RESUMEN
Systemic lupus erythematosus (SLE) is an inflammatory systemic disease that causes organ damage by the deposition of autoantibodies and complement activating immune complexes or by vascular occlusion due to procoagulant states associated with antiphospholipid antibodies. The vast majority of cases occur in women of childbearing age. SLE is diagnosed on the basis of its clinical manifestations and the demonstration of characteristic immunological phenomena, especially anti-nuclear antibodies. The prognosis in SLE has shown a distinct improvement over recent decades, the 5-year survival rate now approaching or exceeding 90%. The 15-year survival rate of 63 to 79%, on the other hand, underscores the need for further advances in diagnosis and treatment of the disease. Management of the disease includes regular monitoring of disease activity, avoidance of predisposing factors and close supervision of therapy. Drug therapy is guided by the activity and severity of the leading organ manifestations and ranges from nonsteroidal antirheumatic drugs to intensive treatment with cytotoxic agents. Corticosteroids remain irreplaceable for the control of acute flares. Antimalarials and azathioprine are important long term drugs for treating mild or moderate disease activity. Intravenous pulse cyclophosphamide is safer than other regimens and at least as effective as oral cyclophosphamide for severe lupus nephritis. It is also effective in the treatment of central nervous disease and of other organ-threatening manifestations. Recently, an intensified protocol which included cyclophosphamide induced long term treatment-free remission in 60% of patients. The toxicity of cyclophosphamide is considerable, but can be ameliorated by various measures. The value of several new immunosuppressants and other compounds remains to be determined.
Asunto(s)
Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/fisiopatología , Corticoesteroides/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Femenino , Humanos , PronósticoRESUMEN
Since the effectiveness of high dose intravenous immunoglobulin (IVIg) was first demonstrated in autoimmune thrombocytopenia, IVIg has been investigated in the treatment of various autoimmune rheumatic disorders. Controlled randomised studies have established the efficacy of IVIg in Kawasaki's syndrome, for which combined IVIg and aspirin (acetylsalicylic acid) now constitutes the standard treatment. Another controlled study has demonstrated the benefit of IVIg in dermatomyositis. IVIg treatment in juvenile rheumatoid arthritis has produced contradictory results. Uncontrolled studies and case reports on the application of IVIg in systemic lupus erythematosus, ANCA-associated vasculitides and adult rheumatoid arthritis generally describe short term positive effects. Various mechanisms are thought to underlie the effect of IVIg on autoimmune rheumatic diseases, such as: blockade of Fc receptors;immunomodulation via anti-idiotypic interactions;inhibition of complement-mediated tissue damage;modulation of cytokine expression by leucocytes and endothelial cells; andinhibition of superantigen-mediated T cell activation. IVIg is considered to be a low-risk form of treatment. Reported adverse effects include headache, aseptic meningitis and transient impairment of renal function. Haemolysis and anaphylactic reactions are rare. The effect profile of IVIg makes it a relevant, although still experimental, form of treatment in autoimmune rheumatic disorders, but its high cost renders it unsuitable as a first-line treatment. Because IVIg does not weaken patients' resistance to infection, it might serve as a therapeutic option in bridging clinical situations where immunosuppressive or cytotoxic approaches are contraindicated in patients with autoimmune disorders, such as intercurrent infection or in the period immediately before and after surgery.
RESUMEN
A group of clinics cooperating as the Lupus Plasmapheresis Study Group (LPSG) is starting an international multicenter study of the treatment of severe systemic lupus erythematosus. The primary goal of this randomized and prospective trial is to establish whether treatment with plasmapheresis and subsequent pulse cyclophosphamide improves the outcome compared to treatment with pulse cyclophosphamide alone. The underlying rationale assumes that plasmapheresis: a) eliminates pathogenic autoantibodies and immune complexes and b) induces a compensatory activation of pathogenic lymphocyte clones through a feed-back between circulating antibodies and their respective antibody-producing clones. Synchronization of plasmapheresis with subsequent pulse cyclophosphamide should enhance the deletion of pathogenic clones during the period of greatest vulnerability. This overview reviews the first results of treatment approaches based on this concept and summarizes the design of the LPSG trial.
