RESUMEN
Coronavirus disease 2019 (COVID-19) in children can be compounded by concurrent diseases and immunosuppressants. For the first time, we aimed to report the clinical features of concurrent COVID-19 and pediatric rheumatic disease (PRD) in Japan. Pediatric Rheumatology Association of Japan members were surveyed between 1 April 2020 and 31 August 2022. Outcome measurements included the clinical features of concurrent PRD and COVID-19. Questionnaire responses were obtained from 38 hospitals. Thirty-one hospitals (82%) had children with PRD and COVID-19. The female-to-male ratio in these children (n = 156) was 7:3, with half aged 11-15 years. The highest proportion of children with PRD and COVID-19 was accounted for by juvenile idiopathic arthritis (52%), followed by systemic lupus erythematosus (24%), juvenile dermatomyositis (5%), scleroderma (4%), and Takayasu arteritis (3%). Of children with PRD, a significant majority (97%) were found to be asymptomatic (10%) or presented with mild symptoms (87%) of the COVID-19 infection. No severe cases or deaths were observed. Regarding the use of glucocorticoids, immunosuppressants, or biologics for PRD treatment before COVID-19, no significant difference was found between asymptomatic/mild and moderate COVID-19 in children with PRD. Therefore, COVID-19 is not a threat to children with PRD in Japan.
Asunto(s)
COVID-19 , Enfermedades Reumáticas , Reumatología , Niño , Humanos , Masculino , Femenino , COVID-19/epidemiología , Enfermedades Reumáticas/diagnóstico , Enfermedades Reumáticas/epidemiología , Enfermedades Reumáticas/tratamiento farmacológico , Japón/epidemiología , Inmunosupresores/uso terapéutico , Encuestas y CuestionariosRESUMEN
OBJECTIVES: To clarify how pediatric rheumatologists treat systemic juvenile idiopathic arthritis (s-JIA) associated macrophage activation syndrome (MAS) in the real world and to assess the efficacy and safety of dexamethasone palmitate (DEX-P) in the treatment of s-JIA-associated MAS. METHODS: This multicenter, retrospective study was conducted at 13 pediatric rheumatology institutes in Japan. This study included 28 patients with s-JIA-associated MAS. Clinical findings, such as treatment details and adverse events, were evaluated. RESULTS: Methylprednisolone (mPSL) pulse therapy was selected as the first-line treatment in more than half of the patients with MAS. Cyclosporine A (CsA) was used as first-line therapy in combination with corticosteroids in half of the patients with MAS. DEX-P and/or CsA were selected as the second-line therapy in 63% of patients with corticosteroid-resistant MAS. Plasma exchange was selected as the third-line therapy for DEX-P and CsA-resistant MAS. All patients improved and there were no characteristically severe adverse events associated with DEX-P. CONCLUSIONS: The first-line treatment for MAS in Japan is mPSL pulse therapy and/or CyA. DEX-P could be an effective and safe therapeutic option for patients with corticosteroid-resistant MAS.
Asunto(s)
Artritis Juvenil , Síndrome de Activación Macrofágica , Niño , Humanos , Artritis Juvenil/tratamiento farmacológico , Síndrome de Activación Macrofágica/tratamiento farmacológico , Estudios Retrospectivos , Japón , Ciclosporina , Corticoesteroides/uso terapéuticoRESUMEN
Short stature is a common clinical condition in paediatric outpatient clinics and is associated with various clinical conditions, ranging from normal variants to severe diseases. Short stature is known to be caused by chronic inflammatory conditions, in which over-produced inflammatory cytokines are reported to be involved in growth suppression. Castleman disease is a rare lymphoproliferative disorder known as a chronic inflammatory disease with overproduction of interleukin 6, which often causes systemic symptoms such as fever, fatigue, weight loss, and night sweats. Here, we report the case of a 10-year-old female diagnosed with unicentric Castleman disease, who presented with short stature as the sole clinical sign but lacked typical systemic symptoms of Castleman disease. An elevated serum C-reactive protein level led us to suspect a chronic inflammatory condition, and we found an intra-abdominal tumour that was histopathologically confirmed as Castleman disease. The tumour removal resulted in a steady catch-up in her height in the six years following the surgery. We also present a brief review of relevant literature on paediatric cases of Castleman disease associated with growth impairment. Clinicians should be aware that chronic inflammatory conditions can cause growth impairment, which may be a key clinical manifestation of such conditions.
