RESUMEN
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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Testimonio de Experto , Control de Infecciones/normas , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/terapia , Guías de Práctica Clínica como Asunto , Adolescente , Adulto , Francia , Humanos , Huésped Inmunocomprometido , Control de Infecciones/métodos , Infecciones/diagnóstico , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/inmunología , Literatura de Revisión como Asunto , Vacunación/normas , Adulto JovenRESUMEN
OBJECTIVES: Benefits of hydroxychloroquine (HCQ) use on physician reported outcomes are well documented in systemic lupus erythematosus (SLE). We assess for the first time the association and predictive value of blood HCQ levels towards health-related quality of life (HRQOL) in SLE. METHODS: Data from the PLUS study (a randomized, double-blind, placebo-controlled, multicentre study) were utilized. Blood HCQ levels were quantified by high-performance liquid chromatography along with HRQOL assessments (Medical Outcomes Study-SF-36) at baseline (V1) and month 7 (V2). RESULTS: 166 SLE patients' data were analysed. Mean (SD) age and disease duration were 44.4 (10.7) and 9.3 (6.8) years. Eighty-seven per cent were women. Mean (SD, median, IQR) HCQ concentrations in the blood at V1 were 660 (314, 615, 424) ng/ml and increased to 1020 (632, 906, 781) ng/ml at V2 (mean difference 366 units, 95% confidence interval -472 to -260, p < 0.001). No significant correlations between HCQ concentrations with HRQOL domains at V1 or V2 were noted. There were no differences in HRQOL stratified by HCQ concentrations. HCQ concentrations at V1 or changes in HCQ concentration (V2-V1) were not predictive of HRQOL at V2 or changes in HRQOL (V2-V1). CONCLUSIONS: No association of HCQ concentrations with current or longitudinal HRQOL were found in SLE.
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Antirreumáticos/sangre , Hidroxicloroquina/sangre , Lupus Eritematoso Sistémico/sangre , Calidad de Vida , Adulto , Método Doble Ciego , Femenino , Francia , Humanos , Modelos Lineales , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: Blood concentrations of hydroxychloroquine (HCQ) vary widely among patients with systemic lupus erythematosus (SLE). A pharmacokinetic/pharmacodynamic relationship has been found in different situations, and a very low blood concentration of HCQ is a simple marker of nonadherence to treatment. Therefore, interest in blood HCQ concentration measurement has increased, but little is known about factors that influence blood HCQ concentration variability. This study was undertaken to analyze determinants of blood HCQ concentrations. METHODS: We conducted a retrospective analysis of patient data, including data from the Plaquenil Lupus Systemic (PLUS) study, to determine the association of epidemiologic, clinical, and biologic factors with blood HCQ concentrations. Data for nonadherent patients (blood HCQ concentration <200 ng/ml) were excluded. RESULTS: To examine homogeneous pharmacologic data, we restricted the analyses of the PLUS data to the 509 SLE patients receiving 400 mg/day. We found no association of ethnicity or smoking with blood HCQ concentrations and no pharmacokinetic drug-drug interaction with antacids or with inhibitors or inducers of cytochrome P450 enzymes. On multivariate analysis, high body mass index (P = 0.008), no treatment with corticosteroids (P = 0.04), increased time between the last tablet intake and measurement of blood HCQ concentrations (P = 0.017), low platelet count (P < 0.001), low neutrophil count (P < 0.001), and high estimated creatinine clearance (P < 0.001) were associated with low blood HCQ concentrations. In 22 SLE patients with chronic renal insufficiency (median serum creatinine clearance 52 ml/minute [range 23-58 ml/minute]) who received 400 mg/day HCQ, the median blood HCQ concentration was significantly higher than that in the 509 patients from the PLUS study (1,338 ng/ml [range 504-2,229 ng/ml] versus 917 ng/ml [range 208-3316 ng/ml]) (P < 0.001). CONCLUSION: We provide a comprehensive analysis of determinants of blood HCQ concentrations. Because this measurement is increasingly being used, these data might be useful for clinicians.