Asunto(s)
Ciclofosfamida/administración & dosificación , Lupus Eritematoso Sistémico/terapia , Plasmaféresis , Terapia Combinada , Humanos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Estudios ProspectivosRESUMEN
For 12 years, a 26-year-old man had acne conglobata and a non-suppurative diffuse sclerosing osteomyelitis of the mandible as part of a chronic recurrent multifocal osteomyelitis of the sternum, the pelvic bones, and the femoral head, and aseptic arthritis of the knee, the fibulotalar, and the sternoclavicular joints. This fulfills the formal criteria of the SAPHO syndrome. Repeated surgical and antibiotic treatment combined with hyperbaric oxygen caused partial improvement. Complete relief and partial disappearance of the scintigraphic lesions was achieved with long-term corticosteroids, non-steroidal anti-inflammatory drugs, minocycline, and isotretinoin.
Asunto(s)
Acné Vulgar/etiología , Síndrome de Hiperostosis Adquirido/complicaciones , Enfermedades Mandibulares/etiología , Osteomielitis/etiología , Acné Vulgar/tratamiento farmacológico , Síndrome de Hiperostosis Adquirido/diagnóstico por imagen , Síndrome de Hiperostosis Adquirido/patología , Adulto , Combinación Amoxicilina-Clavulanato de Potasio/uso terapéutico , Antiinflamatorios/uso terapéutico , Fármacos Dermatológicos/uso terapéutico , Quimioterapia Combinada/uso terapéutico , Humanos , Isotretinoína/uso terapéutico , Masculino , Enfermedades Mandibulares/diagnóstico por imagen , Enfermedades Mandibulares/tratamiento farmacológico , Enfermedades Mandibulares/patología , Osteomielitis/diagnóstico por imagen , Osteomielitis/tratamiento farmacológico , Osteomielitis/patología , Prednisolona/uso terapéutico , CintigrafíaAsunto(s)
Hemorragia Gastrointestinal/inducido químicamente , Heparina/efectos adversos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Enfermedad Aguda , Adulto , Femenino , Hemorragia Gastrointestinal/complicaciones , Heparina/administración & dosificación , Heparina/uso terapéutico , Humanos , Inyecciones Subcutáneas , Choque Hemorrágico/etiologíaAsunto(s)
Formación de Anticuerpos , Ciclofosfamida/uso terapéutico , Terapia de Inmunosupresión/métodos , Lupus Eritematoso Sistémico/inmunología , Páncreas/inmunología , Plasmaféresis , Animales , Formación de Anticuerpos/efectos de los fármacos , Complejo Antígeno-Anticuerpo , Terapia Combinada , Humanos , Lupus Eritematoso Sistémico/terapia , Valores de Referencia , PorcinosRESUMEN
Two patients with severe systemic lupus erythematosus, who had not responded to conventional therapy, were treated with plasmapheresis and subsequent pulse cyclophosphamide. This approach uses the plasmapheresis-induced proliferation of pathogenic clones for partial clonal deletion by giving large doses of cytotoxic drugs during the assumed period of increased B-cell vulnerability. Both patients had a rapid and distinct improvement in clinical symptoms and laboratory parameters, including the control of a life-threatening case of lupus pneumonitis. Their conditions were stabilized by giving low-dose cyclophosphamide for the next 6 months. At 14-month follow-up, there were no clinical signs of relapse.
Asunto(s)
Ciclofosfamida/administración & dosificación , Lupus Eritematoso Sistémico/terapia , Plasmaféresis , Administración Oral , Adulto , Terapia Combinada , Esquema de Medicación , Quimioterapia Combinada , Femenino , Humanos , Infusiones Intravenosas , Prednisolona/administración & dosificaciónRESUMEN
Assessing disease activity in SLE is often difficult due to the multiple organ systems involved. Three recent disease activity indices (SLAM, BILAG, and SLEDAI) are being increasingly used. Retrospective investigations comparing these indices have not been performed. We compared SLAM, BILAG, and SLEDAI in a retrospective study of 52 patients with SLE. SLAM and BILAG were found to correlate well with one another and with clinicians' evaluations of disease activity (as measured by intensity of immunosuppressive treatment). They correlated less well or insignificantly with laboratory parameters (ESR, anti-ds-DNA-antibodies). If practicability is also considered, SLAM, in particular, appears to be suitable for retrospective evaluation of disease activity in SLE.
