Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 51
Filtrar
1.
Eur J Med Genet ; : 103767, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31536830

RESUMO

BACKGROUND: Glycogen storage disease type Ib (GSD-Ib) is an inherited metabolic disorder caused by autosomal recessive mutations in SLC37A4 coding for the glucose-6-phosphate transporter. Neutropenia represents major feature of GSD-Ib along with metabolic disturbances. Previous research in GSD-Ib patients did not reveal significant genotype-phenotype correlation. Our objective was to explore the frequency and severity of neutropenia and it's complications in relation to genotype of GSD-Ib patients. METHODS: We estimated cumulative incidence of neutropenia and severe neutropenia, relation of genotype to absolute neutrophil count (ANC), and dynamics of ANC during serious bacterial infections (SBI) in a cohort of Serbian GSD Ib patients. Impact of genotype on GSD Ib-related inflammatory bowel disease (IBD) was also assessed. RESULTS: Absolute neutrophil count (ANC) < 1500/mm3 was present in all 33 patients, with severe neutropenia (ANC<500/mm3) occurring in 60.6% of patients. The median age at neutropenia onset was 24 months, while severe neutropenia developed at median of 4.5 years. The ANC was elevated during 90.5% episodes of SBI. Genotypes c.81T>A/c.785G>A and c.81T>A/c.1042_1043delCT are associated with earlier onset of neutropenia. Patients carrying c.785G>A mutation express a higher capacity for ANC increase during SBI. Inflammatory bowel disease was diagnosed in 8 patients (24.2% of total) with median age of onset at 7 years. Risk for IBD occurrence was not significantly affected by gender, genotype and severity of neutropenia. CONCLUSIONS: We may conclude that certain mutations in SLC37A4 influence the risk for severe neutropenia occurrence but also affect the capacity to increase ANC during SBI.

2.
J Allergy Clin Immunol ; 141(1): 322-328.e10, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28392333

RESUMO

BACKGROUND: Rare DNA breakage repair disorders predispose to infection and lymphoreticular malignancies. Hematopoietic cell transplantation (HCT) is curative, but coadministered chemotherapy or radiotherapy is damaging because of systemic radiosensitivity. We collected HCT outcome data for Nijmegen breakage syndrome, DNA ligase IV deficiency, Cernunnos-XRCC4-like factor (Cernunnos-XLF) deficiency, and ataxia-telangiectasia (AT). METHODS: Data from 38 centers worldwide, including indication, donor, conditioning regimen, graft-versus-host disease, and outcome, were analyzed. Conditioning was classified as myeloablative conditioning (MAC) if it contained radiotherapy or alkylators and reduced-intensity conditioning (RIC) if no alkylators and/or 150 mg/m2 fludarabine or less and 40 mg/kg cyclophosphamide or less were used. RESULTS: Fifty-five new, 14 updated, and 18 previously published patients were analyzed. Median age at HCT was 48 months (range, 1.5-552 months). Twenty-nine patients underwent transplantation for infection, 21 had malignancy, 13 had bone marrow failure, 13 received pre-emptive transplantation, 5 had multiple indications, and 6 had no information. Twenty-two received MAC, 59 received RIC, and 4 were infused; information was unavailable for 2 patients. Seventy-three of 77 patients with DNA ligase IV deficiency, Cernunnos-XLF deficiency, or Nijmegen breakage syndrome received conditioning. Survival was 53 (69%) of 77 and was worse for those receiving MAC than for those receiving RIC (P = .006). Most deaths occurred early after transplantation, suggesting poor tolerance of conditioning. Survival in patients with AT was 25%. Forty-one (49%) of 83 patients experienced acute GvHD, which was less frequent in those receiving RIC compared with those receiving MAC (26/56 [46%] vs 12/21 [57%], P = .45). Median follow-up was 35 months (range, 2-168 months). No secondary malignancies were reported during 15 years of follow-up. Growth and developmental delay remained after HCT; immune-mediated complications resolved. CONCLUSION: RIC HCT resolves DNA repair disorder-associated immunodeficiency. Long-term follow-up is required for secondary malignancy surveillance. Routine HCT for AT is not recommended.


