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EBV-positive inflammatory follicular dendritic cell sarcoma (EBV+ inflammatory FDCS) is a rare neoplasm almost exclusively located in the spleen or liver. It is characterized by a proliferation of EBV-positive spindle-shaped cells bearing follicular dendritic cell markers, associated with an abundant lymphoplasmacytic infiltrate. EBV+ inflammatory FDCS is often asymptomatic or responsible for mild symptoms. It usually displays an indolent course and its prognosis is excellent after tumor removal, although relapsing and metastatic forms exist. Herein, we describe an aggressive form of splenic EBV+ inflammatory FDCS in a 79-year-old woman presenting with abdominal pain, deterioration of general health status, major inflammatory syndrome, and symptomatic hypercalcemia. A splenectomy was performed leading to a rapid improvement in her clinical condition and normalization of laboratory abnormalities. Unfortunately, her symptoms and laboratory abnormalities reappeared 4 months later. Computed tomography showed a mass in the splenectomy site and multiple liver and peritoneal nodules. Further analyses were performed on tumor tissue and showed positive phospho-ERK staining of tumoral cells indicating activation of MAPK pathway. Inactivating mutations were found on CDKN2A and NF1 genes. Subsequently, the patient's condition deteriorated rapidly. Since interleukin-6 levels were dramatically increased, tocilizumab was used but only had a transient effect on the patient's symptoms and inflammatory syndrome. Antitumor agent gemcitabine was initiated but her clinical condition continued to deteriorate and the patient died 2 weeks later. The management of aggressive forms of EBV+ inflammatory FDCS remains challenging. However, since these tumors seem to display genetic alterations, better characterization could lead to molecular targeted therapies.
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Sarcoma de Células Dendríticas Foliculares , Neoplasias de Tecidos Moles , Feminino , Humanos , Idoso , Sarcoma de Células Dendríticas Foliculares/diagnóstico , Sarcoma de Células Dendríticas Foliculares/genética , Sarcoma de Células Dendríticas Foliculares/metabolismo , Baço/patologia , Herpesvirus Humano 4/genética , Recidiva Local de Neoplasia/patologia , Células Dendríticas Foliculares/metabolismo , Células Dendríticas Foliculares/patologia , Neoplasias de Tecidos Moles/patologiaRESUMO
OBJECTIVE: To identify characteristics of granulomatosis with polyangiitis (GPA) associated with induction failure, describe salvage therapies and their efficacy. METHODS: We conducted a nationwide retrospective case-control study of GPA with induction failure between 2006 and 2021. Each patient with induction failure was randomly paired to three controls matched for age, sex and induction treatment. RESULTS: We included 51 patients with GPA and induction failure (29 men and 22 women). At induction therapy, median age was 49 years. Twenty-seven patients received intravenous cyclophosphamide (ivCYC) and 24 rituximab (RTX) as induction therapy. Patients with ivCYC induction failure more frequently had PR3-ANCA (93% vs 70%, P = 0.02), relapsing disease (41% vs 7%, P < 0.001) and orbital mass (15% vs 0%, P < 0.01) compared with controls. Patients with disease progression despite RTX induction therapy more frequently had renal involvement (67% vs 25%, P = 0.02) with renal failure (serum creatinine >100 µmol/l in 42% vs 8%, P = 0.02) compared with controls. After salvage therapy, remission was achieved at 6 months in 35 (69%) patients. The most frequent salvage therapy was switching from ivCYC to RTX (or vice versa), showing an efficacy in 21/29 (72%). Remission was achieved in nine (50%) patients with inappropriate response to ivCYC, while in patients with progression after RTX induction, remission was achieved in four (100%) who received ivCYC (with or without immunomodulatory therapy), but only in three (50%) after adding immunomodulatory therapy alone. CONCLUSION: In patients with induction failure, characteristics of GPA, salvage therapies and their efficacy vary according to induction therapy and failure modality.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Granulomatose com Poliangiite , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/tratamento farmacológico , Estudos Retrospectivos , Estudos de Casos e Controles , Resultado do Tratamento , Rituximab/uso terapêutico , Ciclofosfamida/uso terapêutico , Fatores de Risco , Indução de RemissãoRESUMO
INTRODUCTION: Klebsiella pneumoniae (KP) is the most common cause of endogenous endophthalmitis (EE) in Asia, but data in Europe are scarce. We describe eight cases of KP EE compared to a cohort of EE in a French center. METHODS: EE cases were retrospectively studied between January 2014 and January 2021. KP EE cases were analyzed to assess clinical, microbiological features, and outcome. RESULTS: Among the 33 EE cases identified, the first causative agent (24%, n = 8) was KP, mainly (7/8) with hypervirulent phenotype (hvKP). All but one of these cases occurred from December 2019 to January 2021. Contrary to non-KP patients, KP patients had multiple extraocular infective foci (p = .006), all presented with liver abscesses (p < .001), 50% had cerebral involvement (p = .13). Visual outcome was poor in both groups. CONCLUSION: KP is an emerging cause of EE in a French center, consistently associated with liver abscesses, frequent cerebral involvement, and predominance of hvKP strains.