Asunto(s)
Enfermedad de Castleman , Femenino , Humanos , Niño , Enfermedad de Castleman/complicaciones , Enfermedad de Castleman/diagnóstico , Estudios de Seguimiento , Diagnóstico Diferencial , FiebreRESUMEN
BACKGROUND: Short bowel syndrome (SBS) is a rare yet costly disease with an incidence rate of 3 per million people. Herein, we report a rare case of eosinophilic gastrointestinal disorders (EGIDs) with SBS after strangulated bowel obstruction. CASE PRESENTATION: A 5-year-old male had a necrotic intestine of 340 cm resected due to strangulated bowel obstruction caused by an intestinal mesenteric hiatal hernia. The length of the residual intestine was 51 cm. Bloody stools appeared 19 days postoperatively. Colonoscopy showed diffuse redness of the colonic mucosa, and pathological findings showed moderate chronic inflammatory cellular infiltration. On blood examination, the eosinophil count was > 30%. EGIDs with short bowel syndrome (SBS) were suspected. Because his symptoms did not improve with initial nutrition therapy, he was transferred to our hospital 5 months after the operation. Prednisolone was administrated at an initial dose of 1.4 mg/kg/day, 6 days after his transfer. Bloody stools disappeared after prednisolone administration. Seven months after discharge, he had no bloody stool recurrence. CONCLUSION: The risk of developing secondary EGIDs in children with SBS should be considered, and postoperative management should include attention to abdominal symptoms and elevated eosinophil counts on blood examination.
RESUMEN
BACKGROUND: Regular assessment of bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) is essential for detecting glucocorticoid-induced osteoporosis in juvenile-onset autoimmune diseases. Z-score is used to standardize osteoporosis assessment in children and is evaluated with only one of three devices in Japan. The purpose of this study was to determine how many Japanese medical facilities for pediatric rheumatic diseases were unable to use Z-scores to evaluate osteoporosis. METHODS: Electronic questionnaires were distributed between 2017 and 2019 to hospitals belonging to the Pediatric Rheumatology Association of Japan and to university hospitals and public children's hospitals that provide medical care for pediatric rheumatic diseases. The questionnaire inquired about the location of DXA measurement, manufacturer (Hologic, GE healthcare, Hitachi), and measurement site, and the answers were collected using Google Forms. Statcel 4 was used for analysis. RESULTS: Overall, 120 facilities responded to the survey, of which 117 had DXA. In the remaining three facilities, DXA was not installed in two and was out of order in one. Bone loss in childhood was evaluated using a Z-score calculated from age-based reference values; however, 30% of hospitals without HOLOGIC DXA could not evaluate osteoporosis by Z-score in Japanese childhood. The characteristics of the hospitals enrolled in this study did not bias the selection of Hologic DXA. CONCLUSIONS: Neighboring institutions should consider sharing access to Hologic DXA equipment, to ensure use of uniform reference values. GE BMD reference values should be established for Japanese children.