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Corticoesteroides/uso terapéutico , Antirreumáticos/farmacocinética , Hidroxicloroquina/farmacocinética , Lupus Eritematoso Sistémico/tratamiento farmacológico , Adulto , Antirreumáticos/sangre , Antirreumáticos/uso terapéutico , Índice de Masa Corporal , Creatinina/sangre , Femenino , Humanos , Hidroxicloroquina/sangre , Hidroxicloroquina/uso terapéutico , Recuento de Leucocitos , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/complicaciones , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neutrófilos/citología , Obesidad/complicaciones , Insuficiencia Renal Crónica/complicaciones , Estudios Retrospectivos , Trombocitopenia , Factores de Tiempo , Adulto JovenRESUMEN
PURPOSE: Cryofibrinogenemia is an unknown disorder and studies dedicated to it are limited. The aim of our study was to report on the incidence, clinical manifestations and associated diseases in patients with isolated cryofibrinogenemia. METHODS: This is a retrospective single-center study. Patients included in this study had a positive and isolated detection of cryofibrinogen between January 1st, 2011 and December 31st, 2012. Identification was possible through the database of the laboratory of immunology. RESULTS: Two hundred and eighty-one consecutive orders of cryofibrinogenemia were identified. Seventy-three patients had a positive detection of cryofibrinogenemia. Among them, 12 had an isolated cryofibrinogenemia and sixty-one patients (84%) had concomitant cryofibrinogenemia and cryoglobulinemia. The mean age was 59±19years. Seven patients were female (58%). Cutaneous manifestations were present in half case. Peripheral nerve involvement was present in 5 cases (42%) and rheumatic manifestations in 4 patients (33%). A thrombotic event was reported in 7 patients (58%). Renal impairment was present in 7 patients. The median cryofibrinogen concentration was 254±304mg/L. Five patients had a secondary cryofibrinogenemia. The most often prescribed treatment was corticosteroids. CONCLUSION: Cryofibrinogenemia is an unknown disorder. Testing for cryoglobulinemia is more frequent than for cryofibrinogenemia whereas clinical manifestations are similar. Detection of cryofibrinogen is positive in most of the cases, with an important prevalence of thrombotic events in this population. This study confirms the importance of conducting prospective studies on cryofibrinogenemia.
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Crioglobulinemia , Crioglobulinemia/diagnóstico , Femenino , Francia , Hospitales Universitarios , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
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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Enfermedades Cardiovasculares/etiología , Lupus Eritematoso Sistémico/complicaciones , Tamizaje Masivo/métodos , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/tratamiento farmacológico , Medicina Basada en la Evidencia , Testimonio de Experto , Guías como Asunto , Humanos , Factores de Riesgo , Prevención SecundariaRESUMEN
PURPOSE: To evaluate in France the annual direct medical cost of adult patients with active systemic lupus erythematosus (SLE) on medication and estimate the cost of a flare. METHODS: A two-year, observational, retrospective, multicenter study, carried out between December 2010 and February 2011. Patients' characteristics, SLE disease activity and severity, rate of flares, healthcare consumption (medications, hospitalisations, etc.) were evaluated. Medical costs were assessed from the national Health Insurance perspective. Cost predictors were estimated using multivariate regression models. RESULTS: Eight centres specialized in SLE management included 93 eligible patients (including 50.5% severe). The mean age was 39.9 (11.9) years and 93.5% were women. At baseline, the mean SLE duration was 9.8 (6.6) years. The mean scores of the SELENA-SLEDAI instrument and the SLICC/ACR index were higher in severe patients (9.8 vs 5.6, and 1.2 vs 0.4 respectively; P<0.001). Over the study period, 51% of patients received the combination containing at least corticosteroids or immunosuppressants. The mean annual direct medical cost of severe patients was 4660 versus 3560 for non-severe patients (non-significant difference). The cost of medications (61.8% of the annual cost) was higher in severe patients (3214 vs 1856; P<0.05). Immunosuppressants and biologics represented 26.5% and 4.6% of the annual total cost respectively. Patients experienced on average 1.10 (0.59) flares/year, of which 0.50 were severe flare. The occurrence of a new severe flare incremented the annual cost of 1330 (P<0.05). CONCLUSION: Medications represented the major component of the annual direct medical cost. Severe flares increase significantly the cost of SLE care management.
