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BACKGROUND: Randomized clinical trials have demonstrated efficacy and safety of erenumab. The aim of this study is to evaluate the effectiveness and safety of erenumab in a real-world setting in French patients with migraine associated with extreme unmet needs. METHODS: This is a one year-prospective real-word study with enrolment of all consecutive adult patients included in the FHU InovPain registry who participated in a compassionate erenumab use program. RESULTS: Of 144 patients included, 140 patients (82.1% female / mean age of 50.9 ± 11.4) received at least one dose of erenumab and were concerned by effectiveness and safety assessment. All patients had failed 11 oral preventive treatments. Most of them suffered from chronic migraine (88.6%) and presented a medication overuse (90.7%) at baseline. Thirty-eight (27.1%) discontinued treatment during the 12-month follow-up, with 22 (15.7%), 11 (7.9%) and 5 (3.6%) patients before 3, 6 or 9 months of treatment. The proportion of ≥ 50% responders at M3, M6, M9 and M12 was 74/140 (52.9%), 69/118 (58.5%), 61/107 (57.0%) and 60/102 (58.8%) respectively. At M3, the rate of reversion from chronic migraine to episodic migraine was 57.3% and the rate of transition from medication overuse to non-overuse was 46.5%. For monthly migraine days, the median (IQR) was 18.0 (13.0-26.0), 9.0 (5.0-17.0), 7.5 (5.0-14.0), 8.0 (5.0-12.5) and 8.0 (5.0-12.0) at M0, M3, M6, M9 and M12 respectively. For HIT-6 score, the median (IQR) was 68.0 (63.8-73.3), 60.0 (54.0-65.0), 60.0 (50.3-53.0), 59.0 (50.0-63.0) and 58.0 (50.0-62.9) at M0, M3, M6, M9 and M12 respectively. Fifty-three (37.9%) patients reported at least one of the following adverse events: cutaneous erythema and/or pain at the injection site for 42 (30%) patients, constipation for 22 (15.7%) patients, muscle spasm for 2 (1.4%) patients, alopecia for one (0.7%) patient and blood pressure increase in one (0.7%) patient. There was no serious adverse event. One female patient became pregnant after 5 months of exposure to erenumab with a safe evolution after treatment discontinuation. CONCLUSION: This first French real-world study related to migraine prevention with CGRP-mAbs confirms effectiveness and safety of erenumab in patients with extreme unmet needs.
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Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina , Transtornos de Enxaqueca , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Prospectivos , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/uso terapêutico , Método Duplo-Cego , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/prevenção & controle , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: Systemic lupus erythematosus (SLE) is an immune-mediated disease that may affect the nervous system. We explored the topographical organization of structural and functional brain connectivity in patients with SLE and its correlation with neuropsychiatric (NP) involvement and autoantibody profiles. METHODS: Graph theoretical analysis was applied to diffusion tensor magnetic resonance imaging (MRI) and resting-state functional MRI data from 32 patients with SLE and 32 age- and sex-matched healthy controls. Structural and functional connectivity matrices between 116 cortical/subcortical brain regions were estimated using a bivariate correlation analysis, and global and nodal network metrics were calculated. RESULTS: Structural, but not functional, global network properties (strength, transitivity, global efficiency and path length) were abnormal in patients with SLE versus controls (P < 0.0001), especially in patients with anti-double-stranded DNA (ADNA) autoantibodies (P = 0.03). No difference was found according to NP involvement or anti-phospholipid autoantibody status. Patients with SLE and controls shared identical structural hubs and the majority of functional hubs. In patients with SLE, all structural hubs showed reduced strength and clustering coefficient compared with controls (P from 0.001 to <0.0001), especially in patients with ADNA autoantibodies. Only a few differences in functional hub properties were found between patients with SLE and controls. Structural and functional hub measures did not differ according to NP involvement or anti-phospholipid autoantibody status. Significant correlations were found between clinical, MRI and network measures (r from -0.56 to 0.60, P from 0.0003 to 0.05). CONCLUSIONS: Abnormalities of global and nodal structural connectivity occur in patients with SLE, especially with ADNA autoantibodies, with a diffuse disruption of structural integrity. Functional network integrity may contribute to preserve clinical functions.