Asunto(s)
Absorciometría de Fotón , Equipo para Diagnóstico , Equipos y Suministros de Hospitales , Osteoporosis/diagnóstico , Enfermedades Reumáticas/diagnóstico , Densidad Ósea , Niño , Equipo para Diagnóstico/provisión & distribución , Humanos , Japón/epidemiología , Pediatría , Encuestas y CuestionariosRESUMEN
BACKGROUND: M1-type proinflammatory macrophages (MΦ) promote glomerular injury in lupus nephritis (LN). However, whether this phenotype is altered by steroid therapy is unclear. Therefore, we investigated the effect of steroid treatment on MΦ phenotype in LN. METHODS: Patients with LN (7-18 years old) were divided into 2 groups: those with no treatment (N) before biopsy (n = 17) and those who underwent steroid (S) treatment (3-73 days) before biopsy (n = 15). MΦ number and phenotype were assessed by immunofluorescence. In vitro studies used monocyte-derived MΦ from healthy volunteers. RESULTS: Age at biopsy, urine findings, and kidney function (eGFR) were comparable between the two groups. Biopsies in N group had higher levels of active lesions such as endocapillary hypercellularity, necrosis, and cellular crescent formation (p < 0.05). The total CD68+ MΦ infiltrate was comparable between N and S groups. However, N group had more M1 MΦ (CD68+ CD86+ cells) (p < 0.05) and fewer M2 MΦ (CD68+ CD163+ cells) (p < 0.05), giving a 6-fold increase in the M2/M1 ratio in S vs. N groups. Dexamethasone treatment of cultured MΦ induced upregulation of CD163 expression, increased production of anti-inflammatory (IL-10, IL-19) and profibrotic factors (FGF-22, PDGF), and upregulated the scavenger receptor, stabilin-1. Upregulation of stabilin-1 in CD163+ M2 MΦ was confirmed in biopsies from S group. CONCLUSIONS: Initial steroid treatment induces MΦ phenotypic change from proinflammatory M1 to anti-inflammatory or profibrotic M2 in LN with acute/active lesions. Although steroid treatment is effective for resolution of M1-medated injury, promotion of fibrotic lesions via M2 MΦ is a potential downside of steroid single therapy in LN.
Asunto(s)
Nefritis Lúpica , Macrófagos/fisiología , Adolescente , Antiinflamatorios , Diferenciación Celular , Niño , Humanos , Nefritis Lúpica/tratamiento farmacológico , FenotipoRESUMEN
OBJECTIVES: To collect clinical information and NOD2 mutation data on patients with Blau syndrome and to evaluate their prognosis. METHODS: Fifty patients with NOD2 mutations were analysed. The activity of each NOD2 mutant was evaluated in HEK293 cells by reporter assay. Clinical information was collected from medical records through the attending physicians. RESULTS: The study population comprised 26 males and 24 females aged 0-61 years. Thirty-two cases were sporadic, and 18 were familial from 9 unrelated families. Fifteen different mutations in NOD2 were identified, including 2 novel mutations (p.W490S and D512V); all showed spontaneous nuclear factor kappa B activation, and the most common mutation was p.R334W. Twenty-six patients had fever at relatively early timepoints in the disease course. Forty-three of 47 patients had a skin rash. The onset of disease in 9 patients was recognised after BCG vaccination. Forty-five of 49 patients had joint lesions. Thirty-eight of 50 patients had ocular symptoms, 7 of which resulted in blindness. After the diagnosis of Blau syndrome, 26 patients were treated with biologics; all were antitumour necrosis factor agents. Only 3 patients were treated with biologics alone; the others received a biologic in combination with methotrexate and/or prednisolone. None of the patients who became blind received biologic treatment. CONCLUSIONS: In patients with Blau syndrome, severe joint contractures and blindness may occur if diagnosis and appropriate treatment are delayed. Early treatment with a biologic agent may improve the prognosis.
