RESUMEN
PURPOSE: Histiocytic necrotizing lymphadenitis (HNL) is an inflammatory disease of unknown etiology clinically characterized by painful lymphadenopathy. This study aimed to investigate the role of interferon (IFN)-α in the pathogenesis of HNL and the clinical significance of serum IFN-α levels for the diagnosis and monitoring of HNL disease activity. METHODS: This study enrolled 47 patients with HNL and 43 patients with other inflammatory diseases that require HNL differentiation including malignant lymphoma (ML), bacterial lymphadenitis, and Kawasaki disease. Expression of IFN-stimulated genes (ISGs) and MX1 in the lymph nodes was measured by real-time quantitative reverse transcription polymerase chain reaction and immunofluorescence staining, respectively. Enzyme-linked immunosorbent assay was used to quantify serum cytokine levels. The results were compared with the clinical features and disease course of HNL. RESULTS: Patients with HNL had a significantly elevated ISG expression in the lymph nodes compared with those with ML. MX1 and CD123, a specific marker of plasmacytoid dendritic cells (pDCs), were colocalized. In patients with HNL, serum IFN-α levels were significantly elevated and positively correlated with disease activity. The serum IFN-α level cutoff value for differentiating HNL from other diseases was 11.5 pg/mL. CONCLUSION: IFN-α overproduction from pDCs may play a critical role in HNL pathogenesis. The serum IFN-α level may be a valuable biomarker for the diagnosis and monitoring of disease activity in patients with HNL.
Asunto(s)
Células Dendríticas , Linfadenitis Necrotizante Histiocítica , Interferón-alfa , Ganglios Linfáticos , Humanos , Linfadenitis Necrotizante Histiocítica/diagnóstico , Linfadenitis Necrotizante Histiocítica/sangre , Linfadenitis Necrotizante Histiocítica/inmunología , Masculino , Interferón-alfa/sangre , Femenino , Niño , Adolescente , Adulto , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Preescolar , Ganglios Linfáticos/patología , Proteínas de Resistencia a Mixovirus/genética , Proteínas de Resistencia a Mixovirus/metabolismo , Proteínas de Resistencia a Mixovirus/sangre , Adulto Joven , Persona de Mediana Edad , Linfoma/diagnóstico , Linfoma/inmunología , Linfoma/sangre , Síndrome Mucocutáneo Linfonodular/diagnóstico , Síndrome Mucocutáneo Linfonodular/inmunología , Síndrome Mucocutáneo Linfonodular/sangre , Biomarcadores/sangre , Citocinas/sangre , Citocinas/metabolismoRESUMEN
OBJECTIVES: To investigate the clinical significance of serum cytokine profiles for differentiating between Kawasaki disease (KD) and its mimickers. METHODS: Patients with KD, including complete KD, KD shock syndrome (KDSS), and KD with macrophage activation syndrome (KD-MAS), and its mimickers, including multisystem inflammatory syndrome in children, toxic shock syndrome, and Yersinia pseudotuberculosis infection, were enrolled. Serum levels of interleukin (IL)-6, soluble tumor necrosis factor receptor type II (sTNF-RII), IL-10, IL-18, and chemokine (C-X-C motif) ligand 9 (CXCL9) were measured using enzyme-linked immunosorbent assay and compared them with clinical manifestations. RESULTS: Serum IL-6, sTNF-RII, and IL-10 levels were significantly elevated in patients with KDSS. Serum IL-18 levels were substantially elevated in patients with KD-MAS. Patients with KD-MAS and KD mimickers had significantly elevated serum CXCL9 levels compared with those with complete KD. Area under the receiver operating characteristic curve analysis showed that serum IL-6 was the most useful for differentiating KDSS from the others, IL-18 and CXCL9 for KD-MAS from complete KD, and CXCL9 for KD mimickers from complete KD and KD-MAS. CONCLUSION: Serum cytokine profiles may be useful for differentiating between KD and its mimickers.