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Encéfalo/patologia , Conectoma , Lúpus Eritematoso Sistêmico/patologia , Adulto , Anticorpos Antifosfolipídeos/análise , Anticorpos Antifosfolipídeos/imunologia , Autoanticorpos/imunologia , Encéfalo/diagnóstico por imagem , Córtex Cerebral/patologia , Análise por Conglomerados , DNA/imunologia , Imagem de Tensor de Difusão , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/imunologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND AND AIM: Patients with Systemic Lupus Erythematosus (SLE) present increased cardiovascular mortality compared to the general population. Few studies have assessed the long-term development and progression of carotid atherosclerotic plaque in SLE patients. Our aim was to investigate the association of clinical and laboratory markers of disease activity and classical cardiovascular risk factors (CVRF) with carotid atherosclerosis development in SLE patients in a prospective 5-year study. METHODS AND RESULTS: Clinical history and information on principal CVRFs were collected at baseline and after 5 years in 40 SLE patients (36 women, mean age 42 ± 9 years; 14.4 ± 7 years of mean disease duration) and 50 age-matched controls. Carotid Doppler ultrasonography was employed to quantify the atherosclerotic burden at baseline and at follow up. Clinimetrics were applied to assess SLE activity over time (SLEDAI). The association between basal circulating T cell subsets (including CD4+CCR5+; CD4+CXCR3+; CD4+HLADR+; CD4+CD45RA+RO-, CD4+CD45RO+RA- and their subsets) and atherosclerosis development was evaluated. During the 5-year follow up, 32% of SLE patients, developed carotid atherosclerosis compared to 4% of controls. Furthermore, considering SLEDAI changes over time, patients within the highest tertile were those with increased incidence of carotid atherosclerosis independently of CVRF. In addition, increased levels of CD4+CCR5+ T cells were independently associated with the development of carotid atherosclerosis in SLE patients. CONCLUSION: Serial clinical evaluations over time, rather than a single point estimation of disease activity or CVRF burden, are required to define the risk of carotid atherosclerosis development in SLE patients. Specific T cell subsets are associated with long-term atherosclerotic progression and may further be of help in predicting vascular disease progression.
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Linfócitos T CD4-Positivos/imunologia , Doenças das Artérias Carótidas/imunologia , Proliferação de Células , Lúpus Eritematoso Sistêmico/imunologia , Receptores CCR5/imunologia , Adulto , Biomarcadores/sangue , Linfócitos T CD4-Positivos/metabolismo , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/diagnóstico , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Receptores CCR5/sangue , Medição de Risco , Fatores de Risco , Fatores de Tempo , Ultrassonografia DopplerRESUMO
OBJECTIVES: To describe the clinical features, treatment response, and follow-up of a large cohort of Italian patients with immunoglobulin (Ig)G4-related disease (IgG4-RD) referred to a single tertiary care centre. METHOD: Clinical, laboratory, histological, and imaging features were retrospectively reviewed. IgG4-RD was classified as 'definite' or 'possible' according to international consensus guidelines and comprehensive diagnostic criteria for IgG4-RD. Disease activity was assessed by means of the IgG4-RD Responder Index (IgG4-RD RI). RESULTS: Forty-one patients (15 females, 26 males) were included in this study: 26 with 'definite' IgG4-RD and 15 with 'possible' IgG4-RD. The median age at diagnosis was 62 years. The median follow-up was 36 months (IQR 24-51). A history of atopy was present in 30% of patients. The pancreas, retroperitoneum, and major salivary glands were the most frequently involved organs. Serum IgG4 levels were elevated in 68% of cases. Thirty-six patients were initially treated with glucocorticoids (GCs) to induce remission. IgG4-RD RI decreased from a median of 7.8 at baseline to 2.9 after 1 month of therapy. Relapse occurred in 19/41 patients (46%) and required additional immunosuppressive drugs to maintain long-term remission. Multiple flares occurred in a minority of patients. A single case of orbital pseudotumour did not respond to medical therapy and underwent surgical debulking. CONCLUSIONS: IgG4-RD is an elusive inflammatory disease to be considered in the differential diagnosis of isolated or multiple tumefactive lesions. Long-term disease control can be achieved with corticosteroids and immunosuppressive drugs in the majority of cases.