Asunto(s)
Artritis/tratamiento farmacológico , Artritis/genética , Artritis/patología , Proteína Adaptadora de Señalización NOD2/genética , Sarcoidosis/tratamiento farmacológico , Sarcoidosis/genética , Sarcoidosis/patología , Sinovitis/tratamiento farmacológico , Sinovitis/genética , Sinovitis/patología , Uveítis/tratamiento farmacológico , Uveítis/genética , Uveítis/patología , Adolescente , Adulto , Edad de Inicio , Antirreumáticos/uso terapéutico , Ceguera/epidemiología , Ceguera/etiología , Niño , Preescolar , Femenino , Humanos , Lactante , Japón , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Mutación , Adulto JovenRESUMEN
OBJECTIVES: Mevalonate kinase deficiency (MKD), a rare autosomal recessive autoinflammatory syndrome, is caused by disease-causing variants of the mevalonate kinase (MVK) gene. A national survey was undertaken to investigate clinical and genetic features of MKD patients in Japan. METHODS: The survey identified ten patients with MKD. Clinical information and laboratory data were collected from medical records and by direct interviews with patients, their families, and their attending physicians. Genetic analysis and measurement of MVK activity and urinary excretion of mevalonic acid were performed. RESULTS: None of the 10 patients harbored MVK disease-causing variants that are common in European patients. However, overall symptoms were in line with previous European reports. Continuous fever was observed in half of the patients. Elevated transaminase was observed in four of the 10 patients, two of whom fulfilled the diagnostic criteria for hemophagocytic lymphohistiocytosis. About half of the patients responded to temporary administration of glucocorticoids and NSAIDs; the others required biologics such as anti-IL-1 drugs. CONCLUSION: This is the first national survey of MKD patients in a non-European country. Although clinical symptoms were similar to those reported in Europe, the incidence of continuous fever and elevated transaminase was higher, probably due to differences in disease-causing variants.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Anticuerpos Monoclonales/uso terapéutico , Glucocorticoides/uso terapéutico , Interleucina-1beta/antagonistas & inhibidores , Deficiencia de Mevalonato Quinasa , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Anticuerpos Monoclonales Humanizados , Femenino , Pruebas Genéticas/métodos , Humanos , Factores Inmunológicos/uso terapéutico , Lactante , Japón/epidemiología , Masculino , Deficiencia de Mevalonato Quinasa/diagnóstico , Deficiencia de Mevalonato Quinasa/epidemiología , Deficiencia de Mevalonato Quinasa/genética , Ácido Mevalónico/orina , Encuestas y Cuestionarios , Evaluación de SíntomasRESUMEN
Haemophilus influenzae is a rare cause of peritonitis in patients on peritoneal dialysis (PD). We report a case of peritonitis due to non-typeable H. influenzae in a 5-year-old girl on automated PD. The patient was successfully treated with intraperitoneal cefepime and cefazolin. The isolate was multilocus sequence type 3 and contained the hmw and hia genes but was IS1016-negative. Seven of the eight reported cases were female, indicating that sex-associated factors may be important in H. influenzae peritonitis in patients on PD. Determination of the pathogenesis of PD-associated H. influenzae peritonitis requires gene analysis and a swab sample from the vaginal introitus.
RESUMEN
Henoch-Schönlein purpura nephritis (HSPN) is one of the most common types of chronic glomerulonephritis in children; however, there have been few reports on the pathogenesis and management of grade VI HSPN. We present the case of a 6-year-old boy with grade VI HSPN accompanied by severe nephrotic syndrome and hypocomplementaemia. Immunohistological studies revealed profound glomerular accumulation of CD45- and CD68-positive inflammatory cells. Moreover, some cells expressed the proliferating marker proliferating cell nuclear antigen. His proteinuria and general oedema persisted despite repeated high-dose steroid therapy; however, these clinical symptoms immediately improved after beginning treatment with cyclophosphamide (CyP). Grade VI HSPN was successfully treated with steroids and immunosuppressants. Among immunosuppressive drugs, CyP was considered the most effective.
