes were recorded on admission to the ICU and again 72 hours after admission. INTERVENTIONS: None. RESULTS: Those patients with increasing procalcitonin levels showed higher hospital mortality than those with a decreasing levels (58.8% vs. 15.4%, P<0.01). No such effect was observed in relation to C-reactive protein or leukocytes. The best area under the curve for prognosis was for procalcitonin clearance (0.79). A procalcitonin clearance of 70% or higher offered a sensitivity and specificity of 94.7% and 53%, respectively. CONCLUSIONS: Serial procalcitonin measurements are more predictive of the prognosis of septic shock patients than single measurements of this parameter. The prognostic reliability of the latter is also better than in the case of C-reactive protein and leukocytes. The application of serial procalcitonin measurements may allow the identification of those septic patients at increased mortality risk, and help improve their treatment.

Bilateral choroidopathy in systemic lupus erythematosus.

We report a case of bilateral choroidopathy in a 35-year-old woman with systemic lupus erythematosus (SLE) diagnosed 3 years previously, and treated with hydroxychloroquine and steroids that ceased 6 months before ocular signs. She complained about rapid bilateral blurred vision with a severe loss of visual acuity. Fluorescein angiography found multiple leakage points in the posterior pole of the pigment epithelium. Ocular coherence tomography (OCT) and fundoscopy showed bilateral retinal detachments. Lupus choroidopathy was diagnosed and high steroids were given intravenously and allowed a rapid improvement. Visual acuity, fundoscopy, retinal angiography and OCT were normalized at 2 months. Choroidopathy is rarely reported in lupus and only about 30 patients are found in the literature.

[TAFRO syndrome and cutaneous necrotizing vasculitis]. / Syndrome TAFRO et vascularite nécrosante cutanée : une association inédite.

INTRODUCTION: TAFRO syndrome is a systemic inflammatory syndrome in the spectrum of Castleman's disease, associating thrombocytopenia, anasarca, fever, renal failure and/or reticulin myelofibrosis and organomegaly. Its association with necrotizing cutaneous vasculitis has not yet been reported. CASE REPORT: A 69-year-old woman presented with weight loss, fever, anasarca, organomegaly, lymphadenopathy, anuria and extensive necrotic livedo occurring after acute diarrhea. Biology showed anemia, thrombocytopenia, renal failure, hypergammaglobulinemia, a circulating B-lymphocyte clone, hypoparathyroidism and autoimmune hypothyroidism. The skin biopsy showed small vessel vasculitis with fibrinoid necrosis. Methylprednisolone infusions associated with tocilizumab were ineffective and the patient became anuric. Rituximab and plasma exchanges associated to corticosteroids allowed remission for 2 months. Combination of rituximab, cyclophosphamide and dexamethasone resulted in a prolonged remission. CONCLUSION: We report here the first case of severe cutaneous necrotizing vasculitis in a patient suffering from TAFRO syndrome. The possible resistance to tocilizumab should be known.

[Clinical characteristics, outcome of scleromyxoedema: a retrospective multicentre study]. / Caractéristiques cliniques et évolutives du scléromyxœdème : étude rétrospective multicentrique.

BACKGROUND: scleromyxoedema is characterized by dermal mucin deposition associated with a monoclonal gammopathy. This is a rare disease, mostly reported as isolated cases. There is limited data regarding the course and prognosis of the disease. The aim of this study was to determine the clinical characteristics and course of scleromyxoedema. PATIENTS AND METHODS: this was a retrospective study in patients from five French university hospitals between 1987 and 2007. Data were collected using a standardized questionnaire. The inclusion criteria were based on the disease diagnosis criteria proposed by Rongioletti and Rebora: (1) generalized, papular and sclerodermiform skin eruption, (2) mucin deposition in the dermis, fibroblastic proliferation and skin fibrosis, (3) presence of a monoclonal gammopathy, (4) absence of thyroid disease. RESULTS: eight patients were included. The mean age at disease onset was 51.5 years (range: 35-67). The mean time from primary symptoms and diagnosis was 41.6 months (range: 4-120). Seven patients had extra-cutaneous involvement: four with peripheral neuropathy and three with interstitial pneumonia. The mean follow-up time was 9 years. Four patients improved: two experienced partial remission and two complete remission. Complete remission was obtained under treatment with dexamethasone (one patient) and thalidomide (one patient). One patient presented a myeloma and one patient presented encephalopathy leading to death. DISCUSSION: our study shows the frequency of extra-cutaneous involvement and shows that complete remission occurs in some patients.