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Doenças Autoimunes/imunologia , Glucocorticoides/uso terapêutico , Imunoglobulina G/imunologia , Imunossupressores/uso terapêutico , Pancreatite/imunologia , Sialadenite/imunologia , Idoso , Doenças Autoimunes/complicações , Doenças Autoimunes/tratamento farmacológico , Estudos de Coortes , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Pseudotumor Orbitário/etiologia , Pseudotumor Orbitário/imunologia , Pseudotumor Orbitário/cirurgia , Pancreatite/tratamento farmacológico , Pancreatite/etiologia , Recidiva , Indução de Remissão , Espaço Retroperitoneal , Estudos Retrospectivos , Sialadenite/tratamento farmacológico , Sialadenite/etiologiaRESUMO
BACKGROUND AND AIM: Patients with systemic lupus erythematosus (SLE) have a higher prevalence of subclinical atherosclerosis and higher risk of cardiovascular (CV) events compared to the general population. The relative contribution of CV-, immune- and disease-related risk factors to accelerated atherogenesis in SLE is unclear. METHODS AND RESULTS: Fifty SLE patients with long-lasting disease (mean age 44 ± 10 years, 86% female) and 50 sex- and age-matched control subjects were studied. Common carotid artery intima-media thickness (CCA-IMT) was used as a surrogate marker of atherosclerosis. We evaluated traditional and immune- and disease-related factors, assessed multiple T-cell subsets by 10-parameter-eight-colour polychromatic flow cytometry and addressed the effect of pharmacological therapies on CCA-IMT. In SLE patients, among several cardiometabolic risk factors, only high-density lipoprotein levels (HDL) and their adenosine triphosphate-binding cassette transporter 1 (ABCA-1)-dependent cholesterol efflux capacity were markedly reduced (p < 0.01), whereas the CCA-IMT was significantly increased (p = 0.03) compared to controls. CCA-IMT correlated with systolic blood pressure, low-density lipoprotein (LDL) cholesterol and body mass index (BMI), but not with disease activity and duration. The activated CD4(+)HLA-DR(+) and CCR5(+) T-cell subsets were expanded in SLE patients. Patients under hydroxychloroquine (HCQ) therapy showed lower CCA-IMT (0.62 ± 0.08 vs. 0.68 ± 0.10 mm; p = 0.03) and better risk-factor profile and presented reduced circulating pro-atherogenic effector memory T-cell subsets and a parallel increased percentage of naïve T-cell subsets. CONCLUSION: HDL represents the main metabolic parameter altered in SLE patients. The increased CCA-IMT in SLE patients may represent the net result of a process in which 'classic' CV risk factors give a continuous contribution, together with immunological factors (CD4(+)HLA-DR(+) T cells) which, on the contrary, could contribute through flares of activity of various degrees over time. Patients under HCQ therapy present a modified metabolic profile, a reduced T-cell activation associated with decreased subclinical atherosclerosis.