Asunto(s)
Proliferación Celular/efectos de los fármacos , Ciclofosfamida/uso terapéutico , Glomerulonefritis Membranoproliferativa/tratamiento farmacológico , Vasculitis por IgA/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Riñón/efectos de los fármacos , Leucocitos/efectos de los fármacos , Biopsia , Niño , Quimioterapia Combinada , Técnica del Anticuerpo Fluorescente , Glomerulonefritis Membranoproliferativa/diagnóstico , Glomerulonefritis Membranoproliferativa/inmunología , Glucocorticoides/uso terapéutico , Humanos , Vasculitis por IgA/diagnóstico , Vasculitis por IgA/inmunología , Riñón/inmunología , Riñón/patología , Leucocitos/inmunología , Leucocitos/patología , Masculino , Síndrome Nefrótico/tratamiento farmacológico , Síndrome Nefrótico/inmunología , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND: Prevention of chronic kidney allograft injury (CAI) is a major goal in improving kidney allograft survival; however, the mechanisms of CAI are not clearly understood. The current study investigated whether alternatively activated M2-type macrophages are involved in the development of CAI. METHODS: A retrospective study examined kidney allograft protocol biopsies (at 1 h and at years 1, 5, and 10--a total of 41 biopsies) obtained from 13 children undergoing transplantation between 1991 and 2008 who were diagnosed with CAI: interstitial fibrosis and tubular atrophy (IF/TA) not otherwise specified (IF/TA-NOS). RESULTS: Immunostaining identified a significant increase in interstitial fibrosis with accumulation of CD68 + CD163+ M2-type macrophages. CD163+ cells were frequently localized to areas of interstitial fibrosis exhibiting collagen I deposition and accumulation of α-smooth muscle actin (SMA) + myofibroblasts. There was a significant correlation between interstitial CD163+ cells and the parameters of interstitial fibrosis (p < 0.0001), and kidney function (r =-0.82, p < 0.0001). The number of interstitial CD163+ cells at years 1 and 5 also correlated with parameters of interstitial fibrosis at years 5 and 10 respectively. Notably, urine CD163 levels correlated with interstitial CD163+ cells (r = 0.79, p < 0.01) and parameters of interstitial fibrosis (p < 0.0001). However, CD3+ T lymphocytic infiltration did not correlate with macrophage accumulation or fibrosis. In vitro, dexamethasone up-regulated expression of CD163 and cytokines (TGF-ß1, FGF-2, CTGF) in human monocyte-derived macrophages, indicating a pro-fibrotic phenotype. CONCLUSIONS: Our findings identify a major population of M2-type macrophages in patients with CAI, and suggest that these M2-type macrophages might promote the development of interstitial fibrosis in IF/TA-NOS.
Asunto(s)
Trasplante de Riñón/efectos adversos , Riñón/inmunología , Activación de Macrófagos , Macrófagos/inmunología , Insuficiencia Renal Crónica/inmunología , Adolescente , Adulto , Aloinjertos , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Atrofia , Biomarcadores/metabolismo , Biopsia , Células Cultivadas , Niño , Dexametasona/farmacología , Femenino , Fibrosis , Humanos , Inmunohistoquímica , Inmunosupresores/uso terapéutico , Riñón/metabolismo , Riñón/patología , Activación de Macrófagos/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Fenotipo , Receptores de Superficie Celular/metabolismo , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/metabolismo , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: Tocilizumab (TCZ), an antiinterleukin-6 receptor monoclonal antibody, is clinically beneficial in patients with systemic-onset juvenile idiopathic arthritis (sJIA). We investigated the clinical and radiological outcomes of TCZ therapy in patients with sJIA. METHODS: We retrospectively evaluated 2 clinical trials (NCT00144599 and NCT00144612) involving 40 patients with sJIA who received intravenous TCZ (8 mg/kg) every 2 weeks. Clinical data and radiographs of the hands and large joints were assessed before and during TCZ treatment. The Poznanski score, modified Larsen scores of the hands and large joints, and Childhood Arthritis Radiographic Score of the Hip (CARSH) were recorded. RESULTS: After a mean duration of 4.5 years of TCZ treatment, clinical data had improved significantly, the mean Poznanski score improved from -1.5 to -1.1, the mean Larsen score of the hands deteriorated from 7.0 to 10.0, the mean Larsen score for the large joints deteriorated from 5.9 to 6.8, and the CARSH worsened from 3.9 to 6.2. The Larsen score for the large joints improved in 11 cases (28%), remained unchanged in 8 cases (20%), and worsened in 21 cases (52%). Matrix metalloproteinase 3 (MMP-3) levels remained significantly higher (278 mg/dl) in patients with worsened Larsen scores than in patients with improved or unchanged scores (65 mg/dl). Logistic regression analysis showed that older age at disease onset was a significant risk factor for radiographic progression. CONCLUSION: The modified Larsen score of the large joints deteriorated in half the patients who had high MMP-3 levels during TCZ treatment and who were significantly older at disease onset.