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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.
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Prova Pericial , Controle de Infecções/normas , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/terapia , Guias de Prática Clínica como Assunto , Adolescente , Adulto , França , Humanos , Hospedeiro Imunocomprometido , Controle de Infecções/métodos , Infecções/diagnóstico , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Literatura de Revisão como Assunto , Vacinação/normas , Adulto JovemRESUMO
OBJECTIVES: Little data are available regarding the rate and predicting factors of serious infections in patients with rheumatoid arthritis (RA) treated with abatacept (ABA) in daily practice. We therefore addressed this issue using real-life data from the Orencia and Rheumatoid Arthritis (ORA) registry. METHODS: ORA is an independent 5-year prospective registry promoted by the French Society of Rheumatology that includes patients with RA treated with ABA. At baseline, 3 months, 6â months and every 6â months or at disease relapse, during 5â years, standardised information is prospectively collected by trained clinical nurses. A serious infection was defined as an infection occurring during treatment with ABA or during the 3â months following withdrawal of ABA without any initiation of a new biologic and requiring hospitalisation and/or intravenous antibiotics and/or resulting in death. RESULTS: Baseline characteristics and comorbidities: among the 976 patients included with a follow-up of at least 3â months (total follow-up of 1903 patient-years), 78 serious infections occurred in 69 patients (4.1/100 patient-years). Predicting factors of serious infections: on univariate analysis, an older age, history of previous serious or recurrent infections, diabetes and a lower number of previous anti-tumour necrosis factor were associated with a higher risk of serious infections. On multivariate analysis, only age (HR per 10-year increase 1.44, 95% CI 1.17 to 1.76, p=0.001) and history of previous serious or recurrent infections (HR 1.94, 95% CI 1.18 to 3.20, p=0.009) were significantly associated with a higher risk of serious infections. CONCLUSIONS: In common practice, patients treated with ABA had more comorbidities than in clinical trials and serious infections were slightly more frequently observed. In the ORA registry, predictive risk factors of serious infections include age and history of serious infections.
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Abatacepte/efeitos adversos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Imunossupressores/efeitos adversos , Infecções Oportunistas/induzido quimicamente , Abatacepte/uso terapêutico , Adulto , Fatores Etários , Idoso , Antirreumáticos/uso terapêutico , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/imunologia , Comorbidade , Feminino , França/epidemiologia , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/epidemiologia , Infecções Oportunistas/imunologia , Sistema de Registros , Fatores de RiscoRESUMO
OBJECTIVES: To evaluate the prevalence of late-onset neutropenia and its complications in patients treated with rituximab (RTX) for rheumatoid arthritis (RA) and other autoimmune diseases (AIDs) in a prospective registry. METHODS: The AutoImmunity and Rituximab registry is an independent 7-year prospective registry promoted by the French Society of Rheumatology. For each episode of neutropenia, data were validated by the clinician in charge of the patient. RESULTS: Among 2624 patients treated with RTX for refractory AIDs, and at least 1 follow-up visit (a total follow-up of 4179 patient-years in RA and 987 patient-years in AIDs), late-onset neutropenia was observed in 40 patients (25 RA (1.3% of patients with RA, 0.6/100 patient-years), and AIDs in 15 (2.3% of patients with AIDs, 1.5/100 patient-years)). 6 patients (15%) had neutrophils <500/mm(3), 8 (20%) had neutrophils between 500 and 1000/mm(3), and 26 (65%) had neutrophils between 1000 and 1500/mm(3). Neutropenia occurred after a median period of 4.5 (3-6.5) months after the last RTX infusion in patients with RA, and 5 (3-6.5) months in patients with AIDs. 5 patients (12.5%), 4 of them with neutrophils lower than 500/mm(3), developed a non-opportunistic serious infection and required antibiotics and granulocyte colony-stimulating factor injections, with a favourable outcome. After resolution of their RTX-related neutropenia, 19 patients (47.5%) were re-treated, and neutropenia reoccurred in 3 of them. CONCLUSIONS: Late-onset neutropenia might occur after RTX and may result in serious infections. Thus, monitoring of white cell count should be performed after RTX. However, in this large registry of patients with AIDs, the frequency of RTX-induced neutropenia was much lower than that previously reported in patients treated for blood malignancies or AIDs.