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Endoftalmite , Infecções por Klebsiella , Abscesso Hepático , Humanos , Virulência/genética , Klebsiella pneumoniae , Estudos de Coortes , Estudos Retrospectivos , Abscesso Hepático/diagnóstico , Abscesso Hepático/epidemiologia , Abscesso Hepático/complicações , Endoftalmite/diagnóstico , Endoftalmite/epidemiologia , Endoftalmite/complicações , Infecções por Klebsiella/diagnóstico , Infecções por Klebsiella/epidemiologia , Antibacterianos/uso terapêuticoRESUMO
OBJECTIVE: To help identify homogeneous subgroups among patients with anti-PM-scleroderma-antibodies (PM-Scl-Abs) positive auto-immune diseases regardless of diagnostic classifications. MATERIAL AND METHODS: This multicentric (four hospitals) retrospective study collected all consecutive patients (from 2011 to 2021) with positive testing for anti-PM-Scl-Abs in a context of CTD. Subgroups of patients with similar clinico-biological phenotypes were defined using unsupervised multiple correspondence analysis and hierarchical clustering analysis of the features recorded in the first year of follow-up. RESULTS: One hundred and forty-two patients with anti-PM-Scl-Abs were evaluated and 129 patients were included in the clustering analysis and divided into three clusters. Cluster 1 (n = 47) included patients with frequent skin thickening, digestive involvement and interstitial lung disease (ILD) with non-specific interstitial pneumonia (NSIP). They were more likely to develop progressive fibrosing ILD. Cluster 2 (n = 36) included patients who all featured NSIP with frequent organizing pneumonia-associated pattern and mechanic's hands. This subgroup had increased risk of relapse and ILD was characterized by a good functional outcome. Cluster 3 (n = 46) was characterized by predominant or isolated musculoskeletal involvement and frequently matched UCTD criteria. Although very frequent among anti-PM-Scl-Abs positive patients, muscle involvement was less discriminating compared with skin thickening and ILD pattern to classify patients into subgroups. CONCLUSION: Anti-PM-Scl-Abs associated auto-immune diseases are segregated into three subgroups with distinct clinical phenotype and outcomes. Skin thickening and NSIP are determinant predictors in segregation of theses populations.
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Doenças Pulmonares Intersticiais , Humanos , Estudos Retrospectivos , Prognóstico , Doenças Pulmonares Intersticiais/etiologia , Fenótipo , AutoanticorposRESUMO
Objective: to describe the prevalences, characteristics, and survivals of patients with anti-topoisomerase 1 antibodies (ATA) and limited cutaneous systemic sclerosis (lSSc) and anti-centromere antibodies (ACA) and diffuse cutaneous systemic sclerosis (dSSc). Methods: patients with ATA lSSc or with ACA dSSc were included in a case-control retrospective study. Results: In our cohort of scleroderma, the prevalence of ACA dSSc and ATA lSSc was 1.1% (12/1040) and 8.9% (93/1040), respectively. ACA dSSc patients had less interstitial lung disease (ILD) (5 (41.7) vs. 74 (79.6); p < 0.01), more cardiac involvement, and more muscle involvement (3 (25) vs. 4 (4.3); p = 0.03 and 4 (33.3) vs. 4 (7.5); p = 0.02,) than ATA dSSc patients. ATA lSSc patients had a higher modified Rodnan skin score than ACA lSSc patients (4 [2−7.5] vs. 2 [0−5]; p < 0.01) and less cardiac or muscle involvement than ATA dSSc patients (6 (6.5) vs. 19 (20.4%); p < 0.01 and 15 (16.1) vs. 54 (58.1); p < 0.0001, respectively). The cumulative 5-year survival rate was 71% in ACA dSSc patients, 95% in ATA lSSc patients, 84% in ACA lSSc patients, and 66% in ATA dSSc patients (p < 0.0001). Conclusion: ATA lSSc and ACA dSSc have specific characteristics when compared to ATA dSSc or ACA lSSc. ATA lSSc patients have more ILD than ACA lSSc patients, and ATA dSSc patients have the worst prognosis. Overall, inverted phenotypes show the value of a patient assessment combining antibody and skin subset and should be considered as a separate group.