Asunto(s)
Citocinas , Síndrome Mucocutáneo Linfonodular , Choque Séptico , Síndrome de Respuesta Inflamatoria Sistémica , Infecciones por Yersinia pseudotuberculosis , Síndrome Mucocutáneo Linfonodular/sangre , Síndrome Mucocutáneo Linfonodular/diagnóstico , Citocinas/sangre , Humanos , Interleucina-6/sangre , Quimiocina CXCL9/sangre , Síndrome de Activación Macrofágica/sangre , Síndrome de Activación Macrofágica/diagnóstico , Masculino , Femenino , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Diagnóstico Diferencial , Choque Séptico/sangre , Choque Séptico/diagnóstico , Infecciones por Yersinia pseudotuberculosis/sangre , Infecciones por Yersinia pseudotuberculosis/diagnóstico , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Síndrome de Respuesta Inflamatoria Sistémica/diagnósticoRESUMEN
Early-onset neonatal infection caused by Streptococcus pneumoniae occurs rarely but has a high mortality rate. Due to the low detection rate of S. pneumoniae in maternal vaginal cultures, administering prophylactic antibiotics for S. pneumoniae to mothers before delivery is challenging. Herein, we present the case of a male newborn who was born at 38 weeks of gestation. The vaginal cultures of his mother before delivery did not reveal the presence of group B streptococcus (GBS) and S. pneumoniae. The newborn experienced respiratory distress six hours after birth and was diagnosed with congenital pneumonia. He was successfully treated with an artificial ventilator and antibiotics. The nasal cavity, external ear canal, and transtracheal tube sputum cultures of the neonate and the vaginal cultures of his mother were positive for S. pneumoniae serotype 3. This case indicates the occurrence of congenital S. pneumoniae infection as a result of intrapartum infection and highlights the necessity to consider S. pneumoniae as a causative agent of early-onset neonatal infection.
RESUMEN
Clinical features, brain magnetic resonance imaging findings and EDSS scores of 11 patients with neurodegenerative central nervous system Langerhans cell histiocytosis were analyzed in Japan. All patients initially had multi-system-type Langerhans cell histiocytosis; 8 at 1-2 years of age and 3 at a later age. Neurodegenerative central nervous system Langerhans cell histiocytosis disease developed after a median time interval of 3.9 years from initial diagnosis. With a median follow-up of 4.5 years, 6 patients showed progression of disease with an EDSS score >3. This study demonstrates the importance of early detection of neurodegenerative central nervous system Langerhans cell histiocytosis by brain magnetic resonance imaging, particularly in the follow-up of patients who developed multi-system-type Langerhans cell histiocytosis in early infancy.
Asunto(s)
Encéfalo/patología , Histiocitosis de Células de Langerhans/complicaciones , Imagen por Resonancia Magnética , Enfermedades Neurodegenerativas/etiología , Adolescente , Edad de Inicio , Cerebelo/patología , Cerebro/patología , Preescolar , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Histiocitosis de Células de Langerhans/epidemiología , Histiocitosis de Células de Langerhans/patología , Humanos , Lactante , Japón/epidemiología , Masculino , Enfermedades Neurodegenerativas/epidemiología , Enfermedades Neurodegenerativas/patología , Puente/patología , Sistema de Registros/estadística & datos numéricos , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: In rare cases, patients with Langerhans cell histiocytosis (LCH) develop neurodegenerative CNS disease (ND-CNS-LCH). Management of ND-CNS-LCH has not been established. METHODS: We treated five pediatric patients with a combination of intravenous immunoglobulin (IVIG) and chemotherapy (steroid +/- vinblastine +/- 6-mercaptopurine +/- methotrexate). Prior to the therapy, three of the five patients had cerebellar ataxia while the remaining two had abnormal MRI findings without apparent neurological deficits. IVIG was given monthly or twice monthly at the dosage of 250-400 mg/kg/dose. RESULTS: The four patients administered more than 23 doses of IVIG and chemotherapy remained in a stable condition and did not show significant progression signs in neurological deficits or brain MRI findings during the 30-month follow-up period (median; range: 19+ to 38+) following the initiation of therapy for ND-CNS-LCH. CONCLUSION: The IVIG-containing treatment may be promising for ND-CNS-LCH; however, its effectiveness remains to be further tested in more patients as well as in a randomized trial.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Histiocitosis de Células de Langerhans/tratamiento farmacológico , Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Enfermedades Neurodegenerativas/tratamiento farmacológico , Niño , Preescolar , Terapia Combinada , Histiocitosis de Células de Langerhans/patología , Humanos , Inmunoglobulinas Intravenosas/administración & dosificación , Factores Inmunológicos/administración & dosificación , Masculino , Mercaptopurina/administración & dosificación , Metotrexato/administración & dosificación , Enfermedades Neurodegenerativas/patología , Vinblastina/administración & dosificaciónRESUMEN