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Juvenil/tratamiento farmacológico , Articulaciones de la Mano/diagnóstico por imagen , Articulación de la Cadera/diagnóstico por imagen , Adolescente , Anticuerpos Monoclonales Humanizados/farmacología , Antirreumáticos/farmacología , Artritis Juvenil/diagnóstico por imagen , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Articulaciones de la Mano/efectos de los fármacos , Articulación de la Cadera/efectos de los fármacos , Humanos , Masculino , Radiografía , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
We report 2 cases of diffuse mesangial sclerosis (DMS) accompanied by severe podocyte excretion in urine. Patient 1 was a 9-day-old girl with a WT1 mutation who developed Wilms tumor at 6 months of age and was subsequently diagnosed with Denys-Drash syndrome. Patient 2 was a 1-year-old boy without a WT1 abnormality but presenting with heavy proteinuria. In both patients, histological examination showed findings of DMS. Immunohistochemical staining for synaptopodin (a podocyte marker) revealed a reduced number of podocytes in the glomeruli with severe sclerosis; however, podocytes persisted in the relatively intact glomeruli. Some glomeruli were accompanied by sclerotic lesions surrounded by proliferating cells; immunofluorescence staining revealed a majority of these proliferating cells to be positive for claudin-1 (a parietal cell marker) but negative for synaptopodin. These findings suggest that podocyte loss and the consequent proliferation of parietal cells are common processes in the pathogenesis of DMS.
Asunto(s)
Síndrome de Denys-Drash/patología , Glomérulos Renales/patología , Síndrome Nefrótico/patología , Podocitos/patología , Esclerosis/patología , Tumor de Wilms/patología , Síndrome de Denys-Drash/genética , Síndrome de Denys-Drash/fisiopatología , Femenino , Humanos , Lactante , Recién Nacido , Glomérulos Renales/fisiopatología , Masculino , Síndrome Nefrótico/genética , Síndrome Nefrótico/fisiopatología , Fenotipo , Podocitos/fisiología , Esclerosis/genética , Esclerosis/fisiopatología , Proteínas WT1/genética , Tumor de Wilms/genética , Tumor de Wilms/fisiopatologíaRESUMEN
OBJECTIVE: We investigated the safety and efficacy of administering influenza vaccines to patients with systemic-onset juvenile idiopathic arthritis (sJIA) treated with tocilizumab. PATIENTS AND METHODS: The subjects were 27 sJIA patients treated with tocilizumab and 17 healthy age- and sex-matched volunteers. Serum samples were collected prior to and 4-7 weeks after vaccination. Hemagglutination inhibition values of the vaccine were taken as the antibody titers. The duration of tocilizumab administration and the daily doses of prednisolone per unit body weight were analyzed to identify factors affecting the responses of the sJIA patients to influenza vaccination. We questioned all the subjects about whether they had contracted influenza and whether they had had adverse reactions to the influenza vaccination. We compared steroid doses in sJIA patients before and after vaccination to document any worsening of the underlying disease. RESULTS: The efficacy of influenza vaccination did not differ significantly between the sJIA group and the healthy controls. The duration of tocilizumab administration did not affect the response of the sJIA patients to the influenza vaccination. None of the sJIA patients experienced either severe adverse reactions or disease exacerbation after the influenza vaccination. CONCLUSION: We found that sJIA patients treated with tocilizumab could be effectively and safely immunized with the influenza vaccine.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Artritis Juvenil/tratamiento farmacológico , Vacunas contra la Influenza/efectos adversos , Gripe Humana/prevención & control , Adolescente , Artritis Juvenil/inmunología , Niño , Preescolar , Femenino , Humanos , Vacunas contra la Influenza/inmunología , MasculinoRESUMEN
Systemic-onset juvenile idiopathic arthritis (s-JIA) is a rare inflammatory disease classified as a subtype of chronic childhood arthritis, manifested by spiking fever, erythematous skin rash, pericarditis and hepatosplenomegaly. The genetic background underlying s-JIA remains poorly understood. To detect disease-related copy number variations (CNVs), we performed single-nucleotide polymorphism array analysis in 50 patients with s-JIA. We detected many CNVs, but most of them were inherited from either of normal-phenotype parents. However, in one patient, we could identify two de novo microduplications at 19q13.42 with the size of 77 and 622 kb, separated by a 109-kb segment of normal copy number. The duplications encompass NLRP family (NLRP2, NLRP9 and NLRP11) as well as IL11 and HSPBP1, all of which have an important role in inflammatory pathways. These genes may significantly contribute to the pathogenesis of s-JIA.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , Artritis Juvenil/genética , Duplicación Cromosómica/genética , Cromosomas Humanos Par 19/genética , Familia de Multigenes/genética , Adolescente , Hibridación Genómica Comparativa , Variaciones en el Número de Copia de ADN , Femenino , Regulación de la Expresión Génica , Humanos , Polimorfismo de Nucleótido SimpleRESUMEN