Assuntos
Quebras de DNA de Cadeia Dupla , Distúrbios no Reparo do DNA/genética , Distúrbios no Reparo do DNA/terapia , Reparo do DNA , Transplante de Células-Tronco Hematopoéticas , Adolescente , Alelos , Criança , Pré-Escolar , Distúrbios no Reparo do DNA/diagnóstico , Distúrbios no Reparo do DNA/mortalidade , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Mutação , Prognóstico , Resultado do Tratamento , Viroses , Adulto Jovem
3.
Turk J Pediatr ; 60(6): 735-738, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-31365212

RESUMO

Jevtic D, Djokic D, Redzic D, Aleksic D, Parezanovic M, Pasic S. Secondary hemophagocytic lymphohistiocytosis in a child with Leptospira infection: A case report. Turk J Pediatr 2018; 60: 735-738. Leptospirosis caused by spirochetes of the genus Leptospira in most patients result in very mild illness without jaundice. However, a small portion of patients develop various complications due to the involvement of multiple organ systems. Hemophagocytic lymphohistiocytosis is characterized by prolonged fever, hepatosplenomegaly and cytopenias, hyperferritinemia and hypertriglyceridemias, hyperfibrinogenemia, and hemophagocytosis in bone marrow, lymph nodes, spleen, or liver. Hemophagocytic lymphohistiocytosis associated with leptospirosis is a very rare condition and it should be considered in patients with multiple organ dysfunctions, together with adequate laboratory findings. It can delay the correct diagnosis of leptospirosis and contribute to an adverse outcome. We present a 13-year-old girl with secondary hemophagocytic lymphohistiocytosis caused by leptospira infection and favorable outcome with appropriate antibiotics and corticosteroid therapy.

4.
J Allergy Clin Immunol ; 139(4): 1282-1292, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27697500

RESUMO

BACKGROUND: X-linked hyper-IgM syndrome (XHIGM) is a primary immunodeficiency with high morbidity and mortality compared with those seen in healthy subjects. Hematopoietic cell transplantation (HCT) has been considered a curative therapy, but the procedure has inherent complications and might not be available for all patients. OBJECTIVES: We sought to collect data on the clinical presentation, treatment, and follow-up of a large sample of patients with XHIGM to (1) compare long-term overall survival and general well-being of patients treated with or without HCT along with clinical factors associated with mortality and (2) summarize clinical practice and risk factors in the subgroup of patients treated with HCT. METHODS: Physicians caring for patients with primary immunodeficiency diseases were identified through the Jeffrey Modell Foundation, United States Immunodeficiency Network, Latin American Society for Immunodeficiency, and Primary Immune Deficiency Treatment Consortium. Data were collected with a Research Electronic Data Capture Web application. Survival from time of diagnosis or transplantation was estimated by using the Kaplan-Meier method compared with log-rank tests and modeled by using proportional hazards regression. RESULTS: Twenty-eight clinical sites provided data on 189 patients given a diagnosis of XHIGM between 1964 and 2013; 176 had valid follow-up and vital status information. Sixty-seven (38%) patients received HCT. The average follow-up time was 8.5 ± 7.2 years (range, 0.1-36.2 years). No difference in overall survival was observed between patients treated with or without HCT (P = .671). However, risk associated with HCT decreased for diagnosis years 1987-1995; the hazard ratio was significantly less than 1 for diagnosis years 1995-1999. Liver disease was a significant predictor of overall survival (hazard ratio, 4.9; 95% confidence limits, 2.2-10.8; P < .001). Among survivors, those treated with HCT had higher median Karnofsky/Lansky scores than those treated without HCT (P < .001). Among patients receiving HCT, 27 (40%) had graft-versus-host disease, and most deaths occurred within 1 year of transplantation. CONCLUSION: No difference in survival was observed between patients treated with or without HCT across all diagnosis years (1964-2013). However, survivors treated with HCT experienced somewhat greater well-being, and hazards associated with HCT decreased, reaching levels of significantly less risk in the late 1990s. Among patients treated with HCT, treatment at an early age is associated with improved survival. Optimism remains guarded as additional evidence accumulates.


Assuntos
Transplante de Células-Tronco Hematopoéticas/mortalidade , Síndrome de Imunodeficiência com Hiper-IgM/mortalidade , Síndrome de Imunodeficiência com Hiper-IgM/terapia , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Seguimentos , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Tempo , Adulto Jovem
5.
J Clin Immunol ; 35(6): 538-49, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26271390