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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.
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Doenças Cardiovasculares/etiologia , Lúpus Eritematoso Sistêmico/complicações , Programas de Rastreamento/métodos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/tratamento farmacológico , Medicina Baseada em Evidências , Prova Pericial , Guias como Assunto , Humanos , Fatores de Risco , Prevenção SecundáriaRESUMO
BACKGROUND: Genetic risk factors for sporadic pancreatic cancer are largely unknown but actually under high exposure. Findings of correlations between the AB0 blood group system (Chromosome 9q34,1-q34,2) and the risk of pancreatic cancer (PC) in patients from Asia, America and south Europe have already been published. So far it is unclear, whether this correlation between blood group an PC incidence can be found in German patients as well. METHODS: One hundred and sixty-six patients who underwent a resection of PC were evaluated in a period between 2000 and 2010. Blood group reference distribution for the German population is given as: 0: 41%; A: 43%; B: 11%; AB: 5%; Rhesus positive: 85%; Rhesus negative: 15%. Analyses were done using the non-parametric Chi(2)-test (p-value two sided; SPSS 19.0). RESULTS: Median age was 62 (34-82) years. Gender: female 73/44%; male: 93/56%. Observed blood group proportions: 0: 43 (25.9%)/A: 94 (56.6%)/B: 16 (9.6%)/AB: 13 (7.8%)/Rhesus positive: 131 (78.9%)/negative: 35 (21.1%). We detected a significant difference to the German reference distribution of the AB0 system (Chi(2) 19.34, df 3, p < 0.001). Rhesus factor has no impact on AB0-distribution (Chi(2) 4.13, df 3, p = 0.25), but differs significantly from reference distribution-probably due to initial AB0-variation (Chi(2) 4.82, df 1, p = 0.028). The odds ratio for blood group A is 2.01 and for blood group 0 is 0.5. CONCLUSIONS: The incidence of PC in the German cohort is highly associated with the AB0-system as well. More patients with blood group A suffer from PC (p < 0.001) whereas blood group 0 was less frequent in patients with PC (p < 0.001). Thus, our findings support the results from other non-German surveys. The causal trigger points of this carcinogenesis correlation are still not known.
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BACKGROUND: TNFAIP3 encodes the ubiquitin-modifying enzyme, a key regulator of inflammatory signalling pathways. Convincing associations between TNFAIP3 variants and autoimmune diseases have been reported. OBJECTIVE: To investigate the association of TNFAIP3 polymorphisms with systemic sclerosis (SSc). METHODS: Three single nucleotide polymorphisms (SNPs) in a set of 1018 patients with SSc and 1012 controls of French Caucasian origin were genotyped. Two intergenic SNPs, rs10499194 and rs6920220, and one located in TNFAIP3 intron 2, rs5029939, were selected. The TNFAIP3 rs5029939 found to be associated with SSc in this first set was then genotyped in a second set of 465 patients with SSc and 182 controls from Germany and 184 patients with SSc and 124 controls from Italy. Pooled odd ratios were calculated by Mantel-Haenszel meta-analysis. RESULTS: The rs5029939 G allele was found to be significantly associated with SSc susceptibility (pooled OR=2.08 (95% CI 1.59 to 2.72); p=1.16×10â»7), whereas the rs10499194 and rs6920220 variants displayed no association. Only one of the predicted haplotypes investigated in the French sample was significantly associated with SSc (p=8.91×10â»8), and this haplotype was discriminating only in the presence of the rs5029939 risk allele, suggesting that this SNP tags the association signal. The strongest associations of rs5029939 with subphenotypes, having large magnitudes for complex genetic disorders, were observed for diffuse cutaneous SSc (pooled OR=2.71 (1.94 to 3.79), p=5.2×10â»9), fibrosing alveolitis (pooled OR=2.26 (1.61 to 3.17), p=2.5×10â»6) and pulmonary arterial hypertension (pooled OR=3.11 (1.86 to 5.17), p=1.3×10â»5). CONCLUSION: These results suggest that TNFAIP3 is a genetic susceptibility factor for SSc.