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Lupus Eritematoso Sistémico/economía , Lupus Eritematoso Sistémico/epidemiología , Adulto , Productos Biológicos/economía , Productos Biológicos/uso terapéutico , Femenino , Francia/epidemiología , Glucocorticoides/economía , Glucocorticoides/uso terapéutico , Servicios de Salud/estadística & datos numéricos , Hospitalización/economía , Hospitalización/estadística & datos numéricos , Humanos , Inmunosupresores/economía , Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/terapia , Masculino , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
The objective of this study was to characterize the condensed tannins (CTs) in wrapped silage bales of sainfoin (Onobrychis viciifolia) and examine their potential action on in vivo and in situ digestive characteristics in sheep. Silage was made from sainfoin, cut at two phenological stages. The first phenological stage, at which silage was made, was from the first vegetation cycle at the end of flowering and the second stage silage was made from regrowth, 5 weeks after the first cut, but before flowering. The silages made from the two phenological stages were fed to 12 rumen-fistulated sheep in a crossover design. Of the 12 sheep, six received polyethylene glycol (PEG) to bind with and remove the effects of CT, whereas the other six were dosed with water. Organic matter digestibility, total-tract N digestibility and N (N) balance were measured over 6 days. Kinetic studies were performed on total N, ammonia N (NH3-N) and volatile fatty acids (VFAs) in rumen fluid before and 1.5, 3 and 6 h after feeding. The kinetics of degradation of dry matter and N from Dacron bags suspended in the rumen were also determined. Biological activity of CT (protein-binding capacity) and CT concentration were greater for the silage made from sainfoin at the early flowering stage. Total-tract N digestibility was increased by the addition of PEG (P < 0.001) to the sainfoin silage before flowering (P < 0.001). CTs decreased N excretion in urine (P < 0.05) and increased faecal N excretion (P < 0.001), but had no effect on body N retention, which is beneficial for the animal. Ruminal N degradability was smaller in the presence of active CT (P < 0.001) at both phenological stages; however, soluble N (P = 0.2060) and NH3-N (P = 0.5225) concentrations in rumen fluid remained unchanged. The results of this experiment indicate that CT in the sainfoin retain their ability to affect the nutritive value of preserved forage legumes.
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Digestión/fisiología , Fabaceae/química , Proantocianidinas/farmacología , Ovinos/fisiología , Ensilaje/análisis , Animales , Estudios Cruzados , Digestión/efectos de los fármacos , Ácidos Grasos Volátiles/análisis , Masculino , Nitrógeno/análisis , Nitrógeno/orina , Polietilenglicoles , Proantocianidinas/química , Rumen/química , Rumen/metabolismoRESUMEN
BACKGROUND: Results of uncontrolled studies have suggested that infliximab is efficacious against systemic necrotising vasculitides (SNV) refractory to conventional treatment. However, its safety and ability to induce and maintain remission over the long term remain unknown. OBJECTIVES: To report the use of infliximab to treat refractory SNV, focusing on patients' longer-term outcomes. METHODS: The medical charts of patients given adjunctive infliximab for refractory SNV >/=2 years before this evaluation were reviewed retrospectively. RESULTS: The 15 patients (median age 46 (range 20-69) years, median follow-up 35 (24-41) months) included 10 with Wegener's granulomatosis, 1 microscopic polyangiitis, 3 rheumatoid arthritis-associated and 1 cryoglobulinaemia-related vasculitides. Infliximab was taken for a median time of 8 (2-31) months; 2 patients are still being treated. By day 45, 11 patients had entered remission (Birmingham Vasculitis Activity Score (BVAS) = 0) and 4 others had responded (BVAS decrease >/=50%). Five patients achieved sustained remissions (>/=6 months, corticosteroids =7.5 mg/day). Thirteen stopped infliximab because of loss of efficacy (n = 4), remission (n = 6) or non-compliance, chest tightness or side effect (1 each). Ten patients relapsed (median interval 13 months), 3 while still receiving infliximab; 2 were successfully re-treated with infliximab. CONCLUSION: These observations highlight infliximab as a potentially useful and safe salvage treatment for patients with refractory SNV.