RESUMO

PURPOSE: Nijmegen Breakage Syndrome (NBS) is a rare inherited condition, characterized by microcephaly, chromosomal instability, immunodeficiency, and predisposition to malignancy. This retrospective study, characterizing the clinical and immunological status of patients with NBS at time of diagnosis, was designed to assess whether any parameters were useful in disease prognosis, and could help determine patients qualified for hematopoietic stem cell transplantation. METHODS: The clinical and immunological characteristics of 149 NBS patients registered in the online database of the European Society for Immune Deficiencies were analyzed. RESULTS: Of the 149 NBS patients, 91 (61%), of median age 14.3 years, remained alive at the time of analysis. These patients were clinically heterogeneous, with variable immune defects, ranging from negligible to severe dysfunction. Humoral deficiencies predisposed NBS patients to recurrent/chronic respiratory tract infections and worsened long-term clinical prognosis. Eighty malignancies, most of lymphoid origin (especially non-Hodgkin's lymphomas), were diagnosed in 42% of patients, with malignancy being the leading cause of death in this cohort. Survival probabilities at 5, 10, 20 and 30 years of age were 95, 85, 50 and 35%, respectively, and were significantly lower in patients with than without malignancies. CONCLUSIONS: The extremely high incidence of malignancies, mostly non-Hodgkin's lymphomas, was the main risk factor affecting survival probability in NBS patients. Because treatment of NBS is very difficult and frequently unsuccessful, the search for an alternative medical intervention such as hematopoietic stem cell transplantation is of great clinical importance.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndrome de Quebra de Nijmegen/diagnóstico , Fatores de Tempo , Adolescente , Adulto , Criança , Pré-Escolar , Instabilidade Cromossômica , Feminino , Humanos , Síndromes de Imunodeficiência , Lactente , Linfoma não Hodgkin , Masculino , Microcefalia , Síndrome de Quebra de Nijmegen/genética , Síndrome de Quebra de Nijmegen/terapia , Prognóstico , Estudos Retrospectivos , Adulto Jovem
7.
Am J Infect Control ; 42(9): 942-56, 2014 09.
Artigo em Inglês | MEDLINE | ID: mdl-25179325

RESUMO

We report the results of an International Nosocomial Infection Control Consortium (INICC) surveillance study from January 2007-December 2012 in 503 intensive care units (ICUs) in Latin America, Asia, Africa, and Europe. During the 6-year study using the Centers for Disease Control and Prevention's (CDC) U.S. National Healthcare Safety Network (NHSN) definitions for device-associated health care-associated infection (DA-HAI), we collected prospective data from 605,310 patients hospitalized in the INICC's ICUs for an aggregate of 3,338,396 days. Although device utilization in the INICC's ICUs was similar to that reported from ICUs in the U.S. in the CDC's NHSN, rates of device-associated nosocomial infection were higher in the ICUs of the INICC hospitals: the pooled rate of central line-associated bloodstream infection in the INICC's ICUs, 4.9 per 1,000 central line days, is nearly 5-fold higher than the 0.9 per 1,000 central line days reported from comparable U.S. ICUs. The overall rate of ventilator-associated pneumonia was also higher (16.8 vs 1.1 per 1,000 ventilator days) as was the rate of catheter-associated urinary tract infection (5.5 vs 1.3 per 1,000 catheter days). Frequencies of resistance of Pseudomonas isolates to amikacin (42.8% vs 10%) and imipenem (42.4% vs 26.1%) and Klebsiella pneumoniae isolates to ceftazidime (71.2% vs 28.8%) and imipenem (19.6% vs 12.8%) were also higher in the INICC's ICUs compared with the ICUs of the CDC's NHSN.


Assuntos
Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Controle de Infecções/estatística & dados numéricos , África/epidemiologia , Ásia/epidemiologia , Europa (Continente)/epidemiologia , Humanos , Controle de Infecções/métodos , Unidades de Terapia Intensiva , América Latina/epidemiologia , Estudos Prospectivos , Estados Unidos/epidemiologia
8.
Pancreatology ; 14(5): 330-4, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25163808

RESUMO

BACKGROUND: Current predictive severity scores for pediatric acute pancreatitis are either extrapolated from adult studies or difficult to use in practice. The aim of this study was to assess the value of the plasma D-dimer level as a marker of severity and outcome in pediatric AP. METHODS: 36 patients (aged 1-17 yrs) with AP were included in the study. Levels of D-dimer and other routine laboratory parameters for AP were determined on admission. The Pediatric Acute Pancreatitis Severity Score was used to assess disease severity. The development of systemic and local complications was also recorded. RESULTS: D-dimer level was significantly higher in a group of patients with complications, median 1189.5 (271-4800) vs 172.5 (105-1086) in a group of patients without complications (p < 0.001). D-dimer showed high precision in the prediction of acute necrotic collection, with the optimal cut-off values of 442.5 µg/L, Sensitivity (Sn) 100%, Specificity (Sp) 62.1% and in the prediction of multiple organ failure with optimal cut-off value 1189 µg/L, Sn 100% and Sp 87.5%. According to the areas under the curve (AUCs) of each parameter, D-dimer seemed to have predictive power similar to PAPS score and higher than C-reactive protein and Lactate dehydrogenase level. CONCLUSION: D-dimer level may be a simple clinical predictor of severity in pediatric acute pancreatitis.


