RESUMEN
Gitelman syndrome (GS) is a rare, salt-losing tubulopathy characterized by hypokalemic metabolic alkalosis with hypomagnesemia and hypocalciuria. The disease is recessively inherited, caused by inactivating mutations in the SLC12A3 gene that encodes the thiazide-sensitive sodium-chloride cotransporter (NCC). GS is usually detected during adolescence or adulthood, either fortuitously or in association with mild or nonspecific symptoms or both. The disease is characterized by high phenotypic variability and a significant reduction in the quality of life, and it may be associated with severe manifestations. GS is usually managed by a liberal salt intake together with oral magnesium and potassium supplements. A general problem in rare diseases is the lack of high quality evidence to inform diagnosis, prognosis, and management. We report here on the current state of knowledge related to the diagnostic evaluation, follow-up, management, and treatment of GS; identify knowledge gaps; and propose a research agenda to substantiate a number of issues related to GS. This expert consensus statement aims to establish an initial framework to enable clinical auditing and thus improve quality control of care.
Asunto(s)
Síndrome de Bartter/diagnóstico , Condrocalcinosis/etiología , Suplementos Dietéticos , Síndrome de Gitelman/diagnóstico , Síndrome de Gitelman/tratamiento farmacológico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Síndrome de Bartter/sangre , Síndrome de Bartter/genética , Síndrome de Bartter/orina , Calcio/orina , Canales de Cloruro/genética , Condrocalcinosis/prevención & control , Conferencias de Consenso como Asunto , Diagnóstico Diferencial , Pruebas Genéticas , Síndrome de Gitelman/complicaciones , Síndrome de Gitelman/genética , Humanos , Hipopotasemia/sangre , Hipopotasemia/genética , Magnesio/administración & dosificación , Magnesio/sangre , Magnesio/uso terapéutico , Mutación , Fenotipo , Potasio/administración & dosificación , Potasio/sangre , Potasio/uso terapéutico , Guías de Práctica Clínica como Asunto , Calidad de Vida , Enfermedades Raras/genética , Cloruro de Sodio Dietético/uso terapéutico , Miembro 3 de la Familia de Transportadores de Soluto 12/genética , UltrasonografíaRESUMEN
Microcrystals of calcium pyrophosphate dihydrate (CPPD) and monosodium urate (MSU) deposited in synovium and articular cartilage initiate joint inflammation and cartilage degradation in large part by binding and directly activating resident cells. TLRs trigger innate host defense responses to infectious pathogens, and the expression of certain TLRs by synovial fibroblasts has revealed the potential for innate immune responses to be triggered by mesenchymally derived resident cells in the joint. In this study we tested the hypothesis that chondrocytes also express TLRs and that one or more TLRs centrally mediate chondrocyte responsiveness to CPPD and MSU crystals in vitro. We detected TLR2 expression in normal articular chondrocytes and up-regulation of TLR2 in osteoarthritic cartilage chondrocytes in situ. We demonstrated that transient transfection of TLR2 signaling-negative regulator Toll-interacting protein or treatment with TLR2-blocking Ab suppressed CPPD and MSU crystal-induced chondrocyte release of NO, an inflammatory mediator that promotes cartilage degeneration. Conversely, gain-of-function of TLR2 in normal chondrocytes via transfection was associated with increased CPPD and MSU crystal-induced NO release. Canonical TLR signaling by parallel pathways involving MyD88, IL-1R-associated kinase 1, TNF receptor-associated factor 6, and IkappaB kinase and Rac1, PI3K, and Akt critically mediated NO release in chondrocytes stimulated by both CPPD and MSU crystals. We conclude that CPPD and MSU crystals critically use TLR2-mediated signaling in chondrocytes to trigger NO generation. Our results indicate the potential for innate immunity at the level of the articular chondrocyte to directly contribute to inflammatory and degenerative tissue reactions associated with both gout and pseudogout.