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Erythroblastic synartesis is a rare cause of acquired dyserythropoiesis. Only 9 cases have been previously reported. We hereby report 3 cases of patients diagnosed with erythroblastic synartesis associated with monoclonal immunoglobulin and an overt malignant lymphoid disorder. A different B-cell clone may produce the monoclonal immunoglobulin, forming a biclonal disorder. In light of these data and literature review, treatment targeting the paraprotein seems to be efficient to control synartesis and correct anemia. In the case of monoclonal gammapathy associated with chronic lymphocytic leukemia, therapeutics should be adapted to control both chronic lymphocytic leukemia and monitored monoclonal immunoglobulin titer.
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Leucemia Linfocítica Crônica de Células B , Transtornos Linfoproliferativos , Paraproteinemias , Anticorpos Monoclonais , Eritroblastos/patologia , Humanos , Leucemia Linfocítica Crônica de Células B/patologia , Transtornos Linfoproliferativos/complicações , Paraproteinemias/complicaçõesRESUMO
BACKGROUND: Subglottic stenosis (SGS) and tracheal stenosis (TS) are characterized by a narrowing of the airways. The goal of this study was to describe the characteristics and prognosis of nontraumatic and nontumoral SGS or TS. RESEARCH QUESTION: What are the inflammatory etiologies of SGS and TS, and what are their characteristics and prognosis? STUDY DESIGN AND METHODS: This multicenter, observational retrospective study was performed in patients with SGS or TS that was neither traumatic nor tumoral. RESULTS: Eighty-one patients were included, 33 (41%) with granulomatosis with polyangiitis (GPA) and 21 (26%) with relapsing polychondritis (RP). GPA-related stenoses exhibited circumferential subglottic narrowing in 85% of cases, without calcifications. In contrast, RP-related stenoses displayed anterior involvement in 76%, in a longer distance from vocal cords (4 cm), with calcifications in 62%, and extension to bronchi in 86%. Other diagnoses included bullous dermatoses (n = 3), amyloidosis (n = 3), sarcoidosis (n = 2), and Crohn's disease (n = 2); the remaining stenoses (n = 15) were idiopathic. SGS/TS was the initial manifestation of the disease in 66% of cases, with a median interval from stenosis to disease diagnosis of 12 months (interquartile range, 0-48 months). Despite the use of glucocorticoids in 80%, combined with methotrexate in 49%, endoscopic procedures were required in 68% of patients. Relapses of stenoses occurred in 76% without any difference between causes (82% in GPA, 67% in RP, and 75% in idiopathic SGS/TS). Three patients died due to the stenosis, two of RP and one of GPA. INTERPRETATION: These data show that GPA and RP are the two main inflammatory diseases presenting with SGS/TS. GPA-related stenoses are mostly subglottic and circumferential, whereas RP-related stenoses are mostly tracheal, anterior, and calcified with a frequent extension to bronchi. Relapses of stenoses are common, and relapse rates do not differ between causes. Diagnosis and management of SGS/TS require a multidisciplinary approach.