Asunto(s)
Lupus Eritematoso Sistémico/diagnóstico , Índice de Severidad de la Enfermedad , Adolescente , Adulto , Anciano , Anticuerpos Antinucleares/análisis , ADN/inmunología , Femenino , Humanos , Lupus Eritematoso Sistémico/clasificación , Lupus Eritematoso Sistémico/inmunología , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
OBJECTIVE: To investigate the effect of an intensified treatment protocol synchronizing plasmapheresis with subsequent pulse cyclophosphamide for severe systemic lupus erythematosus (SLE). METHODS: A protocol of plasmapheresis (3 x 60 ml/kg) and subsequent high-dose pulse cyclophosphamide (36 mg/kg) followed by 6 months of peroral immunosuppression was used to treat 14 patients with severe SLE. RESULTS: Rapid improvement was achieved in all patients. Immunosuppressants, including corticosteroids, were withdrawn at month 6 in 12 patients. Eight patients continued without treatment for a mean observation period of 5.6 years (46-91 months). CONCLUSION: The results demonstrate that treatment-free clinical remission can be achieved in some patients with severe SLE.
Asunto(s)
Ciclofosfamida/uso terapéutico , Lupus Eritematoso Sistémico/terapia , Plasmaféresis , Adolescente , Adulto , Amenorrea/fisiopatología , Complemento C4/análisis , Complemento C4/deficiencia , Creatinina/sangre , Ciclofosfamida/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Inmunoglobulinas/metabolismo , Cinética , Recuento de Leucocitos , Leucopenia/etiología , Lupus Eritematoso Sistémico/complicaciones , Persona de Mediana Edad , Embarazo , Complicaciones del Embarazo/fisiopatología , Flujo Pulsátil , Factores de TiempoRESUMEN
OBJECTIVE: To investigate the effect of high dose intravenous immunoglobulins (IVIG) in systemic lupus erythematosus (SLE). METHODS: Twelve patients with mildly to moderately active disease were given 30 g of sulfonated IVIG preparation on each of Days 1-4 and 21-24. RESULTS: Within 6 weeks the mean disease activity score, the Systemic Lupus Activity Measure (SLAM), declined from 7.33 (range 3-15) to 5.25 (range 0-10) (p < 0.01). In 9/12 patients the SLAM dropped by at least 2 points. In 3/12 patients the improvement lasted 5 to 12 months. Within 1 week after initiation of therapy most patients showed a decline in ds-DNA antibodies, whereas titers of antinuclear antibodies and complement proteins were not affected. The treatment was well tolerated, with the exception of transient hypotension in one patient. CONCLUSION: In this uncontrolled study, IVIG had temporary beneficial effects in mildly to moderately active SLE.
Asunto(s)
Inmunoglobulinas Intravenosas/farmacología , Lupus Eritematoso Sistémico/tratamiento farmacológico , Adolescente , Adulto , Anticuerpos Antinucleares/biosíntesis , Protocolos Clínicos , Complemento C3/biosíntesis , Complemento C4/biosíntesis , Daño del ADN , Femenino , Humanos , Inmunoglobulinas Intravenosas/economía , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/patología , Persona de Mediana Edad , Proyectos Piloto , Recuento de Plaquetas/efectos de los fármacos , Índice de Severidad de la EnfermedadRESUMEN
The investigation of antibody kinetics following antigen-specific immunoadsorption in alkaline phosphatase immunized rats revealed significantly lower antibody levels than in untreated controls over a follow-up period of 6 weeks. A rebounding antibody synthesis as a result of specific depletion was not observed. Non-adsorption of specific antiidiotypic antibodies may explain these findings.