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Doenças Cardiovasculares/sangue , Artéria Carótida Primitiva/fisiopatologia , Espessura Intima-Media Carotídea , Fatores Imunológicos/metabolismo , Lúpus Eritematoso Sistêmico/sangue , Transportador 1 de Cassete de Ligação de ATP/sangue , Adulto , Biomarcadores/sangue , Pressão Sanguínea/efeitos dos fármacos , Índice de Massa Corporal , Linfócitos T CD4-Positivos/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Artéria Carótida Primitiva/efeitos dos fármacos , Estudos de Casos e Controles , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Modelos Logísticos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de RiscoRESUMO
PURPOSE: Optic nerve sheath fenestration (ONSF) is a surgical procedure commonly performed in the Anglo-Saxon countries for the treatment of medically refractory idiopathic intracranial hypertension (IIH). We chose to compare 6 different trans-orbital surgical approaches to ONSF. We also desired to determine the number of optic nerve decompression procedures performed in France in 2019 and 2020. METHODS: Four fresh frozen orbits were dissected at the University of Nice anatomy laboratory. We performed the following surgical approaches: (i) eyelid crease, (ii) lid-split, (iii) medial transconjunctival with medial rectus disinsertion, (iv) medial transconjunctival without rectus disinsertion, (v) lateral transconjunctival and (vi) lateral orbitotomy. For each surgical approach, we measured the distance between the incision and the optic nerve dura mater. We also extracted data from the French National PMSI (Programme de Médicalisation des Systèmes d' Information) database from January 2019 through December 2020 to determine the annual number of optic nerve decompression procedures. RESULTS: The lid crease and medial transconjunctival approaches provided the shortest distance to the optic nerve (average 21mm and 24mm, respectively) and the lowest levels of difficulty compared to the other surgical routes. A total of 23 and 45 optic nerve decompressions were performed in France in 2019 and 2020, respectively. Among them, only 2 and 7 procedures, respectively, were performed through a trans-orbital approach. CONCLUSION: Upper lid crease incision and medial transconjunctival approaches are the most direct and easiest surgical routes when performing an ONSF. We found that ONSF was rarely performed in France. We strongly recommend close cooperation between ophthalmologists, neurologists, neurosurgeons and interventional radiologists.
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Nervo Óptico , Pseudotumor Cerebral , Humanos , Nervo Óptico/cirurgia , Pseudotumor Cerebral/cirurgia , Descompressão Cirúrgica/métodos , Pálpebras/cirurgia , França/epidemiologiaRESUMO
INTRODUCTION: The application of de Seze et al. criteria (2007) to patients presenting a first severe acute demyelinating event helps to distinguish acute disseminated encephalomyelitis (ADEM) from other CNS inflammatory diseases, with 83% sensitivity and 95% specificity. We applied these criteria to 14 patients who presented a first severe acute demyelinating event and whose later clinical course enabled clear identification of the neurological diagnosis. METHOD/PATIENTS: This study concerned 14 patients who presented a first acute demyelinating event. Initially, there were 16 patients but two were excluded because their initial clinical condition (isolated acute retrobulbar optic neuritis in one and acute cervical myelitis in the other) would have excluded them in the princeps article. We identified 11 women (78.6%) and three men (21.4%) with a mean age of 33.7+/-12.5 years. Follow-up ranged from three months to 11.5 years after the initial episode (average four years). At last follow-up, the diagnosis was ADEM in seven patients (50%) and multiple sclerosis (MS) in seven (50%). Five of seven patients in the MS group had a tumor-like presentation (71.4%), this parameter partly explaining the initial discrepancy in diagnosis. When applied to our series, de Seze criteria for ADEM exhibited 85.7% sensitivity and 71.4% specificity. CONCLUSION: Applying the new criteria, we did not find the same sensitivity, specificity, and positive and negative predictive values as in the original article. The lack of specificity arose from the misclassification of MS patients with a tumor-like presentation (two out of five false negatives). One of the explanations is that the clinical criteria used can be part of atypical forms of MS, in particular in its tumor-like presentation. De Seze et al. criteria can be an invaluable help for the clinician in the diagnosis of a first severe demyelinating event. Considering our results, these criteria should not be applied for patients with a tumor-like form of MS. A prospective study in a larger cohort is needed to confirm or invalidate these preliminary results.