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Doenças Autoimunes/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas Nucleares/genética , Polimorfismo de Nucleotídeo Único , Escleroderma Sistêmico/genética , Adulto , Idoso , Estudos de Casos e Controles , Proteínas de Ligação a DNA , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Proteína 3 Induzida por Fator de Necrose Tumoral alfaRESUMO
INTRODUCTION: There are insufficient data regarding the efficacy and safety of vaccination in patients with auto-immune disease (AID) and/or drug-related immune deficiency (DRID). The objective of this study was to obtain professional agreement on vaccine practices in these patients. METHODS: A Delphi survey was carried out with physicians recognised for their expertise in vaccinology and/or the caring for adult patients with AID and/or DRID. For each proposed vaccination practice, the experts' opinion and level of agreement were evaluated. RESULTS: The proposals relating to patients with AID specified: the absence of risk of AID relapse following vaccination; the possibility of administering live virus vaccines (LVV) to patients not receiving immunosuppressants; the pertinence of determining protective antibody titre before vaccination; the absence of need for specific monitoring following the vaccination. The proposals relating to patients with DRID specified that a 3-6 month delay is needed between the end of these treatments and the vaccination with LVV. There is no contraindication to administering LVV in patients receiving systemic corticosteroids prescribed for less than two weeks, regardless of their dose, or at a daily dose not exceeding 10mg of prednisone, if this involves prolonged treatment. Out of 14 proposals, the level of agreement between the experts was "very good" for eleven, and "good" for the remaining three. CONCLUSION: Proposals for vaccine practices in patients with AID and/or DRID should aid with decision-making in daily medical practice and provide better vaccine coverage for these patients.
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Doenças Autoimunes/imunologia , Doenças Autoimunes/terapia , Síndromes de Imunodeficiência/imunologia , Síndromes de Imunodeficiência/terapia , Vacinação/efeitos adversos , Vacinação/métodos , Corticosteroides/efeitos adversos , Adulto , Antineoplásicos/efeitos adversos , Prova Pericial , Humanos , Síndromes de Imunodeficiência/induzido quimicamente , Terapia de Imunossupressão/efeitos adversos , Imunossupressores/efeitos adversos , Inquéritos e Questionários , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Vacinação/estatística & dados numéricosRESUMO
OBJECTIVE: The aetiology of SAPHO (synovitis, acne, palmoplantar pustulosis, hyperostosis, osteitis) syndrome seems to involve genetic, infectious and immunological components. We examined innate and adaptive immune responses in SAPHO syndrome, as compared with PsA and RA. We also studied the effect of etanercept on immunological parameters. METHODS: We studied 29 patients with SAPHO syndrome, as well as 22 patients with RA, 21 patients with PsA and 15 healthy controls. Adaptive immune responses were investigated by assaying total serum immunoglobulins and several autoantibodies. Innate immunity was studied by quantifying blood PMN functions and plasma cytokine levels. PMN responses to Propionibacterium acnes were tested ex vivo. Eight patients who received etanercept for refractory rheumatic disorders were tested before and after 28 days of treatment. RESULTS: SAPHO syndrome was associated with elevated IL-8 and IL-18 plasma levels. IL-8 and TNF-alpha production by purified PMN was higher in the three patient groups than in the healthy controls, but the oxidative burst and IL-18 production were normal. No autoantibodies were detected in SAPHO patients. Induction of PMN IL-8 and TNF-alpha production by P. acnes was impaired in the SAPHO group as compared with the RA and PsA groups. After 28 days of etanercept therapy, PMN IL-8 and TNF-alpha production was down-regulated and TNF-alpha plasma levels were increased. CONCLUSIONS: These results support the view that the SAPHO syndrome may be triggered by an infectious state involving P. acnes, contributing to the strong humoral and cellular pro-inflammatory responses. Etanercept modulation of PMN activation status emphasizes these new immunological findings.
