RESUMEN
BACKGROUND: The risk for amenorrhea following treatment of systemic lupus erythematosus (SLE) patients with low-dose intravenous cyclophosphamide (IVCY) has not been fully explored. Our objective was to ascertain the incidence of amenorrhea following treatment with low-dose IVCY and the association between amenorrhea and the clinical parameters of SLE. METHODS: A case-control retrospective study of premenopausal women ≤ 45 years old who had been treated for SLE with low-dose IVCY (500 mg/body/pulse) plus high-dose glucocorticoids (0.8-1.0 mg/kg/day of prednisolone; IVCY group) or glucocorticoids alone (0.8-1.0 mg/kg/day of prednisolone; steroid group) in our hospital from 2000 through 2009 was conducted using a questionnaire survey and medical record review. RESULTS: Twenty-nine subjects in the IVCY group and 33 subjects in the steroid group returned the questionnaire. A multivariate analysis revealed that age at initiation of treatment ≥ 40 years old was significantly associated with amenorrhea [p = 0.009; odds ratio (OR) 10.2; 95% confidence interval (CI) 1.8-58.7]. IVCY treatment may display a trend for association with amenorrhea (p = 0.07; OR 2.9; 95% CI 0.9-9.4). Sustained amenorrhea developed in 4 subjects in the IVCY group and 1 subject in the steroid group; all of these patients were ≥ 40 years old. Menses resumed in all subjects < 40 years old, irrespective of treatment. CONCLUSIONS: Although low-dose IVCY may increase the risk for amenorrhea, our data suggest that patients < 40 years old have a minimum risk for sustained amenorrhea with low-dose IVCY treatment. A higher risk for sustained amenorrhea following treatment with IVCY is a consideration for patients ≥ 40 years old.
Asunto(s)
Amenorrea/inducido químicamente , Ciclofosfamida/efectos adversos , Inmunosupresores/efectos adversos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Adolescente , Adulto , Factores de Edad , Amenorrea/epidemiología , Estudios de Casos y Controles , Ciclofosfamida/administración & dosificación , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Glucocorticoides/efectos adversos , Humanos , Inmunosupresores/administración & dosificación , Inyecciones Intravenosas , Lupus Eritematoso Sistémico/complicaciones , Persona de Mediana Edad , Prednisolona/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Encuestas y Cuestionarios , Tokio , Adulto JovenRESUMEN
BACKGROUND: Previous studies of magnetic resonance imaging (MRI) as a diagnostic tool for central nervous system (CNS) syndromes in systemic lupus erythematosus (SLE) contained several limitations such as study design, number of enrolled patients, and definition of CNS syndromes. We overcame these problems and statistically evaluated the diagnostic values of abnormal MRI signals and their chronological changes in CNS syndromes of SLE. METHODS: We prospectively studied 191 patients with SLE, comparing those with (n = 57) and without (n = 134) CNS syndrome. CNS syndromes were characterized using the American College of Rheumatology case definitions. RESULTS: Any abnormal MRI signals were more frequently observed in subjects in the CNS group (n = 25) than in the non-CNS group (n = 32) [relative risk (RR), 1.7; 95% confidence interval (CI), 1.1-2.7; p = 0.016] and the positive and negative predictive values for the diagnosis of CNS syndrome were 42% and 76%, respectively. Large abnormal MRI signals (ø >or= 10 mm) were seen only in the CNS group (n = 7; RR, 3.7; CI, 2.9-4.7; p = 0.0002), whereas small abnormal MRI signals (ø < 10 mm) were seen in both groups with no statistical difference. Large signals always paralleled clinical outcome (p = 0.029), whereas small signals did not (p = 1.000). CONCLUSIONS: Abnormal MRI signals, which showed statistical associations with CNS syndrome, had insufficient diagnostic values. A large MRI signal was, however, useful as a diagnostic and surrogate marker for CNS syndrome of SLE, although it was less common.
Asunto(s)
Sistema Nervioso Central/patología , Sistema Nervioso Central/fisiopatología , Errores Diagnósticos/prevención & control , Vasculitis por Lupus del Sistema Nervioso Central/diagnóstico , Vasculitis por Lupus del Sistema Nervioso Central/fisiopatología , Imagen por Resonancia Magnética/normas , Adolescente , Adulto , Anciano , Biomarcadores , Encéfalo/patología , Encéfalo/fisiopatología , Niño , Estudios de Cohortes , Diagnóstico Diferencial , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Fibras Nerviosas Mielínicas/patología , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
Lupus profundus is a rare lupus-specific skin lesion with skin biopsies exhibiting lobular lymphocytic infiltration and destruction of subcutaneous fat tissue. In this report, a CT scan was effective in demonstrating both the presence and the extent of inflammation of lupus profundus in two patients with systemic lupus erythematosus (SLE). Case 1 was a 30-year-old woman developing erythema with subcutaneous induration on the upper arms during the quiescent phase of SLE. A skin biopsy confirmed a diagnosis of lupus profundus. A CT scan of the right upper arm demonstrated a high density area (HDA) of the subcutis under the erythema: a finding consistent with lupus profundus. Case 2 was a 28-year-old woman recently diagnosed with SLE. She also developed a skin ulcer on the right hip. A CT scan of the hip revealed an HDA and lipoatrophy of the subcutis around the ulcer: these findings were compatible with lupus profundus. Treatment with high-dose prednisolone improved the illness in the both cases. A CT scan is a useful and convenient imaging modality for confirming the diagnosis of lupus profundus.
