RESUMEN
An 80-year-old man with long-standing rheumatoid arthritis presented with severe neck pain. No preceding trauma had occurred and he had no neurological complaints. A CT scan revealed vertical atlanto-axial subluxation without compression of the medulla oblongata. After conservative treatment the pain diminished. There were no neurological complications at follow-up.
Asunto(s)
Artritis Reumatoide/complicaciones , Articulación Atlantoaxoidea , Luxaciones Articulares , Dolor de Cuello , Anciano de 80 o más Años , Articulación Atlantoaxoidea/diagnóstico por imagen , Articulación Atlantoaxoidea/patología , Articulación Atlantoaxoidea/fisiopatología , Tratamiento Conservador , Humanos , Luxaciones Articulares/diagnóstico , Luxaciones Articulares/etiología , Luxaciones Articulares/fisiopatología , Luxaciones Articulares/terapia , Masculino , Dolor de Cuello/diagnóstico , Dolor de Cuello/etiología , Tomografía Computarizada por Rayos X/efectos adversos , Resultado del TratamientoRESUMEN
A 81-year-old woman presented with progressive pain, stiffness and swelling of the right thumb. She also complained of dysphagia and Raynaud's phenomenon. Physical examination revealed sclerodactyly and telangiectasia. A plain X-ray showed marked calcifications of the flexor tendon of the right thumb and esophagography demonstrated decreased motility of the lower esophagus. Additionally, anticentromere antibodies were positive. As a result, the patient was diagnosed with calcinosis as a presenting symptom of limited systemic scleroderma.
Asunto(s)
Enfermedad de Raynaud/diagnóstico , Esclerodermia Limitada/diagnóstico , Pulgar/patología , Anciano de 80 o más Años , Autoanticuerpos/análisis , Centrómero/inmunología , Femenino , Humanos , Enfermedad de Raynaud/inmunología , Esclerodermia Limitada/inmunologíaRESUMEN
OBJECTIVES: A previous 24-week randomised trial demonstrated that sulfasalazine (SSZ) treatment was superior to placebo (PLAC) in suppressing disease activity in patients with oligo- and polyarticular onset juvenile idiopathic arthritis (JIA). The current study determines the long-term outcome of the trial participants and evaluates whether the benefits of SSZ allocation are sustained over time. METHODS: Between 2001 and 2003, 32 SSZ and 29 PLAC patients (90% of all patients) were prospectively examined clinically and by chart review, median 9 years (range 7 to 10) after trial inclusion. In the follow-up assessment, variables of the American College of Rheumatology Pediatric 30 (ACR Pedi 30) criteria were collected. The assessor was blinded to trial treatment allocation. RESULTS: After the trial, patients had been routinely followed in rheumatology referral centres, and treated at the discretion of the attending physician. Almost all patients continued or started disease-modifying antirheumatic drugs (DMARDs) (SSZ 91%, PLAC 93%; SSZ treatment in about 80%). DMARD treatment appeared less intensive in the SSZ group as evidenced by a significantly shorter duration of SSZ use (median 2.5 vs 5.2 years; p = 0.02) and a trend towards less use of methotrexate and other DMARDs. More than one-third of the patients reported long periods of non-compliance with DMARD treatment in both groups. At follow-up, 74% of the patients had active joints, and 30% showed active polyarthritis. Almost all outcome scores were better for SSZ compared with PLAC patients. Differences (often exceeding 50%) were significant for the number of active joints, patients' overall well-being, number of patients with episodes of clinical remission off medication (CROM) and duration of these episodes, patients in CROM and ACR Pedi 30 response at follow-up. Additional exploratory analyses performed to detect potential confounders related to patient characteristics or follow-up treatment showed that DMARD treatment compliance was positively correlated with an ACR Pedi 30 response (odds ratio 3.8, 95% confidence interval (CI) 1.1 to 13.4; p = 0.03). Adjusted for compliance, an SSZ patient was 4.2 times as likely as a PLAC patient to be an ACR Pedi 30 responder at follow-up (95% CI 1.3 to 14.3; p = 0.02). CONCLUSIONS: This follow-up study shows that effective suppression of disease activity by SSZ treatment early in active disease in JIA patients has beneficial effects that persist for many years. Given these results, compliance with DMARD treatment deserves serious attention.
Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Juvenil/tratamiento farmacológico , Sulfasalazina/uso terapéutico , Adolescente , Antirreumáticos/administración & dosificación , Niño , Preescolar , Esquema de Medicación , Quimioterapia Combinada , Métodos Epidemiológicos , Femenino , Humanos , Masculino , Metotrexato/uso terapéutico , Cooperación del Paciente , Índice de Severidad de la Enfermedad , Sulfasalazina/administración & dosificación , Resultado del TratamientoRESUMEN
OBJECTIVE: To evaluate the sensitivity to change of a newly developed radiologic assessment tool, the Dijkstra score, and to develop a numeric composite score and progressor classification scheme to apply in juvenile idiopathic arthritis (JIA) trials. METHODS: A placebo-controlled trial of sulfasalazine (SSZ) in patients with oligoarticular- and polyarticular-onset JIA yielded the data for this study. Data were obtained from 418 sets of radiographs of the clinically involved and contralateral joints (at study entry and at 6 months' followup) from 66 JIA patients. The Dijkstra score assesses the presence or absence of swelling, osteopenia, joint space narrowing, growth abnormalities, subchondral bone cysts, erosions, and malalignment. These signs were combined in the Dijkstra composite score, to assess inflammation (DI), growth (DG), and damage (DD). Progression was defined as an increase in either the DG or the DD score. Scores were evaluated among all radiographs, a standard set of films (hand, foot, and knee), and per patient. All scores were used to explore differences between the 2 treatment groups. RESULTS: Over time, 58% of joints remained normal, 23% remained abnormal but stable, 14% showed an increase in signs, and 5% showed a decrease in signs. Of the 66 JIA patients, 12% had normal radiographic findings throughout followup, 27% showed abnormalities at some sites without change, and 61% showed change in at least 1 site. Changes in the DI, DG, and DD scores varied considerably per type of joint and occurred most frequently in joints of the standard set. DI and DG scores changed most often in the knees, while DD scores changed primarily in the hands and feet. The disease course in 8% of joints was classified as progressive. Films of SSZ-treated patients, versus the placebo group, showed less deterioration by the DD scores (P = 0.04), and the disease course was more often classified as nonprogressive in the SSZ group (P = 0.037). When progressors were defined as those who had at least one radiograph showing progression, significantly more placebo-treated patients were considered progressors (P = 0.046). CONCLUSION: In this trial data set, the Dijkstra composite score and the resulting progressor classification system are comprehensive and feasible tools that are sensitive to change and discriminate between clinical situations. They should now be tested by other investigators and in other data sets.
Asunto(s)
Artritis Juvenil/patología , Artrografía/métodos , Reumatología/métodos , Índice de Severidad de la Enfermedad , Antirreumáticos/uso terapéutico , Artritis Juvenil/clasificación , Artrografía/normas , Niño , Progresión de la Enfermedad , Femenino , Humanos , Articulaciones/patología , Masculino , Reumatología/normas , Sulfasalazina/uso terapéutico , Resultado del TratamientoRESUMEN
UNLABELLED: Five patients with multicentric carpal-tarsal osteolysis are presented: a mother and her three children with an autosomal dominant mode of inheritance and one of the children with nephropathy, the fifth a sporadic case also with renal involvement. The main findings common to these five patients are symptoms and signs simulating arthritis of the wrists and/or ankles starting at a young age and mimicking juvenile idiopathic arthritis. Early signs of osteolysis and shortening of the carpus or tarsus are radiological characteristic. The disease may be associated with a peculiar face, but most importantly with nephropathy. The pathogenesis is still unknown. CONCLUSION: Recognition of this disease and differentiation from juvenile idiopathic arthritis is important to avoid unnecessary investigations and treatment. Follow-up of renal function is indicated.
Asunto(s)
Artritis Juvenil/diagnóstico , Síndrome de Hajdu-Cheney/diagnóstico , Tobillo/patología , Preescolar , Diagnóstico Diferencial , Femenino , Síndrome de Hajdu-Cheney/genética , Humanos , Lactante , Masculino , Hermanos , Huesos Tarsianos/patología , Muñeca/patologíaRESUMEN
OBJECTIVE: To investigate the involvement of proinflammatory and destructive mediators in oncostatin M (OSM)-induced joint pathology, using gene-deficient mice. METHODS: An adenoviral vector expressing murine OSM was injected into the joints of naive wild-type mice and mice deficient for interleukin-1 (IL-1), IL-6, tumor necrosis factor alpha (TNFalpha), or inducible nitric oxide synthase (iNOS). Reverse transcription-polymerase chain reaction was used to study gene expression. Inflammation and cartilage proteoglycan (PG) depletion were assessed by histology. OSM and IL-1 levels in synovial fluid from patients with juvenile idiopathic arthritis (JIA) were measured by enzyme-linked immunosorbent assay. RESULTS: Adenoviral expression of murine OSM led to joint inflammation, bone apposition, chondrophyte formation, articular cartilage PG depletion, and VDIPEN neoepitope expression in wild-type mice. A unique and consistent observation was the focal PG depletion and disorganization of the growth plate cartilage during the first week of inflammation. Synovial IL-1beta, IL-6, TNFalpha, and iNOS gene expression was strongly induced. Of these factors, only deficiency in IL-1 markedly reduced inflammation and PG depletion and completely prevented growth plate damage. In addition, this is the first study in which OSM was detected in JIA synovial fluid. Most samples were also IL-1beta positive. CONCLUSION: IL-1, but not IL-6, TNFalpha, or iNOS, plays an important role in joint disease induced by intraarticular gene transfer of OSM in mice. The effect of OSM on murine connective tissue and the presence of OSM in human synovial fluid make involvement of OSM in human arthropathies very likely.