Asunto(s)
Pirofosfato de Calcio/toxicidad , Condrocitos/efectos de los fármacos , Condrocitos/metabolismo , Glicoproteínas de Membrana/metabolismo , Óxido Nítrico/biosíntesis , Receptores de Superficie Celular/metabolismo , Ácido Úrico/toxicidad , Proteínas Adaptadoras Transductoras de Señales , Animales , Antígenos de Diferenciación/metabolismo , Secuencia de Bases , Pirofosfato de Calcio/metabolismo , Bovinos , Células Cultivadas , Condrocalcinosis/etiología , Condrocalcinosis/inmunología , Condrocalcinosis/metabolismo , Condrocitos/inmunología , Cristalización , ADN Complementario/genética , Expresión Génica , Gota/etiología , Gota/inmunología , Gota/metabolismo , Humanos , Quinasa I-kappa B , Inmunidad Innata , Quinasas Asociadas a Receptores de Interleucina-1 , Glicoproteínas de Membrana/antagonistas & inhibidores , Glicoproteínas de Membrana/genética , Modelos Biológicos , Factor 88 de Diferenciación Mieloide , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-akt , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores de Superficie Celular/antagonistas & inhibidores , Receptores de Superficie Celular/genética , Receptores Inmunológicos/metabolismo , Transducción de Señal , Factor 6 Asociado a Receptor de TNF/metabolismo , Receptor Toll-Like 2 , Receptores Toll-Like , Ácido Úrico/metabolismo , Proteína de Unión al GTP rac1/metabolismoRESUMEN
A 82-year-old woman was admitted because of dehydration and chronic renal failure. Although her renal function was improved by hydration, granulocytopenia (granulocyte number 645/mm3) occurred. Treatment with a relatively high dose of H2 blocker for one month before admission may have caused the granulocytopenia. To prevent possible infection in the patient, we administered 75 g of granulocyte-colony stimulating factor (G-CSF) for 5 consecutive days but 4 days after commencement of administration of G-CSF, pain in both knee joints suddenly appeared. Synovial fluid aspiration revealed granulocytosis (10,400/mm3) and deposition of calcium pyrophosphate dihydrate in the knee joints. The level of G-CSF in the synovial fluid was increased in the joints (700 pg/ml), compared with the serum concentration (62 pg/ml). Furthermore, the concentrations of interleukin-6 and interleukin-8 were markedly increased in the synovial fluid. The results indicated that her pseudogout exacerbation by G-CSF was at least in part explained by the increased production of cytokines in the knee joints. Because the prevalence of pseudogout and gout is overwhelming in the elderly, the possibility of GCSF induced exacerbation of joint pain should be carefully considered in elderly patients.
Asunto(s)
Agranulocitosis/inducido químicamente , Condrocalcinosis/etiología , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Anciano , Anciano de 80 o más Años , Agranulocitosis/terapia , Femenino , Antagonistas de los Receptores H2 de la Histamina/efectos adversos , HumanosRESUMEN
We report two cases of pseudogout after parathyroidectomy by primary hyperparathyroidism. The pseudogout in each instance developed within 48 hours after parathyroid adenoma resection. Calcium supplement therapy, nonsteroidal anti-inflammatory drugs and colchicine (1 mg/day) suppressed the acute attack. The chondrocalcinosis is often asymptomatic or undiagnosed, for that, preoperative radiological studies of the knees, wrists and pelvis are recommended to screen for chondrocalcinosis. We advocate also, therapy with colchicine (1 mg/day, oral) in the prophylaxis of postoperative pseudogout.
Asunto(s)
Adenoma/cirugía , Condrocalcinosis/etiología , Hiperparatiroidismo/etiología , Neoplasias de las Paratiroides/cirugía , Paratiroidectomía/efectos adversos , Complicaciones Posoperatorias , Adenoma/complicaciones , Adenoma/patología , Anciano , Condrocalcinosis/diagnóstico por imagen , Condrocalcinosis/prevención & control , Colchicina/uso terapéutico , Femenino , Supresores de la Gota/uso terapéutico , Humanos , Articulación de la Rodilla/diagnóstico por imagen , Persona de Mediana Edad , Glándulas Paratiroides/patología , Neoplasias de las Paratiroides/complicaciones , Neoplasias de las Paratiroides/patología , Radiografía , Factores de TiempoRESUMEN
A female patient aged 45 years is described with a rare form of chondrocalcinosis caused by hypomagnesaemia due to excessive renal loss of magnesium. The patient also had impaired renal conservation of potassium leading to a hypokalemia. She most probably had an idiopathic renal tubular dysfunction. Magnesium supplementation prevented further symptoms. Therefore in young patients with chondrocalcinosis it can be of therapeutic importance to search for an underlying treatable metabolic disorder.