Asunto(s)
Lupus Eritematoso Sistémico/diagnóstico por imagen , Paniculitis de Lupus Eritematoso/diagnóstico por imagen , Tomografía Computarizada por Rayos X/estadística & datos numéricos , Adulto , Diagnóstico Diferencial , Femenino , Humanos , Lupus Eritematoso Sistémico/complicaciones , Paniculitis de Lupus Eritematoso/complicacionesRESUMEN
OBJECTIVE: To clarify the clinical features of patients with systemic sclerosis (SSc) who developed severe gastrointestinal tract (GIT) involvement in the early stage of the disease. METHODS: Three hundred two consecutive Japanese patients with SSc were investigated: Group 1 comprised 14 patients with severe GIT involvement (malabsorption syndrome and/or pseudo-obstruction) within 2 years of onset of SSc; group 2 consisted of all patients without severe GIT involvement (n = 288); and group 3 consisted of 117 patients without severe GIT involvement within 2 years of onset of SSc. Autoantibodies were evaluated using double immunodiffusion, ELISA, and immunoprecipitation. RESULTS: We found significant differences in clinical features among the 3 groups. Diffuse cutaneous type, erosive esophagitis, and myositis were more common in group 1 than in group 2 (p = 0.007, 0.003, and 0.003, respectively) or group 3 (p = 0.04, 0.002, and 0.01, respectively), whereas interstitial lung disease (ILD) was more frequent in group 2 (p = 0.005) and group 3 (p = 0.02) versus group 1. Antinuclear antibodies showed a nucleolar pattern significantly more frequently in group 1. Myositis-related autoantibodies, including anti-U1RNP, anti-U3RNP, anti-Ku, and anti-signal recognition particle antibodies, were observed in 57% of group 1. CONCLUSION: Our findings strongly suggest the existence of a subgroup of SSc patients with severe GIT involvement in the early stage. Among the Japanese individuals, these patients never developed severe ILD, even though they were classified as having diffuse cutaneous SSc.
Asunto(s)
Tracto Gastrointestinal/patología , Esclerodermia Sistémica/patología , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Antinucleares/inmunología , Autoanticuerpos/inmunología , Femenino , Humanos , Japón , Persona de Mediana Edad , Esclerodermia Sistémica/inmunología , Esclerodermia Sistémica/fisiopatologíaRESUMEN
OBJECTIVE: Acute confusional state (ACS) is an uncommon but severe central nervous system (CNS) syndrome in systemic lupus erythematosus (SLE) defined by clinical manifestations. To develop useful and reliable diagnostic tools for ACS, we evaluated the association of cerebral spinal fluid (CSF) tests with ACS and their predictive values for the diagnosis of ACS in SLE. METHODS: We performed a prospective study using a cohort of 59 patients with SLE and compared those with and without ACS. Associations between ACS and each CSF test [interleukin 6 (IL-6), IL-8, interferon-alpha, IgG index, and Q-albumin] were statistically evaluated. Each patient underwent all CSF evaluations. RESULTS: ACS was diagnosed in 10 patients (ACS group), SLE-related CNS syndromes except ACS in 13, and no CNS syndromes in 36 (non-CNS group). CSF IL-6 levels in the ACS group were significantly higher than those in the non-CNS group (p < 0.05). A positive IgG index (p = 0.028) was significantly associated with ACS. No other test showed a significant association with ACS. The positive and negative predictive values for the diagnosis of ACS in SLE were 80% and 85% for elevated CSF IL-6 levels (> or = 31.8 pg/ml), and 75% and 83% for the IgG index, respectively. CONCLUSION: No single CSF test had sufficient predictive value to diagnose ACS in SLE, although CSF IL-6 levels and the IgG index showed statistical associations with ACS. Use of CSF tests combined with careful history and clinical examinations is recommended for proper diagnosis of ACS in SLE.
Asunto(s)
Delirio , Lupus Eritematoso Sistémico , Adolescente , Adulto , Estudios de Cohortes , Delirio/líquido cefalorraquídeo , Delirio/diagnóstico , Delirio/etiología , Femenino , Humanos , Interferón-alfa/líquido cefalorraquídeo , Interleucina-6/líquido cefalorraquídeo , Interleucina-8/líquido cefalorraquídeo , Lupus Eritematoso Sistémico/líquido cefalorraquídeo , Lupus Eritematoso Sistémico/complicaciones , Masculino , Persona de Mediana Edad , Valor Predictivo de las PruebasRESUMEN
The aberrant production of precursor IL-1alpha (pre-IL-1alpha) in skin fibroblasts that are derived from systemic sclerosis (SSc) is associated with the induction of IL-6 and procollagen, which contributes to the fibrosis of SSc. However, little is understood about how intracellular pre-IL-1alpha regulates the expression of the other molecules in fibroblasts. We report here that pre-IL-1alpha can form a complex with IL-1alpha-binding proteins that is translocated into the nuclei of fibroblasts. Immunoprecipitation that used anti-human IL-1alpha Ab and (35)S-labeled nuclear extracts of fibroblasts showed three specific bands (approximately equal to 31, 35, and 65 kDa). The 31-kDa molecule was identified as pre-IL-1alpha, and the 35- and 65-kDa molecules might be pre-IL-1alpha-binding proteins. A partial sequencing for the 10 aa from the N-terminals of the molecules showed 100% homology for HAX-1 (HS1-associated protein X-1) and IL-1 receptor type II (IL-1RII). Suppression of the genes of HAX-1 or IL-1RII induced the inhibitory effects of IL-1 signal transduction, including production of IL-6 and procollagen, by fibroblasts. In particular, pre-IL-1alpha was not translocated into the nucleus by an inhibition of HAX-1. These findings reveal that nuclear localization of pre-IL-1alpha depends on the binding to HAX-1 and that biological activities might be elicited by the binding to both HAX-1 and IL-1RII in SSc fibroblasts.