We report a one-year-old boy with early-onset myoclonic epilepsy, developmental arrest, and hyperekplexia during early infancy. He presented with refractory myoclonic/tonic seizures since birth. Electroencephalography revealed multifocal spikes, and rhythmic activities that occurred simultaneous with aggravation of myoclonus accompanied by tonic upper limb elevation. Brain magnetic resonance imaging revealed progressive cerebral atrophy with periventricular signal change and thin corpus callosum at one year of age. A de novo heterozygous missense mutation in the CACNA1A gene was confirmed. This patient was the most severe phenotype of CACNA1A-related early-onset encephalopathy among previous reports.
Asunto(s)
Encéfalo/diagnóstico por imagen , Canales de Calcio/genética , Epilepsias Mioclónicas/diagnóstico por imagen , Epilepsias Mioclónicas/genética , Mutación Missense , Encéfalo/fisiopatología , Epilepsias Mioclónicas/fisiopatología , Humanos , Hiperekplexia/diagnóstico por imagen , Hiperekplexia/genética , Hiperekplexia/fisiopatología , Lactante , Masculino , Fenotipo , Índice de Severidad de la EnfermedadRESUMEN
Although most patients with spinal muscular atrophy (SMA) are homozygous for deletion of the SMN1 gene, some patients bear one SMN1 copy with a subtle mutation. Detection of such an intragenic mutation may be helpful not only in confirming diagnosis but also in elucidating functional domains of the SMN protein. In this study, we identified a novel mutation in SMN1 of two Japanese patients with type I SMA. DHPLC and sequencing analysis revealed that they harbored a point mutation in SMN1 exon 3, 275G > C, leading to tryptophan-to-serine substitution at amino acid 92 (W92S) at the Nterminal of SMN Tudor domain. In-vitro protein binding assays showed that the mutation severely reduced interaction of the domain with SmB protein and fibrillarin, suggesting that it impairs the critical function of SMN. In conclusion, we reported here that a novel mutation, W92S, in the Tudor domain affects the interaction of SMN with the target proteins.
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Sustitución de Aminoácidos , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/genética , Proteínas del Tejido Nervioso/genética , Proteínas de Unión al ARN/genética , Atrofias Musculares Espinales de la Infancia/genética , Niño , Preescolar , Cromatografía Líquida de Alta Presión , Proteínas Cromosómicas no Histona/metabolismo , Análisis Mutacional de ADN/métodos , Salud de la Familia , Femenino , Humanos , Masculino , Ensayo de Unión Radioligante/métodos , Proteínas del Complejo SMN , Serina/genética , Proteína 1 para la Supervivencia de la Neurona Motora , Triptófano/genéticaRESUMEN
The follow-up of eight Japanese children with Langerhans cell histiocytosis (LCH)-related neurodegenerative central nervous system (ND-CNS) disease who were treated with intravenous immunoglobulin (IVIG) for >3 years is described. The patients developed ND-CNS disease at a median age of 5.2 (range 3.5-10.0) years and received IVIG treatment for a median duration of 6.5 + (range 3.7 to 10+) years. After a median follow-up period of 11.6 + (8.3+ to 13.9+) years after ND-CNS disease diagnosis, the median Expanded Disability Status Scale (EDSS) score of the eight patients was 4.0 (range 2.0-9.5). At the last follow-up as of March 2014, three patients have low EDSS scores (<3.0) and can walk without any assistance. Another three patients have EDSS scores of 3.5-4.5 and can walk by themselves, albeit occasionally with supports. However, the remaining two patients are wheelchair bound or bed ridden. The school performance of seven of the eight patients was below average. IVIG appeared to be most beneficial when it was administered soon after ND-CNS disease diagnosis when the EDSS scores were low (1.0-2.5). The patients who began receiving IVIG when their high EDSS scores were higher (4.5-7.0) appeared to obtain less benefit. To prevent progression of ND-CNS disease in patients with LCH, it is recommended to introduce IVIG early and to continue this therapy for >3 years.