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Doenças Desmielinizantes/diagnóstico , Exame Neurológico/normas , Adulto , Afasia/diagnóstico , Diagnóstico Diferencial , Encefalite/diagnóstico , Encefalomielite Aguda Disseminada/diagnóstico , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico , Adulto JovemRESUMO
INTRODUCTION: Intravenous thrombolysis with rt-Pa in stroke has been approved in France since 2002. We report an evaluation of our practice. We have tried to identify predictive factors of dependence and death, and to compare our results with the data of the literature. PATIENTS AND METHOD: All patients treated with intravenous rt-PA within the first 270min after the stroke onset were included. Univariate, then multivariate analyses were performed to determine the variables influencing the functional outcome at 3 months follow-up, according to a dichotomy established from the modified Rankin scale. RESULTS: One hundred and forty-two patients were included in this study (mean initial National Institute of Health Stroke Scale [NIHSS]: 15). Fifty percent had a Rankin score higher than 2 at 3 months follow-up. NIHSS above 12, glycemia of at least 120mg/l, and systolic blood pressure above 160mmHg at admission were identified as independent predictive factors of poor functional outcome. Less than 4 points decrease of NIHSS proved to be a simple and early predictor of poor functional outcome at 3 months follow-up. CONCLUSIONS: In terms of safety and efficacy the data issuing from the daily activity of our stroke unit are comparable with those of clinical trials.
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Fibrinolíticos/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Ensaios Clínicos como Assunto , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Segurança , Ativador de Plasminogênio Tecidual/administração & dosagemRESUMO
We report the case of a 49-year-old man who was admitted for progressive behaviorial disorders with frontal elements. There was no sensorial nor motor deficiency. Clinical examination revealed android obesity, cutaneous and mucous paleness, pubic and axillary depilation and gynecomastia. Encephalic MRI found a lesion of the left amygdalian region with high T2 intensity and low T1 intensity associated with gadolinium-enhancement. Cerebrospinal fluid analysis showed a lymphocytic meningitis. Panhypopituitarism was found on the endocrine investigations. Anti-RI antibodies were positive, leading to the diagnosis of paraneoplastic limbic encephalitis. The CT-scan showed a node of the lower part of the thymic area. Surgical resection revealed an ectopic mediastinal seminoma. The evolution consisted of paraneoplastic fever and crossed-syndrome with right hemiparesia and left common oculomotor nerve paralysis. Treatment was completed by two cycles of carboplatin, corticosteroids and substitutive opotherapy. Paraneoplastic fever disappeared, but behavioral disorders and palsy remain unchanged. The patient died two years later in a bedridden state. This case of paraneoplastic limbic encephalitis associated with positive anti-RI antibodies and mediastinal seminoma is exceptional and has not to our knowledge been described in the literature. Cancers usually associated with anti-RI antibody are breast and lung cancer. Paraneoplastic limbic encephalitis is not the classical clinical presentation, which usually is brainstem encephalitis. Hypothalamic involvement, uncommon in paraneoplastic limbic encephalitis is mainly associated with positive antineuronal anti-Ma2 antibodies. Finally, the gadolinium enhancement on encephalic MRI is unusual in paraneoplastic limbic encephalitis.