Asunto(s)
Antiinflamatorios/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Vasculitis/tratamiento farmacológico , Adulto , Anciano , Antiinflamatorios/administración & dosificación , Antiinflamatorios/efectos adversos , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Esquema de Medicación , Evaluación de Medicamentos , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Infliximab , Masculino , Persona de Mediana Edad , Prednisona/administración & dosificación , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
OBJECTIVES: Acquired von Willebrand's syndrome (AvWS) is an uncommon complication of monoclonal gammopathy of uncertain significance (MGUS) or myeloma. We investigated clinical and laboratory test abnormalities, pathophysiological hypotheses, and treatment options in this poorly known condition. PATIENTS: Five patients with MGUS and two with myeloma who met classic criteria for acquired von Willebrand's syndrome were included in this retrospective study. RESULTS: Acquired von Willebrand's syndrome was diagnosed before the gammopathy in five of the seven patients. The severity of the bleeding events was chiefly dependent on the degree of von Willebrand's factor deficiency and on the presence or absence of gastrointestinal tract angiodysplasia. Bleeding event severity was similar in patients with nonmalignant and malignant disease. An antibody that inhibited von Willebrand's factor was detected in all seven patients. Clotting returned to normal after treatment of the malignancy in one of the two patients with myeloma. In patients with MGUS, treatment is warranted only when bleeding occurs or before surgery. Von Willebrand's factor concentrates were of limited efficacy because of their short half-life. Intravenous immunoglobulins had a longer-lasting effect (about 3 weeks); this treatment was used on a regular basis in two patients with recurrent bleeding. CONCLUSIONS: A diagnosis of von Willebrand's syndrome in adulthood should prompt a search for a monoclonal gammopathy. In patients with gammopathies, simple clotting tests ensure the diagnosis of acquired von Willebrand's syndrome.
Asunto(s)
Mieloma Múltiple/patología , Paraproteinemias/patología , Enfermedades de von Willebrand/patología , Anciano , Anciano de 80 o más Años , Pruebas de Coagulación Sanguínea , Femenino , Hemorragia/etiología , Hemorragia/patología , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/complicaciones , Paraproteinemias/complicaciones , Estudios Retrospectivos , Enfermedades de von Willebrand/complicacionesRESUMEN
BACKGROUND: Low-complement urticarial vasculitis is an uncommon condition associating urticaria, glomerulonephritis, obstructive ventilatory disorders, and anti-Ciq antibodies. CASE REPORT: We report a case in a 34-year-old woman who developed urticaria with purpura, membranoproliferative glomerulonephritis (creatinine 238 mumol/l) and bronchial obstruction with bronchectasia. Total complement and the C3 fraction were low. Anti-C1q antibodies were found in the serum and anti-DNA antibodies were negative. Aggravation of the respiratory and renal failure progressed despite corticosteroid therapy, leading to death at 4 months. DISCUSSION: Bronchial obstruction in low-complement urticarial vasculitis results from emphysema and is often life-threatening. Our case exhibited an unusual feature due to the lack of radiodetectable emphysema, the presence of bronchectasia and the rapid degradation of the respiratory function.