[Development of sarcoma on a ectopic extramedullary hematopoiesis secondary to hereditary spherocytosis: Case report and literature review]. / Développement d'un sarcome sur foyer ectopique hématopoïétique secondaire à une sphérocytose héréditaire : à propos d'un cas et revue de la littérature.

INTRODUCTION: Extramedullary hematopoiesis is a complication of myeloproliferative neoplasms or of chronic hemolysis. The more frequent localizations are splenic, ganglionic or paraspinal. Rarely, extramedullary hematopoiesis is associated with solid cancer. CASE REPORT: We report an original case of sarcoma located in an extramedullary hematopoiesis mass in a 72-year-old woman suffering from hereditary spherocytosis. An asymptomatic right paravertebral mass was found in 2004; the biopsy confirmed extramedullary hematopoiesis. In 2016, the patient was hospitalized due to paravertebral pain. Computed tomography showed the extension of the right paraspinal mass to pleura and mediastinum as well as vertebral bone lysis. Positron emission tomography showed an intense hypermetabolism. The biopsy showed undifferentiated sarcoma. CONCLUSION: This case report illustrates the risk of neoplastic transformation of extramedullary hematopoiesis, and the need for a biopsy when confronted to atypical aspect.

Severe course of community-acquired pneumonia in an adult patient who is heterozygous for Q481P in the perforin gene: are carriers of the mutation free of risk?

Most cases of autosomal recessive hemophagocytic lymphohistiocytosis (HLH) are associated with over 50 mutations in the perforin gene. Some of these mutations have no clear functional association. Only homozygous patients display a full-blown syndrome, whereas no severe disease has been described in heterozygous carriers of these mutations despite the presence of functional and phenotypic alterations in cytotoxic cells. We study the family of a child who died from HLH at 6 months of age due to a Q481P mutation in the perforin gene. The study is particularly interesting because the patient's heterozygous father experienced severe community-acquired pneumonia that could be attributed to deficient in vitro NK cell activity despite normal perforin expression. This case report suggests that impaired NK cell activity in a heterozygote can result in poorer initial control of infections with severe clinical expression.

[Febrile myalgia revealing Propionibacterium acnes endocarditis]. / Myalgies fébriles révélant une endocardite infectieuse à Propionibacterium acnes.

INTRODUCTION: Propionibacterium acnes endocarditis is rare and difficult to diagnose. We report a case of Propioniacterium acnes endocarditis revealed by a lower limb fasciitis. CASE REPORT: A 54-year-old patient presented with recurrent febrile myalgia of the lower limbs, that appeared three years after an aortic surgery (aortic valve sparing reimplentation and ascending aortic prosthesis implantation). Computer tomography showed fasciitis of both legs. Positron emission tomography showed 18Fluorodeoxyglucose intake of the aortic prosthesis and in muscles of the lower limbs. Ten days after blood sample drawing, cultures showed the presence of Propionibacterium acnes. The aortic prosthesis was surgically removed, whose culture confirmed infection by Propionibacterium acnes. The diagnosis of infective endocarditis revealed by lower limb emboli was made. Evolution was favorable. CONCLUSION: In patients with vascular prostheses, Propionibacterium acnes infection must be evoked face to an atypical inflammatory process. Very prolonged blood culture incubation is needed to identify the pathogen.

[Wegener's granulomatosis with clinical manifestations of temporal arteritis]. / Une maladie de Wegener avec des signes d'artérite temporale.

A 51-year-old woman presented with crusting rhinitis, bilateral serous otitis, inflammatory arthralgias, fever, weight loss and signs of temporal arteritis. Temporal arteries were increased in size, painful, with inflammatory signs. There was microscopic hematuria and inflammatory parameters were increased. The renal function was normal. Anticytoplasmic neutrophils antibodies were detected (anti-PR3). Temporal artery biopsy did not show signs of giant cell arteritis. A diagnostic of Wegener's granulomatosis was established and steroid treatment allowed disappearance of clinical and biologic features.