Behçet's disease (BD) is a multisystem immune-mediated inflammatory disorder. The choice of treatments depends on organ involvements and its severity. The treatments for pediatric patients usually consist of corticosteroids and immunosuppressants, but some of them are refractory to these treatments. Recently, tumor necrosis factor alpha (TNF-alpha) appears to play an important role in the immunopathogenesis in BD. We describe two patients with childhood-onset BD, successfully treated by anti-TNF agents. One patient, a 18-year-old male, was diagnosed as having BD at 8 years of age. He developed abdominal pain and bloody diarrhea at 17 years of age. Gastrointestinal endoscopic examination revealed esophageal and ileocolic ulceration consistent with intestinal BD. Methylpredonisolone pulse therapy and immunosuppressants were administrated, but did not respond. Infliximab infusions (4 mg/kg) were given at weeks of 0, 2, 6, and then every 8 weeks. A dramatic improvement in gastrointestinal symptoms and extraintestinal manifestations were observed. Another patient, a 9-year-old girl, developed recurrent oral ulcers and folliculitis at 4 years of age. She was diagnosed as having BD at 6 years of age, and treated with colchicines, corticosteroids and immunosuppressive agents. She was suffering from fever, malaise, and arthralgia in addition to mucocutaneous manifestation. At 8 years of age, etanercept was started at a dosage of 25 mg subcutaneously twice a week. A resolution of the systemic and mucocutaneous symptoms was achieved. Furthermore, she was free from corticosteroids in three months. Anti-TNF therapy would be a good choice for juvenile BD refractory to conventional treatments.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Síndrome de Behçet/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adolescente , Niño , Femenino , Humanos , Infliximab , MasculinoRESUMEN
CINCA/NOMID is an autoinflammatory disorder characterized by the triad of neonatal onset of cutaneous symptoms, chronic meningitis, and recurrent fever and it presents with distinctive osteoarthropathy, synovitis mainly of the large joints and overgrowth of epimetaphyseal cartilage, particularly of the long bones. The cartilage overgrowth eventually causes osseous overgrowth and deformity that persists beyond skeletal maturity and leads to limb length discrepancy, joint contracture, and early degenerative arthropathy. Autoinflammation in CAPS/NOMID has been proven to derive from excessive release of interleukin-1 (IL-1). It has been well documented that the IL-1 receptor antagonist anakinra (Kineret(R)) helps mitigate systemic inflammation in the disorder. However, a general consensus has not been reached on its beneficial effect on osteoarthropathy. The case of a girl with CINCA/NOMID syndrome who showed dramatic improvement of osteoarthropathy after anakinra treatment is reported. A 4-year-old girl suffered at the age of 10 months from a generalized urticarial skin lesion with recurrent episodes of fever and growth disorder. Blood examination revealed persistent massive neutrophilia, anemia and intense acute phase response. She manifested knee joint swelling with limited ROM when she was 20 months old and was diagnosed as being CINCA/NOMID based on characteristic findings of radiograph despite negative CIAS1 mutation. Radiological examination demonstrated metaphyseal fraying and cupping and widening of the growth plate in the distal femur. MR imaging showed mottled gadolinium enhancement at the chondrosseous junction. Neither significant joint effusion nor synovitis was identified. At 2 years and 7 months of age, anakinra, 2 mg/kg/day given by regular daily subcutaneous injections, was started. A few days after the initiation of the treatment, her clinical symptoms and laboratory findings of active inflammation were promptly alleviated. She was not able to walk unaided prior to the treatment, but she walked independently 1 month after the treatment. Follow-up radiographs and MR imaging showed that growth plate widening and gadolinium enhancement at the chondrosseous junction were less conspicuous. Furthermore, longitudinal growth of the femur and tibia was identified during 20 months of observation.