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Anticorpos Antineoplásicos/imunologia , Antígenos de Neoplasias/imunologia , Encefalite Límbica/imunologia , Encefalite Límbica/patologia , Proteínas do Tecido Nervoso/imunologia , Proteínas de Ligação a RNA/imunologia , Anticorpos Antineoplásicos/análise , Antígenos de Neoplasias/análise , Biomarcadores , Evolução Fatal , Ginecomastia/etiologia , Humanos , Encefalite Límbica/psicologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/análise , Antígeno Neuro-Oncológico Ventral , Obesidade/etiologia , Oftalmoplegia/etiologia , Paresia/etiologia , Proteínas de Ligação a RNA/análiseRESUMO
BACKGROUND: T-type calcium channels have been shown to play an important role in the initiation and maintenance of neuropathic pain and represent a promising therapeutic target for new analgesic treatments. Ethosuximide (ETX), an anticonvulsant and a T-type channel blocker has shown analgesic effect in several chronic pain models but has not yet been evaluated in patients with neuropathic pain. METHODS: This proof-of-concept, multicentre, double-blind, controlled and randomized trial compared the efficacy and safety of ETX (given as add-on therapy) to an inactive control (IC) in 114 patients with non-diabetic peripheral neuropathic pain. After a 7-day run-in period, eligible patients aged over 18 years were randomly assigned (1:1) to ETX or IC for 6 weeks. The primary outcome was the difference between groups in the pain intensity (% of change from the baseline to end of treatment) assessed in the intention-to-treat population. This study is registered with EudraCT (2013-004801-26) and ClinicalTrials.gov (NCT02100046). RESULTS: The study was stopped during the interim analysis due to the high number of adverse events in the active treatment group. ETX failed to reduce total pain and showed a poor tolerance in comparison to IC. In the per-protocol analysis, ETX significantly reduced pain intensity by 15.6% (95% CI -25.8; -5.4) from baseline compared to IC (-7.8%, 95% CI -14.3; -1.3; p = 0.033), but this result must be interpreted with caution because of a small subgroup of patients. CONCLUSION: Ethosuximide did not reduce the severity of neuropathic pain and induces, at the doses used, many adverse events. SIGNIFICANCE: This article shows that ETX is not effective to treat neuropathic pain. Nevertheless, per-protocol analysis suggests a possible analgesic effect of ETX. Thus, our work adds significant knowledge to preclinical and clinical data on the benefits of T-type calcium channel inhibition for the treatment of neuropathic pain.
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Bloqueadores dos Canais de Cálcio/uso terapêutico , Dor Crônica/tratamento farmacológico , Etossuximida/uso terapêutico , Neuralgia/tratamento farmacológico , Adulto , Idoso , Analgésicos/uso terapêutico , Anticonvulsivantes/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudo de Prova de ConceitoRESUMO
Meningeal involvement is a rare occurrence in Wegener's Granulomatosis (WG). A Medline search uncovered only 48 previously reported cases. Here we describe the clinical features of meningeal involvement in WG and to evaluate the association with systemic disease extension. Through a systematic literature review of papers concerning meningeal involvement in WG, we collected and analysed data about sex, age, disease extension, symptoms, cerebrospinal fluid examination, imaging, ANCA and histology about previously reported patients. Headache is almost always the first symptom of meningeal involvement in WG. Later in the course of the disease other abnormalities may develop. Among them cranial nerve palsy, seizures and encephalopathy are the most frequent. Diagnosis is obtained by neuroimaging, which may disclose two distinct patterns of meningeal thickening: diffuse or focal. 62.9% of patients tests positive for ANCA. Histology typically shows necrotizing granulomatosis. Meningeal involvement is by far more frequent in the setting of localized WG. Meningitis is a rare complication of WG. It usually develops in patients with localized disease who are more likely to have destructive lesions of the upper airways. It may be recognized by a constellation of clinical and radiological findings and by histological signs of necrotizing granulomatosis, with little or no vasculitis.
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Granulomatose com Poliangiite/complicações , Meninges/patologia , Meningite/etiologia , Adulto , Anticorpos Anticitoplasma de Neutrófilos/análise , Doenças dos Nervos Cranianos/etiologia , Doenças dos Nervos Cranianos/patologia , Feminino , Cefaleia/etiologia , Cefaleia/patologia , Humanos , Masculino , Meninges/química , Meninges/diagnóstico por imagem , Meningite/diagnóstico , Meningite/patologia , Pessoa de Meia-Idade , Radiografia , Convulsões/etiologia , Convulsões/patologiaRESUMO
OBJECTIVES: To evaluate the rate of different organs involvement in 50 patients with Wegener's Granulomatosis (GW), and to describe their clinical manifestations and their response to treatment. METHODS: We evaluated 50 consecutive patients with GW, come to our attention from January 1987 to May 2003. 43 patients met the 1990 American College of Rheumatology (ACR) criteria for classification of GW; 7 patients the 1993 ELK criteria. RESULTS: 82% of patients presented Ear/Nose/Throat (ENT) involvement, which is the most common site of inflammation. 22% of our patients had ENT-restricted disease; in 78% of cases disease extended to other organs. Lungs were involved in 72% of cases; kidney in 36%; eye in 24%; nervous system (NS) in 14% (central NS in 10% and peripheral NS in 4%); skin in 10%; heart in 8%; testis in 4%. Arthritis was present in 10% of patients. We discuss treatment of all patients and response to therapy of those 28 whose follow-up is available. CONCLUSIONS: Involvement of airways and kidney is by far the most common in GW, though potentially any other organ or system may be affected. The total rate of other organs involvement is 70%.