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Granulomatose com Poliangiite/complicações , Laringoestenose/fisiopatologia , Policondrite Recidivante/complicações , Estenose Traqueal/fisiopatologia , Adulto , Amiloidose/complicações , Calcinose/diagnóstico , Calcinose/fisiopatologia , Doença de Crohn/complicações , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Laringoscopia/métodos , Laringoestenose/diagnóstico , Laringoestenose/etiologia , Laringoestenose/terapia , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Estudos Retrospectivos , Sarcoidose/complicações , Dermatopatias Vesiculobolhosas/complicações , Tomografia Computadorizada por Raios X , Estenose Traqueal/diagnóstico , Estenose Traqueal/etiologia , Estenose Traqueal/terapiaRESUMO
OBJECTIVE: The aim of this study was to describe the efficacy and safety of rituximab and MTX (RTX/MTX) combination therapy in ANCA-associated vasculitides (AAV). METHODS: A retrospective French nationwide study was conducted in patients with AAV who received RTX/MTX combination therapy for persistently active disease. RESULTS: Seventeen patients were included. All patients had granulomatosis with polyangiitis (GPA), with positive ANCA in 76% of them, mainly with PR3-ANCA specificity. Sixteen patients (94%) had priorly failed to achieve remission with RTX and 11 (65%) with CYC. Patients had experienced a median of 3 (2-4) flares. Manifestations requiring RTX/MTX combination therapy were subglottic or bronchial stenosis in 6 patients (35%), orbital mass in 6 (35%), disabling ENT involvement in 2 (12%), and epiduritis and pachymeningitis in 1 case (6%) each. The median follow-up duration for the RTX/MTX combination therapy was 11 months (11-26 months). At 6 months, global response had been achieved in 15 patients (88%), including partial response in 11 (65%) and complete response in 4 (24%). At last evaluation, global response had been achieved in 16 patients (94%). Seven patients (41%) experienced severe adverse events (grade 3 or 4), including infections in 4 (24%) and hepatitis in 2 (12%). Combination therapy was withdrawn in 4 patients (24%), but never for safety concerns. In contrast, the MTX dose was decreased in 2 patients (12%) because of adverse events. One patient died of an unknown cause. CONCLUSION: RTX/MTX combination therapy could be an effective salvage therapy to treat persistently active GPA with granulomatous manifestations, with an acceptable safety profile.
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Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Granulomatose com Poliangiite , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Anticorpos Anticitoplasma de Neutrófilos , Granulomatose com Poliangiite/tratamento farmacológico , Humanos , Metotrexato/uso terapêutico , Indução de Remissão , Estudos Retrospectivos , Rituximab/uso terapêutico , Terapia de Salvação , Resultado do TratamentoAssuntos
Aorta , Azetidinas/administração & dosagem , Imunossupressores/uso terapêutico , Purinas/administração & dosagem , Pirazóis/administração & dosagem , Artéria Subclávia , Sulfonamidas/administração & dosagem , Vasculite , Proteínas de Fase Aguda/análise , Aorta/diagnóstico por imagem , Aorta/patologia , Biópsia/métodos , Angiografia por Tomografia Computadorizada/métodos , Resistência a Medicamentos , Feminino , Humanos , Inibidores de Janus Quinases/administração & dosagem , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Artéria Subclávia/diagnóstico por imagem , Artéria Subclávia/patologia , Resultado do Tratamento , Vasculite/diagnóstico , Vasculite/tratamento farmacológico , Vasculite/imunologia , Vasculite/fisiopatologiaRESUMO
Objective: To explore pharmacokinetic/pharmacodynamic relationship between mycophenolic acid area under the curve and clinical response at 1 year on skin involvement or interstitial lung disease in patients with systemic sclerosis. Method: Retrospective, monocentric study based on French Scleroderma Database in patients receiving mycophenolate mofetil who experienced a limited sampling strategy to estimate individual mycophenolic acid area under the curve plus two pulmonary function tests and skin evaluation after 1 month and 1 year. Efficacy criterions were variations of modified Rodnan skin score, forced vital capacity, and diffusing lung capacity for carbon monoxide at 1 year. Results: We included 52 patients; mean age was 49 years (range 17-79), and 36 (69%) were females. Fifty patients (96%) had skin sclerosis, 39 (75%) had diffuse skin involvement with a median modified Rodnan skin score of 14 (0-38). Thirty-eight (76%) had interstitial lung disease, with median forced vital capacity and diffusing lung capacity for carbon monoxide of 81% (37-127) and 56% (28-103) from predicted values, respectively. Twenty-five (51%) patients had pulmonary fibrosis. Mycophenolate mofetil was given for 10 months (0-173) at a median dose of 2000 mg/day (500-3000). In the entire population, no relationship was found between area under the curve and modified Rodnan skin score (p = 0.085), forced vital capacity (p = 0.80), or diffusing lung capacity for carbon monoxide (p = 0.72) variations at 1 year. Conclusion: In this retrospective study, we failed to document any relationship between mycophenolic acid area under the curve and skin involvement or interstitial lung disease evolution. Routine monitoring of mycophenolic acid in systemic sclerosis patients treated with mycophenolate mofetil cannot be recommended based on our results.