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Síndrome de Hiperostose Adquirida/imunologia , Síndrome de Hiperostose Adquirida/tratamento farmacológico , Adulto , Idoso , Antígenos de Bactérias/imunologia , Antirreumáticos/uso terapêutico , Autoanticorpos/sangue , Proteína C-Reativa/análise , Células Cultivadas , Citocinas/sangue , Etanercepte , Feminino , Humanos , Imunoglobulina G/uso terapêutico , Imunoglobulinas/sangue , Interleucina-18/biossíntese , Interleucina-8/biossíntese , Masculino , Pessoa de Meia-Idade , Neutrófilos/imunologia , Propionibacterium acnes/imunologia , Espécies Reativas de Oxigênio/metabolismo , Receptores do Fator de Necrose Tumoral/uso terapêutico , Acetato de Tetradecanoilforbol/imunologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/biossínteseRESUMO
OBJECTIVE: To evaluate predictors of pulmonary arterial hypertension (PAH) in a prospective cohort of patients with systemic sclerosis (SSc). METHODS: Routine clinical assessments as well as measurements of the diffusing capacity for carbon monoxide/alveolar volume (DLCO/VA) ratio and N-terminal pro-brain natriuretic peptide (NT-proBNP) level were performed in a prospective cohort of 101 SSc patients who did not have PAH or severe comorbidities. After a planned 36-month followup, we evaluated the predictive value of these parameters for the development of precapillary PAH, as demonstrated by cardiac catheterization, disease progression, and death. Criteria for cardiac catheterization were a systolic pulmonary artery pressure (PAP) of >40 mm Hg on echocardiography, a DLCO value of <50% without pulmonary fibrosis, and unexplained dyspnea. RESULTS: Eight patients developed PAH, 29 had disease progression, and 10 died during a median followup of 29 months. Kaplan-Meier analysis identified the following baseline parameters as being predictors of PAH: DLCO/VA ratio <70% or <60% (P<0.01 for each comparison), elevated plasma NT-proBNP level (>97th percentile of normal; P = 0.005), echocardiographically estimated systolic PAP >40 mm Hg (P=0.08), and erythrocyte sedimentation rate >28 mm/hour (P=0.015). In multivariate analyses, an elevated baseline NT-proBNP level (hazard ratio [HR] 9.97 [95% confidence interval (95% CI) 1.69-62.42]) and a DLCO/VA ratio <60% (HR 36.66 [95% CI 3.45-387.6]) were predictors of the occurrence of PAH during followup. An increased NT-proBNP level together with a decreased DLCO/VA ratio of <70% was highly predictive of the occurrence of PAH during followup (HR 47.20 [95% CI 4.90-450.33]). CONCLUSION: This prospective study identified a decreased DLCO/VA ratio and an increased NT-proBNP as predictors of PAH in SSc. Use of these markers should result in improved PAH risk stratification and allow earlier initiation of therapy.
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Monóxido de Carbono/sangue , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/mortalidade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Escleroderma Sistêmico/metabolismo , Escleroderma Sistêmico/mortalidade , Adulto , Idoso , Biomarcadores/sangue , Capilares , Comorbidade , Difusão , Progressão da Doença , Feminino , Seguimentos , Humanos , Hipertensão Pulmonar/diagnóstico , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
Intravenous (IV) administration of anti-D in patients with autoimmune thrombocytopenia (AITP) may result in severe hemolysis and even death. Over a 3-year period, we gave anti-D only subcutaneously (SC), and none of our patients have developed any acute adverse reaction. Most importantly, SC delivery of anti-D produces largely the same beneficial effect as obtained by IV anti-D. We recommend replacement of IV administration of anti-D by SC administration in AITP.