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Proteínas del Sistema Complemento/deficiencia , Urticaria/inmunología , Vasculitis/inmunología , Adulto , Autoanticuerpos/sangre , Biopsia , Bronquiectasia/inmunología , Bronquiectasia/patología , Complemento C1q/inmunología , Resultado Fatal , Femenino , Mesangio Glomerular/inmunología , Mesangio Glomerular/patología , Glomerulonefritis/inmunología , Glomerulonefritis/patología , Humanos , Glomérulos Renales/inmunología , Glomérulos Renales/patología , Síndrome , Tomografía Computarizada por Rayos X , Urticaria/patología , Vasculitis/patologíaRESUMEN
The pharmacodynamic pattern of low molecular weight dermatan sulphate (CAS 24967-94-0, Desmin-LMWDS) was studied in patients presenting chronic renal insufficiency. Three groups of six patients were defined according to their creatinine clearance: group 1, more than 50 ml/min, group 2 between 10 and 50 ml/min and group 3 lower than 10 ml/min (haemodialized patients). Desmin-LMWDS concentrations were determined with the Heptest assay and the chromogenic specific heparin cofactor II dependent anti IIa assay. In patients of group 1 affected by moderate renal insufficiency, the pharmacodynamic profiles were roughly comparable to those obtained in normal subjects. In the two other groups, the profiles were markedly modified by the renal insufficiency. The maximal concentrations were doubled and the areas under the time-activity curve were 4-fold higher in haemodialyzed (group 3) and severe renal insufficient patients (group 2) than in patients of group 1. The clearance of the anti IIa activity were 13.98 +/- 6.25 l/h; 4.12 +/- 2.64 l/h and 2.94 +/- 1.53 l/h and the half-lives were 2.79 +/- 2.60 h, 6.15 +/- 4.02 h and 11.51 +/- 6.54 h in groups 1 to 3, respectively (p < 0.05). The Desmin-LMWDS clearance was directly correlated to the creatinine clearance (r = 0.8244, n = 18, p < 0.001). Thus, as for low molecular weight heparin, renal function plays a major role in the elimination of low molecular weight dermatan sulphate.
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Dermatán Sulfato/farmacocinética , Fallo Renal Crónico/metabolismo , Adulto , Anciano , Área Bajo la Curva , Dermatán Sulfato/administración & dosificación , Factor Xa/metabolismo , Femenino , Humanos , Inyecciones Subcutáneas , Masculino , Persona de Mediana Edad , Tiempo de Tromboplastina Parcial , Protrombina/metabolismo , Tiempo de TrombinaRESUMEN
Microscopic polyangiitis (MPA) is a systemic small-vessel vasculitis primarily associated with necrotizing glomerulonephritis and pulmonary capillaritis. In this retrospective study of 29 patients with MPA and alveolar hemorrhage (AH), we characterized the pulmonary manifestations at presentation and assessed the short- and long-term outcome. AH was diagnosed when bronchoalveolar lavage was macroscopically bloody, or contained hemosiderin-laden macrophages, in the absence of lung infection or pulmonary edema. MPA was diagnosed when AH was associated with focal segmental necrotizing glomerulonephritis at kidney biopsy or pathologically proved small-vessel vasculitis. There were 17 women and 12 men, with a mean age of 55.8 +/- 16.7 years. The onset was rapidly progressive, but in 8 (28%) patients, symptoms preceded the diagnosis for more than 1 year. The most constant systemic findings associated with AH were glomerulonephritis in 28 (97%) patients; fever (62%); myalgia and arthralgia (52%); weight loss (45%); ear, nose, and throat symptoms (31%); and skin involvement (17%). Lung opacities were bilateral in 26 (90%) patients, most frequently involving the lower part of the lungs. Bronchoalveolar lavage, performed in 27 patients, was hemorrhagic in 25 (93%), and contained numerous siderophages in others. Most patients were severely anemic (mean hemoglobin, 8.1 +/- 1.8 g/dL). ANCA, present in 27 (93%) patients, gave a perinuclear (14), cytoplasmic (11), or mixed (1) pattern. Mean serum creatinine level was 407 +/- 415 mumol/L. Renal biopsy confirmed the presence of necrotizing glomerulonephritis in 27 patients. Patients were treated with corticosteroids (100%), cyclophosphamide (79%), plasmapheresis (24%), dialysis (28%), and mechanical ventilation (10%). The overall mortality rate was 31% (9 patients). Deaths were related to vasculitis (5 patients) or side effects of treatment (4). Deaths were more frequent in aged or mechanically ventilated patients. The 5-year survival rate was 68%. The recovery of respiratory function among survivors was clinically considered complete in 20 (69%) patients. However, 7 patients (24%) had persistent alterations on pulmonary function tests. Of the 11 patients who had relapses, 2 died from AH.