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Objective: To determine the frequency of elevated D-dimer plasma concentration (>500 ng/mL) in patients with systemic sclerosis and evaluate its association with systemic sclerosis-specific microvascular and macrovascular complications. Methods: Retrospective observational study of patients with systemic sclerosis followed in a tertiary referral center with at least one measurement of D-dimer between 2010 and 2018. Results: A total of 214 patients were analyzed. Mean age at inclusion was 55.1 ± 14.7 years; 180 (84.1%) were female; 74 (34.6%) had diffuse cutaneous systemic sclerosis. Anti-Scl70 and anti-centromere antibodies were positive in 74 (34.6%) and 75 (35.0%) patients, respectively. D-dimer level was elevated in 93 (43.5%) patients, independently of cutaneous subtype (44.6% in diffuse cutaneous systemic sclerosis vs 42.9% in limited cutaneous systemic sclerosis, p = 0.81). At least one microvascular complication was found in 108 (50.5%) patients: 105 (49.1%) with previous or current digital ulcers, 6 (2.8%) with renal crisis, and 4 (1.9%) with pulmonary arterial hypertension. Microvascular complications were more frequent in patients with elevated D-dimer (57.0% vs 45.5%, p = 0.09), significantly so after exclusion of patients with a history of cancer and/or venous thromboembolism (60.5% vs 44.8%, p = 0.04). Macrovascular complications were detected in 15 (7.0%) patients and were associated with a high D-dimer level (11.8% vs 3.3%, p = 0.03). Over a median follow-up of 2.3 years [1.1-3.3] after D-dimer measurement, new macrovascular complications occurred only in patients with high D-dimer (n = 8). Conclusion: High D-dimer levels are frequently found in systemic sclerosis patients and seem to be associated with the occurrence of macrovascular and microvascular complications after adjustment for confounding factors.
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BACKGROUND: Although the efficacy of lopinavir/ritonavir has not been proven, it has been proposed as an off-label treatment for COVID-19. Previously, it has been reported that the plasma concentrations of lopinavir significantly increase in inflammatory settings. As COVID-19 may be associated with major inflammation, assessing the plasma concentrations and safety of lopinavir in COVID-19 patients is essential. METHODS: Real-world COVID-19 data based on a retrospective study. RESULTS: Among the 31 COVID-19 patients treated with lopinavir/ritonavir between March 18, 2020 and April 1, 2020, higher lopinavir plasma concentrations were observed, which increased by 4.6-fold (interquartile range: 3.6-6.2), compared with the average plasma concentrations in HIV. Lopinavir concentrations in all except one patient were above the upper limit of the concentration range of HIV treatment. Approximately one to 5 patients prematurely stopped treatment mainly because of an ADR related to hepatic or gastrointestinal disorders. CONCLUSIONS: Lopinavir plasma concentrations in patients with moderate-to-severe COVID-19 were higher than expected, and they were associated with the occurrence of hepatic or gastrointestinal adverse drug reactions. However, a high plasma concentration may be required for in vivo antiviral activity against SARS-CoV-2, as suggested by previous studies. Therefore, in the absence of adverse drug reaction, lopinavir dosage should not be reduced. Caution is essential because off-label use can be associated with a new drug safety profile.
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Antivirais/sangue , Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Lopinavir/sangue , Lopinavir/uso terapêutico , Ritonavir/sangue , Ritonavir/uso terapêutico , Idoso , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Comorbidade , Combinação de Medicamentos , Feminino , Humanos , Lopinavir/administração & dosagem , Lopinavir/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ritonavir/administração & dosagem , Ritonavir/efeitos adversos , SARS-CoV-2 , Índice de Gravidade de DoençaRESUMO
INTRODUCTION: Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs). Among them, ICIs-induced systemic sclerosis (SSc) is poorly known. METHODS: To better characterize this irAE, our comprehensive approach combined the description of ICIs-induced scleroderma cases, the systematic review of the literature and the analysis of VigiBase, the WHO pharmacovigilance database. RESULTS: We identified two cases with underlying limited cutaneous SSc who presented a dramatic increase in the skin thickening following pembrolizumab, associated with scleroderma renal crisis in one case. In the literature, four cases of scleroderma and four cases of morphea have been reported with pembrolizumab or nivolumab. None following ipilimumab, atezolizumab or durvalumab were retrieved. Skin changes appeared or worsened more quickly with pembrolizumab than nivolumab, and had different patterns between both drugs. Patients with generalized skin changes required high-dose prednisone to improve skin thickening. Among the 2527 scleroderma cases identified in VigiBase, 35 were associated with ICIs. Nivolumab and pembrolizumab showed a disproportionality in scleroderma reporting. No disproportionality was found for ipilimumab, atezolizumab or durvalumab. CONCLUSION: The risk of scleroderma or fibrosis extension in SSc patients should be considered when initiating anti-PD-1 agents. It suggests the role of PD-1/PD-L1 interaction in the pathophysiology of SSc.