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Granulomatose com Poliangiite/complicações , Adolescente , Adulto , Idoso , Criança , Feminino , Granulomatose com Poliangiite/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Takayasu's arteritis (TA) is a chronic inflammatory disease of unknown origin, primarily affecting the walls of large vessels. TA can be a severe and life-threatening disease, and has relevant consequences for the patient's life-style. Mortality and morbidity depend on both the direct effect of the vascular lesions and the following complications. The mainstay of TA therapy is based on the use of glucocorticoids alone or in association with cytotoxic drugs. Unfortunately, in the majority of cases, only a partial control of the disease is obtained. The therapeutic strategy may vary in different countries, and in Japan, where the disease was first described, high dose glucocorticoids are preferred to glucocorticoids in association with cytotoxic agents. We present here a review of the pharmacologic strategies most commonly adopted for the treatment of TA in America, Italy and Japan, together with our experience on 31 TA patients, who have been followed in the last two decades. The discussion is also open on which criteria are more accurate in measuring disease activity.
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Arterite de Takayasu/terapia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Terapia de Imunossupressão , Vigilância da População , Gravidez , Complicações Cardiovasculares na Gravidez/terapiaRESUMO
The association between Systemic Lupus Erythematosus (SLE) and thymoma occurs with a greater frequency than dictated by coincidence alone. The immunologic effects of thymectomy on the appearance and/or the course of SLE are still to be elucidated. We report one case of SLE diagnosed at the same time as thymoma, and two cases of thymoma associated with immunologic disorders in the absence of clinical signs and symptoms diagnostic of SLE.
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Doenças Autoimunes/complicações , Lúpus Eritematoso Sistêmico/complicações , Timoma/complicações , Neoplasias do Timo/complicações , Adulto , Doenças Autoimunes/diagnóstico , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Pessoa de Meia-Idade , Timoma/diagnóstico , Neoplasias do Timo/diagnósticoRESUMO
OBJECTIVE: To verify whether antiphospholipid antibodies (aPL) recognize and opsonize apoptotic human cells. METHODS: Apoptosis was induced via CD95 crosslinking or ultraviolet irradiation. IgG and anti-beta2-glycoprotein I (anti-beta2-GPI) antibodies were purified from patient sera by affinity chromatography. The aPL that bound to apoptotic cells were assessed by flow cytometry, and the subdomains recognized were identified by confocal microscopy. Human macrophages were derived from monocytes, and their ability to phagocytose 3H-labeled apoptotic bodies, whether opsonized or not opsonized by aPL, was assessed. Tumor necrosis factor alpha (TNF alpha) secretion was evaluated by enzyme-linked immunosorbent assay. RESULTS: The aPL, but not control Ig or Ig from aPL-negative patients, bound to apoptotic cells, but not to viable cells. Nuclear antigens were not recognized. Opsonization of apoptotic cells by aPL substantially enhanced recognition and binding by scavenger macrophages, with massive TNF alpha secretion. CONCLUSION: Antiphospholipid antibodies facilitate apoptotic cell clearance by macrophages and trigger TNF alpha release, possibly enhancing the immunogenicity of the autoantigens they contain.