Asunto(s)
Histiocitosis de Células de Langerhans/complicaciones , Inmunoglobulinas Intravenosas/uso terapéutico , Enfermedades Neurodegenerativas/tratamiento farmacológico , Enfermedades Neurodegenerativas/etiología , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Enfermedades Neurodegenerativas/diagnóstico , Resultado del TratamientoRESUMEN
We report and discuss a case of Kimura's disease with an unusual eosinophilic epithelioid granulomatous reaction. A 3-year-old Japanese boy with eosinophilia and a high concentration of IgE developed lymphadenopathy and multiple cervical masses. A lymph node biopsy demonstrated the infiltration of eosinophils in the stroma, which is consistent with the findings of Kimura's disease. Interestingly, a number of apoptotic eosinophils was detected in the infiltrating eosinophils. Multiple epithelioid granulomas with central eosinophilic abscesses and necrosis were also observed. Macrophages and giant cells had phagocytosed the apoptotic eosinophils at the edge of the granulomas. In situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay showed that the TUNEL-positive eosinophils were both in the macrophages and in the central eosinophilic abscesses of the granulomas. These findings suggest that the eosinophils had undergone an accelerated apoptosis in this case of Kimura's disease, and that the epithelioid granulomas were produced by phagocytosis of the apoptotic eosinophils by macrophages.
Asunto(s)
Hiperplasia Angiolinfoide con Eosinofilia/patología , Apoptosis , Granuloma Eosinófilo/patología , Eosinófilos/patología , Células Epitelioides/patología , Hiperplasia Angiolinfoide con Eosinofilia/complicaciones , Hiperplasia Angiolinfoide con Eosinofilia/metabolismo , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Preescolar , Granuloma Eosinófilo/complicaciones , Granuloma Eosinófilo/metabolismo , Eosinófilos/metabolismo , Células Epitelioides/metabolismo , Humanos , Técnicas para Inmunoenzimas , Inmunoglobulina E/sangre , Etiquetado Corte-Fin in Situ , Ganglios Linfáticos/metabolismo , Ganglios Linfáticos/patología , Enfermedades Linfáticas/etiología , Enfermedades Linfáticas/metabolismo , Enfermedades Linfáticas/patología , MasculinoRESUMEN
The pathogenetic mechanisms of the central nervous system (CNS) problems associated with Langerhans cell histiocytosis (LCH) are not well established. Effective treatment strategies for these CNS complications are not yet available, while diabetes insipidus, also associated with LCH, can be managed effectively. Three Japanese boys with LCH who developed cerebellar ataxia were evaluated. Similar pediatric cases from the literature are also discussed. All three patients initially developed multifocal LCH lesions during early childhood (age <3 years) that responded well to chemotherapy; however, two of the three patients later developed diabetes insipidus. Ataxia, associated with mild developmental delay, was noted in the patients between the ages of 4 to 8 years. Analysis of these three cases, along with previously reported cases, indicates that the median age of onset of LCH was 2.5 (range 0.1-6.5) years and the median age of onset of cerebellar lesions/ataxia was 7 (range 3.5-16.5) years. Although the incidence of cerebellar LCH involvement is low, delayed onset of CNS disease must be monitored during follow-up care of pediatric LCH patients. Brain magnetic resonance imaging is strongly recommended for early detection of cerebellar lesions, but it remains to be determined whether there are any therapeutic measures to prevent exacerbation of CNS disease.