[Fulminant alveolar hemorrhage: evolution of giant cell arteritis to ANCA-positive vasculitis?]. / Hémorragie intra-alvéolaire fulminante : transformation d'une maladie de Horton en vascularite ANCA-positive?

INTRODUCTION: Giant cell arteritis (GCA) is a granulomatous vasculitis of the large and medium size vessels with a remarkable sensitivity to corticosteroids, although it may be dependent to therapy. In rare cases, a vasculitis of the medium or small-size vessels may mimic, be associated to, or follow GCA. We report a case of GCA dependent to corticosteroids that was followed five years after diagnosis by an alveolar hemorrhage leading to the diagnosis of a possible Wegener's granulomatosis. EXEGESIS: A 70-year-old man had a diagnosis of GCA fulfilling the ACR criteria in 1999. Temporal artery biopsy revealed a typical histological pattern. The initial response to corticosteroids was excellent, but the patient became dependent to corticosteroids, so he was given methotrexate from 2002. Severe alveolar haemorrhage occurred in December 2004, leading to the diagnosis of possible ANCA positive, anti-proteinase 3 positive Wegener's granulomatosis. CONCLUSION: ANCA-positive vasculitis may complicate the course of GCA. This evolution should be rapidly recognized, because its treatment differs to that of GCA.

[Postural tachycardia syndrome (PoTS): An up-to-date]. / Le syndrome de tachycardie posturale (PoTS) : une maladie pour l'interniste.

Postural tachycardia syndrome (PoTS) is a multifactorial syndrome defined by an increase in heart rate ≥30bpm, within 10minutes of standing (or during a head up tilt test to at least 60°), in absence of orthostatic hypotension. It is associated with symptoms of cerebral hypoperfusion that are worse when upright and improve in supine position. Patients have an intense fatigue with a high incidence on quality of life. This syndrome can be explained by many pathophysiological mechanisms. It can be associated with Ehlers-Danlos disease and some autoimmune disorders. The treatment is based on nonpharmacological measures and treatment with propranolol, fludrocortisone or midodrine.

[A rarely diagnosed paraneoplastic syndrome: cerebral venous thrombosis]. / Un syndrome paranéoplasique rare: la thrombose veineuse cérébrale.

Cerebral venous thromboses are uncommon in cancer, and rarely presents as a paraneoplastic syndrome. A 42-year-old patient presented with headache and a bilateral papillar edema. Cerebral computed tomographic (CT) scan did not find a tumoral process. Biological tests disclosed increased acute phase reactants and liver cytolysis and cholestasis. Cerebral magnetic resonance angiogram showed superior longitudinal venous thrombosis. Thoracoabdominal CT scan was performed and disclosed multiple secondary liver nodules. CA 19-9 serum level was increased to 7648 UI/ml. Liver biopsy revealed a slightly differentiated mucinous adenocarcinoma compatible with a biliary tract or a pancreatic neoplasia. Chemotherapy with cisplatin and 5-fluorouracil was instituted but disease outcome was rapidly unfavourable.

[Angiosarcoma of the aorta]. / Angiosarcome épithélioïde de l'aorte.

Primary aortic tumors are extremely rare. A 73-year-old woman presented with a 8 kg weight loss associated with abdominal pain. Physical examination was normal. Laboratory tests disclosed increased acute phase reactants. Thoracic and abdominal CT scan showed diffuse splenic and renal hypodense lesions with thrombotic feature of the thoracic aorta extending on 9 cm length. Transesophageal echocardiography showed a large and heterogeneous floating mass advocating a thrombus developed on atheroma. Because of the high risk of embolism the patient underwent surgical replacement of the thoracic aorta. Histopathology revealed an epithelioid angiosarcoma of the aorta. A primary tumor of the aorta should be suspected in the presence of an intra-aortic process presenting features of thrombosis.

[Painful thoracic neuropathy disclosing Sjögren's syndrome: first report]. / Neuropathie thoracique douloureuse isolée: première description au cours d'une maladie de Gougerot.