RESUMEN
Takayasu's arteritis (TA) is a chronic idiopathic inflammatory disease affecting primarily aorta and its proximal branches. Pediatric patients with TA tend to have more severe clinical course and be refractory to conventional treatments compared with adults. Corticosteroids are major treatment of TA, however, high dose is required to get remission. Particularly, adolescent patients are usually suffering from side-effects of excessive dose of corticosteroids. Immunosuppressants are added expecting the corticosteroid sparing agents. However, some patients, such as HLA-B52 positive, tend to be registant to these conventional treatments. Recently, several reports showed the efficacy of Infliximab, anti-tumor necrosis factor (TNF) alpha monoclonal antibody, for adult patients with refractory TA. We described three cases of adolescents with TA treated with Infliximab. It was initially effective in all three patients. However, serious infusion reaction occurred in one of them during 11(th) times of Infliximab infusion and she discontinued the therapy. Other two patients showed good response in initial phase, but clinical manifestations and laboratory findings became worse after several months. In these patients with secondary failure to Infliximab, increased dosage and shortening the interval of infusions provided effectiveness again. Infliximab would be a good choice for adolescent patients with TA refractory to conventional treatments. However, we should carefully monitor safety and efficacy of this agent considering its peculiarity.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Arteritis de Takayasu/tratamiento farmacológico , Adolescente , Anticuerpos Monoclonales/efectos adversos , Femenino , Humanos , InfliximabRESUMEN
Strategies effective for accelerating methotrexate removal in delayed methotrexate excretion have not been universally accepted. The authors report a case of a 12-year-old girl with osteosarcoma who developed acute renal failure immediately after the first administration of high-dose methotrexate. Plasma methotrexate was effectively removed with repeated charcoal hemoperfusion in addition to plasma exchange and leucovorin rescue. Charcoal hemoperfusion was most effective for reducing plasma methotrexate with approximately 50% of methotrexate being reduced during each of the procedures. No rebound increase in MTX levels was observed. The patient received further therapy with other cancer drugs and has been well for 3.5 years.
Asunto(s)
Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/terapia , Antimetabolitos Antineoplásicos/efectos adversos , Hemoperfusión , Metotrexato/efectos adversos , Antimetabolitos Antineoplásicos/administración & dosificación , Neoplasias Óseas/sangre , Neoplasias Óseas/tratamiento farmacológico , Carbón Orgánico , Niño , Femenino , Humanos , Metotrexato/administración & dosificación , Osteosarcoma/sangre , Osteosarcoma/tratamiento farmacológico , Radio (Anatomía)RESUMEN
The therapeutic efficacy of corticosteroids and immunosuppressants on secretary glands of children with Sjögren syndrome was investigated examining the lip-biopsy specimen on both lymphocyte infiltration and fibrosis. Six children with primary Sjögren syndrome and two children with lupus-associated secondary Sjögren syndrome were evaluated according to the intensity of therapy. The shorter the term of medications of corticosteroids and immunosuppressants were, the lesser the extents of lymphocyte infiltration and fibrosis were, and the lower the doses of medications were, the lesser the efficacy was. Thus, in childhood Sjögren syndrome, appropriate corticosteroids and immunosuppressants may provide the suppressive effects on the progressive inflammatory destruction of secretary glands. Further evaluation with more patients is needed to determine the inclusion criteria of these treatments for sicca syndrome, especially in cases with no other organ involvement.