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Isoanticorpos/administração & dosagem , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Adulto , Criança , Feminino , Hemorragia/tratamento farmacológico , Hemorragia/etiologia , Hemorragia/prevenção & controle , Humanos , Injeções Intravenosas , Injeções Subcutâneas , Masculino , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/complicações , Imunoglobulina rho(D) , Resultado do TratamentoRESUMO
Six dose groups of 8 male and female rats respectively received a daily dose equivalent to 0, 0.15, 0.006, 0.03, 0.15 or 0.3 mg/kg b.w./day chlorpyrifos (groups 1-6) and the last four dose groups (groups 3-6) received in addition daily doses equivalent to 18 mg/kg b.w./day alphacypermethrin, 30 mg/kg b.w./day bromopropylate, 45 mg/kg b.w./day carbendazim and 12.5 mg/kg b.w./day mancozeb for 28 days. Plasma acetylcholinesterase was significantly decreased in the groups 2, 5 and 6 males. Total white blood cell count was significantly lower in females of group 6. Total red blood cell count, haematocrite and haemoglobin concentration was significantly reduced in both male and female rats of groups 5 and 6. Relative liver weight was significantly increased in groups 3-6 male and female rats. Absolute thyroid gland weight was significantly increased in groups 3, 5 and 6 male rats and of groups 3-6 female rats, and relative thyroid gland weight was significantly increased in groups 2-6 male rats and of groups 3-6 female rats. Absolute thymus weight of groups 3-6 male and female rats and relative thymus weight of groups 3-6 male rats and groups 3 and 4 female rats was significantly decreased. A mild degree of centrilobular cell hypertrophy of the liver was seen in all male rats and of three female rats of group 6. In the thyroid gland follicular cell hypertrophy was present in one female in the control group and in six females and seven males of group 6. It was concluded that inhibition of acetylcholinesterase activity in plasma and brain by chlorpyrifos was not enhanced by co-administration of the other four pesticides. Effects were seen in liver, thyroid, thymus and blood in the combination groups. However, identification of the pesticide(s) responsible for these changes would require further studies of the individually pesticides as well as various combinations of the pesticides.
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Misturas Complexas/toxicidade , Contaminação de Alimentos/análise , Resíduos de Praguicidas/toxicidade , Praguicidas/toxicidade , Acetilcolinesterase/sangue , Acetilcolinesterase/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Contagem de Células Sanguíneas , Encéfalo/enzimologia , Clorpirifos/farmacocinética , Clorpirifos/toxicidade , Inibidores da Colinesterase/farmacocinética , Inibidores da Colinesterase/toxicidade , Misturas Complexas/farmacocinética , Dieta , Relação Dose-Resposta a Droga , Interações Medicamentosas , Feminino , Inseticidas/farmacocinética , Inseticidas/toxicidade , Fígado/metabolismo , Masculino , Proteínas do Tecido Nervoso/metabolismo , Nível de Efeito Adverso não Observado , Tamanho do Órgão/efeitos dos fármacos , Resíduos de Praguicidas/farmacocinética , Praguicidas/farmacocinética , Ratos , Aumento de Peso/efeitos dos fármacosRESUMO
Among connective tissue diseases, systemic lupus erythematosus is the illness that is most concerned by hormonal life events. The sex ratio is 9/1, and symptoms begin mostly during the third decade, sometimes during birth pill contraception or during pregnancy. As soon as systemic lupus is under control of an efficient treatment, pregnancy is no longer contra-indicated. A medical multidisciplinary surveillance is required. Complicated pregnancy concerns mother and baby. Lupus flares are more frequent during the second and third trimesters as well as during the post-partum period. Usually the intensity is moderate. Severe flares concern patients with renal involvement, hypertension and renal insufficiency and are mostly seen in patients with unplanified pregnancy and yet with still active lupus. Foetal death occurs in 10-30% of the cases, depending on the lupus activity and severity (renal lupus). Prematurity remains an important cause of morbidity (30% of live births). Foetal deaths and prematurity are even more frequent if the patient has an antiphospholipid syndrome. Neonatal cutaneous lupus and auriculo-ventricular congenital heart block is infrequent (1% of SLE patients with anti-Ro/SSA antibodies). Among other connective tissue diseases, polymyositis has a very severe obstetrical prognosis for both mother and foetus. Among primary vasculitis, polyarteritis nodosa, as found during pregnancy, can herald a very bad prognosis.