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Antineoplásicos Imunológicos , Neoplasias , Escleroderma Sistêmico , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/classificação , Antineoplásicos Imunológicos/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico , Risco , Escleroderma Sistêmico/induzido quimicamenteRESUMO
OBJECTIVE: To assess the effectiveness of hydroxychloroquine in patients admitted to hospital with coronavirus disease 2019 (covid-19) pneumonia who require oxygen. DESIGN: Comparative observational study using data collected from routine care. SETTING: Four French tertiary care centres providing care to patients with covid-19 pneumonia between 12 March and 31 March 2020. PARTICIPANTS: 181 patients aged 18-80 years with documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia who required oxygen but not intensive care. INTERVENTIONS: Hydroxychloroquine at a dose of 600 mg/day within 48 hours of admission to hospital (treatment group) versus standard care without hydroxychloroquine (control group). MAIN OUTCOME MEASURES: The primary outcome was survival without transfer to the intensive care unit at day 21. Secondary outcomes were overall survival, survival without acute respiratory distress syndrome, weaning from oxygen, and discharge from hospital to home or rehabilitation (all at day 21). Analyses were adjusted for confounding factors by inverse probability of treatment weighting. RESULTS: In the main analysis, 84 patients who received hydroxychloroquine within 48 hours of admission to hospital (treatment group) were compared with 89 patients who did not receive hydroxychloroquine (control group). Eight additional patients received hydroxychloroquine more than 48 hours after admission. In the weighted analyses, the survival rate without transfer to the intensive care unit at day 21 was 76% in the treatment group and 75% in the control group (weighted hazard ratio 0.9, 95% confidence interval 0.4 to 2.1). Overall survival at day 21 was 89% in the treatment group and 91% in the control group (1.2, 0.4 to 3.3). Survival without acute respiratory distress syndrome at day 21 was 69% in the treatment group compared with 74% in the control group (1.3, 0.7 to 2.6). At day 21, 82% of patients in the treatment group had been weaned from oxygen compared with 76% in the control group (weighted risk ratio 1.1, 95% confidence interval 0.9 to 1.3). Eight patients in the treatment group (10%) experienced electrocardiographic modifications that required discontinuation of treatment. CONCLUSIONS: Hydroxychloroquine has received worldwide attention as a potential treatment for covid-19 because of positive results from small studies. However, the results of this study do not support its use in patients admitted to hospital with covid-19 who require oxygen.
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Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxigenoterapia , Pandemias , Adulto JovemRESUMO
INTRODUCTION: We conducted a retrospective multicenter cohort study of patients receiving Immunoglobulin replacement therapy (IgRT) for secondary immune deficiency (SID) during 2012. METHODS: Data were retrospectively collected from the first dose of Ig administered in 2012 to 1 year afterward in terms of the indication for IgRT, as well as efficacy and safety. RESULTS: In total, 16 hospitals participated in the study, and 368 patients were included. Indications for IgRT were non-Hodgkin lymphoma (82 [22.3%] patients), multiple myeloma (76 [20.7%]), chronic lymphocytic leukemia (64 [17.4%]) and other (79 [21.5%]). Only 89 (24.2%) patients received IgRT according to 2011 European Medical Agency (EMA) recommendations; 196 (53.3%) received prophylactic antibiotics and 262 (76.2%) had an IgG level < 4 g/L before IgRT initiation. CONCLUSION: In this study, whatever the criteria, only 24.2% of patients with SID who received IgRT met EMA recommendations, which suggests a misuse of IgRT in SID.