INTRODUCTION: Thoracic neuropathy is rare, and is usually associated with diabetes mellitus. We report a first case of isolated multi-metameric thoracic neuropathy revealing Sjögren's disease. EXEGESIS: A 64-year old man consulted for symptoms suggesting a progressive and extensive (from T7 to T10) bilateral thoracic neuropathy. Diabetes mellitus and other causes of neuropathy were excluded. Spinal MRI, electromyography and CSF analysis were normal. Though the patient had no sicca syndrome symptoms, the diagnosis of Sjögren's syndrome was made on hypergammaglobulinemia, elevated ACAN (1/5000) with anti-SSA specificity and a grade III minor salivary gland biopsy. He improved spectacularly on corticosteroids (prednisone, 1 mg/kg/d). Sicca syndrome became clinically evident in April 2006. CONCLUSION: Pure sensitive thoracic neuropathy can reveal Sjögren's syndrome.

[Rituximab induced remission of pemphigus vulgaris: 2 cases]. / Pemphigus vulgaire évolutif sous corticoïdes et immunosuppresseurs: rémission sous rituximab. Deux observations.

INTRODUCTION: Pemphigus vulgaris frequently requires corticoids and immuno-suppressive drugs. The disease and the side effects of the drugs severely affect the quality of life, and sometime the vital prognosis of the patients. Other treatments than corticosteroids and immunosuppressive drugs are needed. EXEGESIS: We report 2 additional cases of pemphigus vulgaris uncontrolled by corticoids and immuno-suppressive drugs that responded spectacularly to rituximab. One patient had a recently onset disease, that was active despite 1,5 mg/kg/day prednisone and 1,5 g/day mycophenolate. She had a complete remission during 15 months after rituximab treatment. At relapse, another rituximab cycle led to a prompt remission. The other patient had longstanding pemphigus vulgaris complicated by cutaneous infections on prednisone (20 mg/d), immunosuppressive drugs and intravenous immune globulins. She had a prompt and complete remission after rituximab. CONCLUSION: Rituximab seems to be a promising drug for refractory pemphigus vulgaris. The benefit to risk ratio of this drug in this new indication must be precisely documented.

[Choroidal metastasis as a presenting feature of breast carcinoma]. / Métastase choroïdienne révélant un cancer du sein.

Choroidal metastasis is a rare presenting feature of breast carcinoma. A 48-year-old woman presented with blurred vision of the right eye related to choroidal metastasis. Diagnostic work-up disclosed breast carcinoma with multiple metastases of the liver and lungs. Initial cerebral computed tomography scan was normal. During the follow-up, generalized seizure leaded to the diagnosis of multiple calcified cerebral metastasis. In 15 to 30 percent of cases, choroidal metastasis reveals a solid tumor, usually of the lung or the breast. Cerebral metastasis are common in breast cancer, but rarely calcified.

Hypercapnic coma due to diaphragmatic involvement in a patient with dermatomyositis.

We report an acute respiratory distress by diaphragmatic involvement due to dermatomyositis. A fifty year-old patient with typical dermatomyositis presented an acute respiratory insufficiency with hypercapnic coma due to diaphragmatic muscle involvement. Respiratory state required mechanical ventilation initially and improved secondarily gradually upon corticosteroids and intravenous immunoglobulins. Only few cases of acute respiratory distress in dermatomyositis due to respiratory muscle involvement are reported in literature.

Cryptofolione derivatives from Cryptocarya alba fruits.

Cryptofolione (1) and the new cryptofolione derivative 6-(4,6-dimethoxy-8-phenyl-octa-1,7-dienyl)-4-hydroxy-tetrahydro-pyran-2-one (2) were isolated from the fruits of Cryptocarya alba. The structures were elucidated by spectroscopic methods. Cryptofolione showed activity towards Trypanosoma cruzi trypomastigotes, reducing their number by 77% at 250 microg mL(-1). Cryptofolione showed moderate cytotoxicity in both macrophages and T. cruzi amastigotes. It also displayed a mild inhibitory effect on the promastigote form of Leishmania spp. As both cytotoxic and trypanocidal effects are similar, the compound presented little selectivity in our assay models.