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Doenças do Tecido Conjuntivo , Hormônios , Lúpus Eritematoso Sistêmico , Complicações na Gravidez , Animais , Síndrome Antifosfolipídica , Anticoncepcionais Femininos , Terapia de Reposição de Estrogênios , Feminino , Morte Fetal , Humanos , Menopausa , Gravidez , Escleroderma SistêmicoRESUMO
INTRODUCTION: Langerhans'cell histiocytosis is a rare and mainly pediatric disease. Patients with hepatic involvement usually have a disseminated form of the disease, with poor prognosis. Sclerosing cholangitis can occur in 10 to 15% of multivisceral Langerhans'cell histiocytosis. We report the case of a 56-years-old patient who developed sclerosing cholangitis 12 years after the diagnosis of Langerhans'cell histiocytosis. EXEGESIS: A 56-years-old man was admitted because of rapid general health impairment with epigastric pain. He was diagnosed as having Langerhans'cell histiocytosis 12 years ago because of a diabetes insipidus. Lungs were involved and during follow-up vertebral osteocondensation also developed. However, Langerhans'cell histiocytosis was clinically silent at the time of admission, without any treatment. Biologically, cholestasis and inflammation were noted. Digestive radiological investigations (echo-endoscopy, CT-scan, MRI) showed homogenous hepatomegaly and a diffuse infiltration of intra and extrahepatic bile ducts. Liver biopsy yielded the diagnosis of sclerosing cholangitis. Clinical and biological improvement occurred with oral corticosteroids (at 12 months after sclerosing cholangitis diagnosis). CONCLUSION: Sclerosing cholangitis is a potential complication of Langerhans'cell histiocytosis, mainly in its multivisceral form. It can occur at a median of 2 years after diagnosis in children, but occasionally much later in adults, whereas Langerhans'cell histiocytosis seems quiescent. Diagnosis is supported by radiological investigations and liver biopsy. As no drug therapy appears clearly effective, liver transplantation must frequently be considered in these patients.
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Colangite Esclerosante/diagnóstico , Colangite Esclerosante/etiologia , Histiocitose de Células de Langerhans/complicações , Dor Abdominal/etiologia , Fatores Etários , Anti-Inflamatórios/uso terapêutico , Biópsia por Agulha , Colagogos e Coleréticos/uso terapêutico , Colangiopancreatografia Retrógrada Endoscópica , Colangite Esclerosante/tratamento farmacológico , Diabetes Insípido/etiologia , Progressão da Doença , Quimioterapia Combinada , Endossonografia , Histiocitose de Células de Langerhans/diagnóstico , Histiocitose de Células de Langerhans/tratamento farmacológico , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Prognóstico , Doenças Raras , Fatores de Tempo , Tomografia Computadorizada por Raios X , Ácido Ursodesoxicólico/uso terapêutico , Redução de PesoRESUMO
Determination and therapy of the underlying pathology in chronic pain syndrome in the lumbar spine is frequently difficult. Minimally invasive and microsurgical techniques may offer advantages. Epiduroscopy is available for visualization of the lumbar epidural space. 93 patients with chronic back-leg pain syndrome were epiduroscopically operated. When findings were appropriate, mechanical instruments and the holmium:YAG laser were applied therapeutically. 45.9 % of these patients presented with positive results in postoperative examination. Pathomorphological processes corresponding to the multifactorial pain processes, which escape detection in modern imaging procedures, can be diagnosed in the epidural space using epiduroscopy Therapeutic intervention is basically possible. However, use is limited due to technical difficulties. Navigation of the endoscope is especially limited in access via the hiatus sacralis.