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Hemorragia/etiología , Poliarteritis Nudosa/complicaciones , Alveolos Pulmonares/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Poliarteritis Nudosa/tratamiento farmacológico , Poliarteritis Nudosa/patología , Pronóstico , Respiración Artificial , Estudios Retrospectivos , Factores de RiesgoRESUMEN
The ubiquitous form of the sodium-hydrogen exchanger, NHE1, is devoted to the regulation of intracellular pH and cell volume. In addition, NHE1 activity is stimulated by growth factors and increased NHE rates are found in both circulating and immortalized cells during diabetes or diabetic nephropathy. In this context, we searched for polymorphisms of the 5'-flanking regulatory region of NHE1 gene in subjects with type-I diabetes. We identified a C/T transition 696 bases upstream the translation initiation start site which disrupts a repeated palindromic GC sequence. The TT genotype was significantly more frequent in type-1 diabetics and may have functional importance. Genetic linkage between NHE1 and diabetes has been previously described in NOD mice strains with consequences on NHE rates. Hence, the polymorphism described hereby may act as a predisposition factor to type-I diabetes or to diabetic complications, and may be useful to investigate the genetic involvement of NHE1 in human pathophysiology.
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Regiones no Traducidas 5' , Diabetes Mellitus Tipo 1/genética , Polimorfismo Genético , Intercambiadores de Sodio-Hidrógeno/genética , Animales , Humanos , RatonesRESUMEN
Fifty-seven cases of Ig light chain-associated Fanconi syndrome (FS) have been reported so far, mostly as isolated reports. The pioneering work by Maldonado and associates (35), who reviewed the first 17 cases in 1975, led to the unifying concept that patients with FS and Bence Jones proteinuria have a special form of plasma cell dyscrasia characterized by slow progression of the tumor and by prominent crystal formation in proximal tubule cells, in the absence of myeloma casts in the distal tubule. We carefully reappraised these characteristics in a series of 11 patients. Ten renal biopsy specimens were available for electron microscopy, adding to the 15 previously reported cases with ultrastructural studies. Moreover, 10 of the kappa light chains could be entirely or partially sequenced and tested for their resistance to cathepsin B, a lysosomal protease present in proximal tubule cells. Our series showed an unexpected clinicopathologic heterogeneity. Seven patients presented with the typical clinical and pathologic features of FS and low-mass myeloma or monoclonal gammopathy of undetermined significance (MGUS), in keeping with Maldonado et al's description. Crystals in bone marrow cells were detected in patients of this group, only. Three patients who presented with full-blown FS exhibited, however, the characteristic features of myeloma cast nephropathy in the setting of high-mass myeloma. One patient of this group also had numerous crystals in proximal tubule cells. The eleventh patient had complete FS with MGUS, but no crystals in proximal tubule cells even after electron microscopy. Contrasting with the clinicopathologic heterogeneity, genetic and biochemical analyses of the light chains showed a striking homogeneity. First, they all were of the kappa type. Second, 8 of 9 belonged to the V kappa I variability subgroup, which indicates that FS light chains are related by the sequence of their variable regions. Third, the 8 V kappa I light chain sequences most likely originated from only 2 germline genes, LCO2/012 and LCO8/018. Fourth, all 5 LCO2/012-derived sequences presented an unusual hydrophobic or nonpolar residue at position 30. These sequence peculiarities may account for unusual physicochemical properties of the light chains including the resistance of their variable domain V kappa to proteolysis by cathepsin B, observed in 7 of 9 patients in our series, while light chains isolated from patients with myeloma cast nephropathy are completely digested. Resistance of V kappa to proteolysis in FS patients can explain the accumulation of the light chain in the endocytotic compartment of the proximal tubule cells, leading to impairment of proximal tubule functions.
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Síndrome de Fanconi/inmunología , Paraproteinemias/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Síndrome de Fanconi/mortalidad , Síndrome de Fanconi/patología , Femenino , Humanos , Cadenas Ligeras de Inmunoglobulina/química , Cadenas Ligeras de Inmunoglobulina/orina , Cadenas kappa de Inmunoglobulina/química , Cadenas kappa de Inmunoglobulina/orina , Túbulos Renales Proximales/patología , Masculino , Persona de Mediana Edad , Mieloma Múltiple/etiología , Mieloma Múltiple/inmunología , Paraproteinemias/inmunología , Paraproteinemias/patologíaRESUMEN
Microscopic polyangiitis is a systemic necrotizing vasculitis affecting small vessels, without granulomata. Patients present with rapidly progressive glomerulonephritis, often associated with cutaneous, musculoskeletal, neurological or gastrointestinal involvement. Antineutrophilcytoplasmic antibodies are frequently found, most often with a perinuclear pattern and a antimyeloperoxidase specificity. Diagnosis is based on the evidence of a necrotizing glomerulonephritis, or histological vasculitis, in the absence of extravascular granulomata or sign of macroscopic polyarteritis nodosa. Corticosteroids and immunosuppressive drugs have improved the prognosis, but relapses are frequent.