Asunto(s)
Fosfatasa Alcalina/inmunología , Anticuerpos/aislamiento & purificación , Antígenos/inmunología , Inmunización , Técnicas de Inmunoadsorción , Modelos Biológicos , Fosfatasa Alcalina/administración & dosificación , Animales , Anticuerpos/metabolismo , Especificidad de Anticuerpos , Bromuro de Cianógeno/química , Femenino , Ratas , Ratas Sprague-Dawley , Sefarosa/químicaRESUMEN
11 patients with severe SLE were treated with plasmapheresis and subsequent pulse cyclophosphamide. In all patients rapid improvement was observed. After another 6 months of immunosuppression any treatment was withdrawn. The remissions remained stable in 6/8 patients during the follow-up period of 7-33 (mean: 21) months.
Asunto(s)
Ciclofosfamida/uso terapéutico , Terapia de Inmunosupresión , Lupus Eritematoso Sistémico/terapia , Plasmaféresis , Femenino , Humanos , Inducción de RemisiónRESUMEN
We report on a 54-year-old female patient with arthritis and a severe cold-induced leukocytoclastic vasculitis of the skin caused by a rare form of cryofibrinogenemia ("type II" cryofibrinogen). Affinity chromatography of cryoprecipitates from the patient's plasma revealed reversible cryoprecipitability of complexes composed of fibrinogen and a monoclonal antifibrinogen antibody (IgG3 kappa). Conventional serum and plasma electrophoresis did not detect the paraprotein. Control of symptoms was achieved by long-term plasmapheresis.
Asunto(s)
Crioglobulinas , Fibrinógeno , Fibrinógenos Anormales , Inmunoglobulina G/inmunología , Paraproteinemias/complicaciones , Vasculitis Leucocitoclástica Cutánea/etiología , Femenino , Humanos , Persona de Mediana Edad , Paraproteinemias/terapia , Vasculitis Leucocitoclástica Cutánea/terapiaRESUMEN
A 47-year old woman is presented who had a left adrenal pheochromocytoma with manifestations also indicative of ectopic ACTH syndrome. The excised adrenal gland showed both an adrenal medullary tumor and adrenal cortical hyperplasia. Immunostaining also showed the presence in the tumor of ACTH and beta endorphins. The immediate post-adrenalectomy decline of catecholamines, ACTH, cortisol and beta endorphins indicate that the adrenal itself was the source of these hormones. This patient, the thirteenth now reported in the literature, represents one form of ectopic ACTH syndrome in which the lesion is benign, and in which a successful outcome can be anticipated.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales/metabolismo , Hormona Adrenocorticotrópica/metabolismo , Endorfinas/metabolismo , Feocromocitoma/metabolismo , Corteza Suprarrenal/patología , Pruebas de Función de la Corteza Suprarrenal , Neoplasias de las Glándulas Suprarrenales/patología , Neoplasias de las Glándulas Suprarrenales/ultraestructura , Médula Suprarrenal/patología , Catecolaminas/orina , Dexametasona , Femenino , Histocitoquímica , Humanos , Técnicas para Inmunoenzimas , Persona de Mediana Edad , Feocromocitoma/patología , Feocromocitoma/ultraestructura , betaendorfinaRESUMEN
OBJECTIVE: To assess the efficacy of pulse/synchronization cyclophosphamide/apheresis in patients with proliferative lupus nephritis. METHODS: Eighteen patients with Class III or IV renal biopsies and chronicity indices <6 were prospectively randomized to receive 6 courses of parenteral cyclophosphamide over 8 months along with prednisone. Nine of these patients also received 3 daily plasmaphereses prior to each of the 6 courses of cyclophosphamide. Assessments compiled at 6 and 24 months included serum creatinine, albumin, anti DNA, 24-hour urine protein, and C3 complement along with SLAM scores. RESULTS: Two out of nine patients in each group evolved end stage renal disease and 3/9 patients in each group went into a renal remission at 24 months. Serum albumin, C3 complement, and SLAM scores improved in both groups, and anti-DNA improved in the pulse/synchronization patients (P < 0.025). No intergroup comparisons were significant. CONCLUSION: The addition of pulse/synchronization apheresis to cyclophosphamide therapy does not improve the course of patients with proliferative lupus nephritis.