Asunto(s)
Adenoviridae/genética , Artritis Juvenil/patología , Placa de Crecimiento/patología , Péptidos/genética , Adolescente , Animales , Artritis Juvenil/metabolismo , Niño , Modelos Animales de Enfermedad , Femenino , Técnicas de Transferencia de Gen , Vectores Genéticos , Humanos , Interleucina-1/deficiencia , Interleucina-1/genética , Interleucina-1/metabolismo , Articulaciones/metabolismo , Articulaciones/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Oncostatina M , Péptidos/metabolismo , Proteoglicanos/metabolismo , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Líquido Sinovial/metabolismoRESUMEN
OBJECTIVE: To describe radiologic features of patients with juvenile idiopathic arthritis (JIA) in a standardized manner, to test the reliability and feasibility of this description, and to correlate these features with clinical signs as a first step in the development of a standardized assessment method. METHODS: The placebo-controlled study of sulfasalazine in patients with oligoarticular, extended oligoarticular, and polyarticular JIA performed by the Dutch Juvenile Idiopathic Arthritis Study Group yielded the data for this study. All trial entry radiographs (clinically involved joints and contralateral joints) were scored (in consensus by a skeletal radiologist and pediatric rheumatologist) for the presence of swelling, osteopenia, joint space narrowing, growth abnormalities, subchondral bone cysts, erosions, and malalignment. RESULTS: Data on 67 of 69 patients were analyzed. The mean age was 9.1 years (range 2.5-17.6 years), and the median disease duration was 24 months (range 5-176 months). Thirteen percent of the patients were IgM rheumatoid factor (IgM-RF) positive, and 16% were HLA-B27 positive. All 68 clinically evaluated joints were included in the maximum of 19 radiographed joints (or joint groups) per patient. The mean number of radiographed joints per patient was 7 (range 2-15); knees, hands, ankles, and feet were most frequently affected. Fifty-eight patients (87%) had radiologic abnormalities in at least one joint (soft-tissue swelling in 63% of patients, growth disturbances in 48%, joint space narrowing in 28%, and erosions in 15%). In total, half of the radiographs of the clinically involved joints showed radiologic abnormalities, including two-thirds of the radiographs of the clinically affected hands and knees. Univariate analysis revealed a good correlation between the overall articular (clinical) severity and the presence of radiologic abnormalities (odds ratio [OR] 1.38, P < 0.0001). Multivariate analysis showed increased ORs for the presence of radiologic abnormalities and IgM-RF positivity (OR 4.6, P = 0.005) or HLA-B27 positivity (OR 3.0, P = 0.004). In general, reproducibility of the radiologic scoring method was good (mean kappa coefficient of 0.74 [range 0.40-0.86]), although there were scoring discrepancies for swelling, osteopenia, and growth disturbances. The scoring took 10-20 minutes per patient. CONCLUSION: Our model of describing and scoring radiologic abnormalities of radiographed joints in JIA was feasible, mostly reproducible, correlated well with the overall articular severity score, and added substantial new information not available on clinical examination.
Asunto(s)
Artritis Juvenil/diagnóstico por imagen , Artrografía/métodos , Adolescente , Antirreumáticos/administración & dosificación , Artritis Juvenil/tratamiento farmacológico , Artrografía/normas , Niño , Preescolar , Femenino , Articulaciones de los Dedos/diagnóstico por imagen , Humanos , Masculino , Reproducibilidad de los Resultados , Índice de Severidad de la Enfermedad , Sulfasalazina/administración & dosificación , Factores de TiempoRESUMEN
Production of immunosuppressive factors is one of the mechanisms by which tumors evade immunosurveillance. Soluble factors hampering dendritic cell (DC) development have recently been identified in culture supernatants derived from tumor cell lines. In this study, we investigated the presence of such factors in 24-h culture supernatants from freshly excised solid human tumors (colon, breast, renal cell carcinoma, and melanoma). While primary tumor-derived supernatant (TDSN) profoundly hampered the in vitro DC differentiation from CD14(+) plastic-adherent monocytes or CD34(+) precursors (based on morphology and CD1a/CD14 phenotype), the effects of tested tumor cell line-derived supernatants were minor. Cyclooxygenase (COX)-1- and COX-2-regulated prostanoids present in the primary TDSN were found to be solely responsible for the observed hampered differentiation of monocyte-derived DC (MoDC). In contrast, both prostanoids and IL-6 were found to contribute to the TDSN-induced inhibition of DC differentiation from CD34(+) precursor cells. While the addition of TDSN during differentiation interfered with the ability of CD34-derived DC to stimulate a primary allogeneic T cell response, it actually increased this ability of MoDC. These opposite effects were correlated to different effects of the TDSN on the expression levels of CD86 and HLA-DR on the DC from the different precursor origins. Although TDSN increased the T cell-stimulatory capacity of MoDC, TDSN inhibited the IL-12 production and increased the IL-10 production of MoDC, thus skewing them to a type-2 T cell-inducing phenotype. In conclusion, this study demonstrates that primary tumors negatively impact DC development and function through COX-1 and -2 regulated factors, whereas tumor-derived cell lines may lose this ability upon in vitro propagation.