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Anticorpos Antifosfolipídeos/imunologia , Apoptose/fisiologia , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/patologia , Proteínas Opsonizantes/imunologia , Anticorpos Monoclonais/imunologia , Apoptose/efeitos da radiação , Feminino , Humanos , Macrófagos/fisiologia , Masculino , Fator de Necrose Tumoral alfa/metabolismo , Raios Ultravioleta , Receptor fas/imunologiaRESUMO
OBJECTIVE: To verify whether the prototypical long pentraxin PTX3 represents an indicator of the activity of small-vessel vasculitis. METHODS: Concentrations of PTX3, a pentraxin induced in endothelium by cytokines, were measured by enzyme-linked immunosorbent assay in the sera of 43 patients with Churg-Strauss syndrome, Wegener's granulomatosis, and microscopic polyangiitis. PTX3 was also measured in the sera of 28 patients with systemic lupus erythematosus (SLE), 22 with rheumatoid arthritis, and 16 with CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias). Serum concentrations of C-reactive protein (CRP) were measured by immunoturbidimetry. The cells involved in PTX3 production in vivo were identified in skin biopsy samples. RESULTS: Patients with active vasculitis had significantly higher concentrations of PTX3 than did those with quiescent disease (P < 0.001). PTX3 levels in the latter group were similar to those in healthy controls. PTX3 levels were higher in patients with untreated vasculitis and lower in patients who underwent immunosuppressive treatments (P < 0.005). In contrast, patients with active SLE had negligible levels of the pentraxin. PTX3 levels did not correlate with CRP levels in vasculitis patients. Endothelial cells produced PTX3 in active skin lesions. CONCLUSION: PTX3 represents a novel acute-phase reactant produced at sites of active vasculitis.
Assuntos
Proteína C-Reativa/análise , Síndrome de Churg-Strauss/sangue , Granulomatose com Poliangiite/sangue , Componente Amiloide P Sérico/análise , Doença Aguda , Reação de Fase Aguda , Adulto , Idoso , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/imunologia , Biomarcadores , Proteína C-Reativa/metabolismo , Síndrome CREST/sangue , Síndrome CREST/diagnóstico , Síndrome CREST/imunologia , Criança , Síndrome de Churg-Strauss/diagnóstico , Síndrome de Churg-Strauss/imunologia , Endotélio Vascular/química , Endotélio Vascular/imunologia , Endotélio Vascular/metabolismo , Feminino , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/imunologia , Humanos , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Componente Amiloide P Sérico/metabolismoRESUMO
OBJECTIVE: To verify the association of ribosomal anti-P antibodies (anti-P), as detected by a sensitive ELISA, with serological findings and clinical manifestations, including neuropsychiatric involvement evaluated according to the American College of Rheumatology (ACR) nomenclature, in a large cohort of patients with systemic lupus erythematosus (SLE). METHODS: Anti-P were evaluated in the serum of 149 consecutive Italian SLE patients by an ELISA using a multiple antigen peptide carrying four copies of a common P0, P1 and P2 epitope. A complete laboratory evaluation and clinical examination were performed in each patient. In addition, all patients underwent an accurate neuropsychiatric and neuropsychological assessment performed by trained specialists according to the 1999 ACR suggestions. RESULTS: Serum anti-P were detected in 18/149 patients (12.1%). The anti-P prevalence was similar (11.7%) when the analysis was performed in a larger series of sera including 82 additional SLE patients, who were not included in the clinical study. The age of anti-P-positive patients at disease onset was less than 33 yr and, in comparison with the anti-P-negative patients, these patients showed more active disease activity and a higher prevalence of photosensitivity and malar and discoid rash. A strong association between IgG anticardiolipin antibodies and anti-P was also found. However, anti-P were associated with neither neuropsychiatric syndromes nor cognitive impairment. CONCLUSION: This study does not seem to confirm the described association of anti-P with SLE neuropsychiatric manifestations. However, it supports the anti-P association with different skin manifestations as well as the presence of anticardiolipin in a subset of patients with SLE characterized by early disease onset.