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Imunoglobulinas Intravenosas/administração & dosagem , Síndromes de Imunodeficiência/imunologia , Síndromes de Imunodeficiência/terapia , Administração Cutânea , Feminino , Neoplasias Hematológicas/imunologia , Humanos , Testes Imunológicos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Catastrophic antiphospholipid syndrome is the most severe complication of antiphospholipid syndrome. Vitamin K antagonists are the reference treatment for preventing relapsing thrombotic complications in patients with antiphospholipid syndrome. Direct oral anticoagulants are nonetheless sometimes used in this setting. We report two cases of women who were triple-positive for antiphospholipid antibodies and developed catastrophic antiphospholipid syndrome in the week after the introduction of rivaroxaban. The first patient, who had had a previous thrombotic event, had multiorgan failure 3 days after vitamin K antagonists was replaced by rivaroxaban, and the second developed a similar clinical presentation 7 days after introduction of the same treatment. Both catastrophic antiphospholipid syndrome episodes were successfully treated with heparin followed by vitamin K antagonists, corticosteroids, and plasmapheresis. These two cases highlight for the inefficacy of rivaroxaban preventing severe thrombotic events such as catastrophic antiphospholipid syndrome and thus provide further support for recommendations that vitamin K antagonists must remain the reference anticoagulant in patients with triple-positive antiphospholipid antibodies.
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Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/fisiopatologia , Rivaroxabana/efeitos adversos , Corticosteroides/uso terapêutico , Adulto , Idoso , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/tratamento farmacológico , Doença Catastrófica , Feminino , Heparina/uso terapêutico , Humanos , Rivaroxabana/uso terapêutico , Trombose/tratamento farmacológicoRESUMO
In systemic sclerosis (SSc), the use of corticosteroids (CS) is controversial due to their association with scleroderma renal crisis (SRC). However, patients with very early and early disease, characterised by main inflammatory component, may benefit from CS therapy. The aim of this review is to discuss pros and cons of CS treatment in SSc, providing current evidence about the use of CS in SSc. Moreover, we discuss also the underlying pathogenetic mechanisms that may be the background for the potential harms and efficacy of CS in SSc.
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Corticosteroides/efeitos adversos , Escleroderma Sistêmico/tratamento farmacológico , Humanos , Nefropatias/etiologia , Escleroderma Sistêmico/complicaçõesRESUMO
Glomeruloid haemangioma (GH) is considered a specific marker of POEMS syndrome, despite some published GH cases unrelated to POEMS syndrome. To present two cases with GH and atypical presentations of Erdheim-Chester disease (ECD) or POEMS syndrome, as well as a retrospective monocentric study of histologically-confirmed GH. Clinical, biological and histological data of the patients is presented. In addition to the two presented cases, 11 GH histologically-confirmed cases were retrospectively identified. Six patients were female (46.2%; 95 CI: 12-64.9) and median age was 54 years (31-85). For 11 patients (84.6%; 95 CI: 65-104.2), a diagnosis of POEMS syndrome was retained, one patient had autoimmune hepatitis, and another had ECD. GH was localised to the trunk in 10 cases (76.9%; 95 CI: 54-99) and the legs in the other three. The median number of haemangiomas in the cohort was three (SD: 3.08). Median level of VEGF was 1,490 (610-12,000) ng/mL. All immunohistochemical staining for human herpesvirus 8 (HHV-8) was negative. Of the 13 cases of GH, of which two were not clear-cut POEMS syndrome, we report the first case of GH associated with ECD. In this cohort, all patients had high serum levels of VEGF but no in situ HHV-8 latent infection. We hypothesise that GH might be linked to a high level of VEGF in these two rare diseases.
Assuntos
Doença de Erdheim-Chester/sangue , Hemangioma/patologia , Síndrome POEMS/sangue , Neoplasias Cutâneas/patologia , Fator A de Crescimento do Endotélio Vascular/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Erdheim-Chester/complicações , Feminino , Hemangioma/sangue , Hemangioma/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome POEMS/complicações , Estudos Retrospectivos , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/etiologia , Carga TumoralRESUMO
Anti-endothelial cell antibodies (AECAs) are those that can bind to endothelial cells (ECs) via variable region-specific interactions. The identification and quantification of AECAs varies depending on the technique used. The best approach would be to combine at least two different methods. Thus, AECA measurement cannot be considered a diagnostic tool, but the detection and titers of AECAs are associated with disease activity in various systemic vasculitis diseases. AECAs have been described in almost all primary systemic vasculitis diseases but also in many secondary vasculitis diseases, with the identification of various antigens. AECAs may play a pathogenic role in vasculitis, both in vitro and in vivo, mainly via EC activation and induction of apoptosis. We used a systematic review of the literature to better define the prevalence, clinical association, targeted antigens, possible pathophysiologic role and clinical usefulness of AECAs in various types of vasculitis.