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Endoscopia , Espaço Epidural/patologia , Espaço Epidural/cirurgia , Terapia a Laser , Perna (Membro)/patologia , Perna (Membro)/cirurgia , Dor Lombar/patologia , Dor Lombar/cirurgia , Vértebras Lombares/patologia , Vértebras Lombares/cirurgia , Dor/patologia , Dor/cirurgia , Adulto , Idoso , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome , Resultado do TratamentoRESUMO
Anti-TNF-alpha therapies are promising new strategies in the treatment of rheumatoid arthritis (RA). Despite good clinical efficacy and tolerance, the possible occurrence of drug-induced autoimmune disorders remains a matter of concern. Induction of antinuclear (ANA) and anti-DNA antibodies is observed in some patients treated with TNF-alpha inhibitors (anti- TNF-alpha antibodies) or soluble TNF-alpha receptor. Of concern is the possibility of induction of true lupus erythematosus by TNF blockers. Few cases without major organ involvement were reported to be associated with infliximab treatment that resolved after anti-TNF discontinuation. Only four cases have been described with the use of etanercept. We report a new case of infliximab-induced lupus syndrome and two new cases of etanercept-induced lupus syndrome in three patients with RA, all of whom had previous isolated positive ANA.
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Anticorpos Monoclonais/efeitos adversos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Imunoglobulina G/efeitos adversos , Lúpus Eritematoso Sistêmico/induzido quimicamente , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Etanercepte , Feminino , Humanos , Infliximab , Lúpus Eritematoso Sistêmico/patologia , Masculino , Pessoa de Meia-Idade , Receptores do Fator de Necrose TumoralRESUMO
OBJECTIVE: To study the value of antibodies to citrullinated proteins/peptides for predicting joint outcomes in patients with recent onset rheumatoid arthritis (RA). METHODS: 191 patients with RA onset within the past year were followed up prospectively for five years. Serum samples obtained from 145 patients at baseline before disease modifying antirheumatic drug treatment were examined using three anticitrullinated protein/peptide antibody assays: antiperinuclear factor (APF) by indirect immunofluorescence (IIF), antikeratin antibodies (AKA) by IIF, and anti-cyclic citrullinated peptide (CCP) antibodies by enzyme linked immunosorbent assay (ELISA). Radiographs of the hands and feet taken at baseline and after three and five years were evaluated using Sharp scores modified by van der Heijde. RESULTS: Anti-CCP ELISA was positive in 58.9% of patients. APF/anti-CCP agreement was 77%. The likelihood of a total Sharp score increase after five years was significantly greater among patients with anti-CCP antibodies (67%; odds ratio (OR) 2.5; 95% confidence interval (95% CI) 1.2 to 5.0) or APF (57%; OR 2.4; 95% CI 1.2 to 4.9) but not rheumatoid factor (RF; OR 0.7; 95% CI 0.3 to 1.5). Mean values for radiographic damage, erosion, and joint narrowing scores at the three times were significantly higher in patients with anti-CCP or APF than in those without. AKA did not significantly predict radiographic damage. In separate analyses of patients with and without RF, anti-CCP or APF was better than RF for predicting total joint damage and joint damage progression after five years. CONCLUSION: Antibodies to citrullinated proteins/peptides determined early in the course of RA by APF IIF or anti-CCP ELISA are good predictors of radiographic joint damage. Further studies of clinical, laboratory, and genetic parameters are needed to improve RA outcome prediction in clinical practice.