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Vasculitis , Humanos , Microcirculación , Vasculitis/complicaciones , Vasculitis/diagnóstico , Vasculitis/tratamiento farmacológicoRESUMEN
We report on a case of methotrexate (MTX) intoxication occurring in a 19-year-old man treated for a leukemia. Exchange-transfusion (ET) was performed in attempt to remove the MTX from the body. This exchange-transfusion was unable to decrease the MTX plasma concentration. This inefficacy of ET in MTX intoxication is in contradiction with previously reported recommendations. However, this result is easily explained by MTX pharmacokinetics parameters.
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Lesión Renal Aguda/inducido químicamente , Antineoplásicos/envenenamiento , Recambio Total de Sangre , Metotrexato/envenenamiento , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Lesión Renal Aguda/terapia , Adulto , Antídotos/uso terapéutico , Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Diuréticos/uso terapéutico , Sobredosis de Droga/etiología , Sobredosis de Droga/terapia , Furosemida/uso terapéutico , Humanos , Leucovorina/uso terapéutico , Masculino , Metotrexato/administración & dosificación , Metotrexato/sangre , Pancitopenia/inducido químicamente , Insuficiencia del TratamientoRESUMEN
Acquired von Willebrand's disease associated with a monoclonal gammopathy and angiodysplasia of the gut is a rare disorder. It is sometimes complicated by chronic intestinal bleeding and severe anemia, that is poorly responsive to usual treatments. We report such a new case that has been revealed by anemia, and characterised by the absence of the high-molecular weight multimers. The correction of the hemostasis defect and of anemia were related to the reappearance of the high-molecular weight multimers, that was achieved only after high-dose intravenous immunoglobulin courses. The perfusions were performed every 3 weeks for 2 years without loss of efficiency, that could be explained by the dissociation of immunoglobulin-von Willebrand's factor complex.
Asunto(s)
Angiodisplasia/complicaciones , Inmunoglobulina G , Inmunoglobulinas Intravenosas/uso terapéutico , Paraproteinemias/complicaciones , Enfermedades de von Willebrand/complicaciones , Anciano , Angiodisplasia/tratamiento farmacológico , Humanos , Inmunoglobulinas Intravenosas/administración & dosificación , Intestino Delgado , Masculino , Paraproteinemias/tratamiento farmacológico , Factores de Tiempo , Enfermedades de von Willebrand/tratamiento farmacológicoRESUMEN
Plasma DNA that circulates mainly as mononucleosomes is a cell death marker. Its significance and prognostic value in cancer as compared to other tumour markers was investigated in 68 patients hospitalised for lung cancers. Prognostic values of the various studied parameters were evaluated using the Cox's model. The cellular origin of plasma DNA was further investigated in nude mice transplanted with human lung adenocarcinoma. Plasma DNA concentrations were increased in cancer patients as compared to normal subjects (P < 0.01). They were higher in patients with extended (Stage 4) disease than in patients with limited stage disease (P < 0.05). Plasma DNA concentrations, serum lactate dehydrogenase activities and neuron-specific enolase concentrations were correlated all together in small cell lung carcinoma (SCLC) and in non-SCLC. Similar relationships were found between survival and each of these three cell death/tumour markers (P < 0.02-0.005). Plasma DNA from mice bearing human tumour hybridised with both mouse and human plasma DNA, while plasma DNA from endotoxin-injected mice hybridised only with mouse plasma DNA. In conclusion, in patients suffering from lung cancer, plasma DNA as well as LDH and NSE represent cell death markers that are correlated with survival. At a time when apoptosis pathways appear to be potential targets for cancer therapy, plasma DNA is a cell death/tumour marker that should be taken into account in studying the cancerous process in human diseases.