Asunto(s)
Condrocalcinosis/etiología , Deficiencia de Magnesio/complicaciones , Condrocalcinosis/tratamiento farmacológico , Femenino , Humanos , Hipopotasemia/tratamiento farmacológico , Hipopotasemia/etiología , Magnesio/uso terapéutico , Deficiencia de Magnesio/tratamiento farmacológico , Persona de Mediana Edad , Potasio/uso terapéutico , Defectos Congénitos del Transporte Tubular Renal/complicacionesRESUMEN
Authors describe the case of a 43 years old male patient with complaints and restriction of motions since years, localized on the talocrural joint. In the background of the disease, responding inadequately to the therapy, calcium pyrophosphate depositions were found in the joint tissues. As the pathomechanism of the disease is even presently not cleared authors summarize our present knowledge referring to this problem.
Asunto(s)
Articulación del Tobillo/fisiopatología , Artritis/metabolismo , Pirofosfato de Calcio/metabolismo , Difosfatos/metabolismo , Adulto , Articulación del Tobillo/patología , Artritis/patología , Artritis/fisiopatología , Pirofosfato de Calcio/análisis , Condrocalcinosis/diagnóstico , Condrocalcinosis/etiología , Humanos , Masculino , Líquido Sinovial/análisis , Líquido Sinovial/metabolismoAsunto(s)
Terapia por Acupuntura/historia , Artropatía Neurógena/historia , Condrocalcinosis/historia , Puntos de Acupuntura , Artropatía Neurógena/etiología , Condrocalcinosis/etiología , Cristalografía/historia , Francia , Historia del Siglo XVII , Historia del Siglo XIX , Humanos , Japón , Países BajosRESUMEN
The level of parathyroid hormone was measured by heterologue C terminal radio-immunological assay in 69 patients with clinical or radiological manifestations of the type seen in primary articular chondrocalcinosis. They were divided into three groups: P1 with undetermined clinical arthropathies; P2 with sub-chondral and arthosic arthropathies; P3 with radiologically definite chondrocalcinosis. They were compared with 57 control subjects broken up into four groups: T1 with chronic rheumatic arthritis, T2 with low back pain, T3 with primary hyperparathyroidism due to adenoma, and T4 with secondary hyperparathyroidism with renal insufficiency. A form of normocalcemic hyperparathormonaemia was demonstrated in more than one out of two patients in group P1 (15/29). It was seen in three-quarters of the cases in group P2 (12/16). And it was seen in more than a quarter of the cases in group P3 (7/24). This hyperparathormonaemia was statistically significant only in groups P1 and P2 compared to the normals in groups T1 and T2. The results we obtained in this study seem to be in complete concordance with those we obtained earlier in idiopathic hemochromatosis. This hyperparathormonaemia seems to regress with age and is often only discovered when the characteristic articular lesions have appeared. The discovery of normocalcemic hyperparathormonaemia several years before the appearance of the radiological signs of the disease would appear to be an important argument in favour of the diagnosis of early articular chondrocalcinosis. The existence of raised parathyroid hormone in primary articular chondrocalcinosis as well as in idiopathic hemachromatosis is special etiopathogenic interest even if there remain numerous questions concerning its origin and mode of action.
Asunto(s)
Calcio/sangre , Condrocalcinosis/etiología , Hiperparatiroidismo/complicaciones , Hormona Paratiroidea/sangre , Adulto , Anciano , Condrocalcinosis/sangre , Creatinina/sangre , Femenino , Humanos , Artropatías/sangre , Artropatías/etiología , Masculino , Persona de Mediana Edad , Fósforo/sangreRESUMEN
The association of hypophosphatasia and pyrophosphate arthropathy in an adult patient has been described on 1 previous occasion. We report a further 2 patients with this disease combination. One patient suffers from the type of hypophosphatasia that presents in adult life, with fractures that are either spontaneous or the result of minimal trauma. The other patient suffered from the severe type of hypophosphatasia that presents in infancy but survived longer than is usual; the necropsy findings on this patient are reported.
Asunto(s)
Artritis/etiología , Pirofosfato de Calcio/metabolismo , Condrocalcinosis/etiología , Difosfatos/metabolismo , Hipofosfatasia/complicaciones , Artritis/metabolismo , Artritis/patología , Huesos/patología , Cartílago Articular/patología , Preescolar , Condrocalcinosis/metabolismo , Condrocalcinosis/patología , Femenino , Fracturas Espontáneas/etiología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Four patients with chondrocalcinosis of the knees volunteered for joint lavage. Preliminary experiments indicated that disodium EDTA and magnesium ions were potent solubilizers of CPPD crystals. The procedure was a therapeutic failure in that insignificant amounts of CPPD were removed and all 4 subjects developed postlavage attacks of pseudogout. It is hypothesized that the acute attack of pseudogout is a result of crystal shedding and may be triggered by any factor that enhances CPPD solubility.