Assuntos
Artrite Reumatoide/imunologia , Autoanticorpos/sangue , Citrulina/imunologia , Adulto , Idoso , Anticorpos Antinucleares/sangue , Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Biomarcadores/sangue , Progressão da Doença , Feminino , Seguimentos , Humanos , Queratinas/imunologia , Masculino , Pessoa de Meia-Idade , Peptídeos/imunologia , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Radiografia , Sensibilidade e Especificidade , Índice de Gravidade de DoençaAssuntos
Carcinógenos/toxicidade , Neoplasias Colorretais/induzido quimicamente , Sacarose Alimentar/efeitos adversos , Neoplasias Hepáticas/induzido quimicamente , Lesões Pré-Cancerosas/induzido quimicamente , Quinolinas/toxicidade , Animais , Carcinógenos/administração & dosagem , Neoplasias Colorretais/patologia , Sacarose Alimentar/administração & dosagem , Modelos Animais de Doenças , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/patologia , Masculino , Lesões Pré-Cancerosas/patologia , Quinolinas/administração & dosagem , Distribuição Aleatória , Ratos , Ratos Endogâmicos F344 , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/patologia , Fatores de TempoAssuntos
Colo/efeitos dos fármacos , Neoplasias do Colo/induzido quimicamente , Dextrinas/farmacologia , Sacarose Alimentar/farmacologia , Lesões Pré-Cancerosas/induzido quimicamente , Animais , Azoximetano , Carcinógenos , Divisão Celular/efeitos dos fármacos , Transformação Celular Neoplásica , Colo/enzimologia , Neoplasias do Colo/patologia , Dieta , Masculino , Malondialdeído/análise , Oxirredução , Lesões Pré-Cancerosas/patologia , Distribuição Aleatória , Ratos , Ratos Endogâmicos F344 , Amido/farmacologiaRESUMO
OBJECTIVE: Minimally invasive and endoscopic techniques offer advantages in the treatment of chronic back pain syndrome and may provide for expanded indications and visualization. Epiduroscopy for the visualization of the epidural space still is burdened with technical problems. The mechanical instruments now available, coupled with the narrow working canal, result in marked limitations. The aim of this study was to assess the possibilities and technical requisites for the use of the holmium:YAG laser in lumbar epiduroscopy. BACKGROUND DATA: Epiduroscopy has been used for visualization of the lumbar epidural space since the 1930s. Studies have been performed to evaluate the effects and possibilities of epiduroscopy in chronic back pain. Most of them only describe the anatomical aspects. MATERIALS AND METHODS: Forty-seven patients were epiduroscopied and treated, for findings of corresponding epidural adhesions, with the holmium:YAG laser. The examinations concentrated on the general applicability of the holmium:YAG laser in epiduroscopy and the technical parameters necessary for this procedure. The clinical evaluation of therapy was made prospectively in comparison with the preoperative status and compared to already recorded groups in previous studies. RESULTS: Bending behavior without negative impact of the epiduroscope was only attained with laser fibers less than 300 microm, so a fiber with a diameter of 265 microm was used as the standard. The minimum energy output of the laser required for an adequate ablative effect was 0.8 J at a frequency of 8 Hz. The total energy output was 0.256-1.4 kJ. Complications did not occur intraoperatively nor following the procedure. The follow-up examinations showed no deterioration of the complaints in any patient. There was no occurrence of relevant laser-related edemas or adhesions. The proportion of painful conditions that could be positively influenced corresponded to that in a control group treated only by mechanical means. CONCLUSION: The results show that the holmium:YAG laser considerably expands therapeutic possibilities and aids in solving the technical problems of epiduroscopy. No negative effects occurred when the laser is used.
Assuntos
Dor nas Costas/cirurgia , Endoscopia/métodos , Espaço Epidural , Terapia a Laser/métodos , Adulto , Idoso , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Aderências Teciduais/cirurgiaRESUMO
AIM: Scars in the epidural space play an important role in the chronic lumbar pain syndrome of patients with previous surgical treatment. The results of surgical resection are frequently unsatisfactory. Discrepancies to imaging diagnostics are conspicuous. These are known from experience with endoscopic operations. Minimal adhesions may promote pain. Epiduroscopy is available for visualization of the epidural space. The objective of this study was to examine its possibilities in patients with previous surgical treatment. METHOD: 31 patients with chronic lumbar pain syndrome who had previously received surgical treatment were operated epiduroscopically. Mechanical instruments and the holmium:YAG laser were used for epidural adhesion. RESULTS: All patients showed adhesions. 24 patients also presented with adhesions on the contralateral side. There were marked discrepancies between imaging and intraoperative findings. The use of mechanical instruments was limited. The use of laser fibers resulted in greater possibilities. Back pain could be better influenced than leg pain. The procedure was limited by still-existing technical problems. CONCLUSION: Epiduroscopy offers a novel view of this compartment. Minimal adhesions which are not visible in imaging ean promote pain. They can be partially diagnosed and treated by epiduroscopy. There are still marked limitations to epiduroscopy due to technical problems. These must be minimized.