Assuntos
Técnicas de Apoio para a Decisão , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Pancreatite/diagnóstico , Índice de Gravidade de Doença , Doença Aguda , Adolescente , Área Sob a Curva , Biomarcadores/sangue , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Insuficiência de Múltiplos Órgãos/etiologia , Pancreatite/sangue , Pancreatite/complicações , Pancreatite Necrosante Aguda/sangue , Pancreatite Necrosante Aguda/complicações , Pancreatite Necrosante Aguda/diagnóstico , Prognóstico , Estudos Retrospectivos , Sensibilidade e Especificidade
9.
Patient Prefer Adherence ; 8: 323-30, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24669189

RESUMO

INTRODUCTION: The aims of this study were to evaluate levels of health-related quality of life (HRQOL) and the presence of anxiety and depressive symptoms in children with primary immunodeficiency disease (PID) in Serbia. MATERIALS AND METHODS: Self- and parent-rated data from 25 children with PID were available. As controls, data from 50 children with juvenile idiopathic arthritis (JIA) and 89 healthy children were included. The Pediatric Quality of Life Inventory was used for HRQOL assessments. Anxiety symptoms were identified using the Screen for Child Anxiety-Related Emotional Disorders questionnaire, while depressive symptoms were identified using the Mood and Feeling Questionnaire. RESULTS: Children with PID had significantly lower Pediatric Quality of Life Inventory total scores compared to children with JIA and healthy children as child-rated (P=0.02) and parent-rated (P<0.001). Specifically, they had significantly lowered emotional functioning compared to children with JIA, and social functioning compared to both children with JIA and healthy children. School functioning was significantly lower among children with PID (parent-rated only). By parent-rated responses, six (24%) out of 25 children with PID had significant anxiety symptoms, while five (20%) children had significant depressive symptoms, which was statistically higher than among children with JIA and healthy controls (P=0.05). CONCLUSION: HRQOL could be significantly compromised in children with PID, particularly across such psychosocial domains as emotional, social, and school. These children were also found to be at an increased risk for suffering significant anxiety and depressive symptoms.

10.
J Clin Immunol ; 34(3): 304-8, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24481607

RESUMO

Severe combined immunodeficiency (SCID), including the 'variant' Omenn syndrome (OS), represent a heterogeneous group of monogenic disorders characterized by defect in differentiation of T- and/or B lymphocytes and susceptibility to infections since birth. In the period of 25 years, between January 1986 and December 2010, a total of 21 patients (15 SCID, 6 OS) were diagnosed in Mother & Child Health Institute of Serbia, a tertiary-care teaching University hospital and a national referral center for patients affected with primary immunodeficiency (PID). The diagnoses were based on anamnestic data, clinical findings, and immunological and genetic analysis. The median age at the onset of the first infection was the 2nd month of life. Seven (33 %) patients had positive family history for SCID. Out of five male infants with T-B+NK- SCID phenotype, mutation analysis revealed interleukin-2 (common) gamma-chain receptor (IL2RG) mutations in 3 with positive X-linked family history, and Janus-kinase (JAK)-3 gene defects in the other two. Six patients had T-B-NK+ SCID phenotype and further 6 features of OS, 11 of which had recombinase-activating gene (RAG1or RAG2) and 1 Artemis gene mutations. One child with T+B+NK+ SCID phenotype as well had proven RAG mutation. One child each with T-B+NK+ SCID phenotype, CD8 lymphopenia and unknown phenotype remained without known underlying genetic defect. Of the eight patients who underwent hematopoetic stem cell transplant (HSCT) 5 survived, the other 13 died between 2 days and 12 months after diagnosis was made. Early diagnosis of SCID, before onset of severe infections, offers possibility for HSCT and cure. Education of primary-care pediatricians, in particular including awareness of the risk of using live vaccines and non-irradiated blood products, should improve prognosis of SCID in our setting.


Assuntos
Imunodeficiência Combinada Severa/epidemiologia , Idade de Início , Diagnóstico Tardio , Transplante de Células-Tronco Hematopoéticas , Humanos , Lactente , Recém-Nascido , Montenegro/epidemiologia , Triagem Neonatal , Diagnóstico Pré-Natal , Estudos Retrospectivos , Sérvia/epidemiologia , Imunodeficiência Combinada Severa/diagnóstico , Imunodeficiência Combinada Severa/terapia , Resultado do Tratamento
11.
Pediatr Neurol ; 50(3): 233-7, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24332871

RESUMO

BACKGROUND: Hemophagocytic lymphohistiocytosis is a rare multisystem disorder characterized by proliferation and diffuse infiltration multiple organs with histiocytes, including the central nervous system. PATIENTS AND METHODS: Thirty children diagnosed with hemophagocytic lymphohistiocytosis between 1997 and 2010 were reviewed and analyzed. Central nervous system disease involvement was defined as the presence of neurological symptoms and signs or elevated values of cerebrospinal fluid cells and/or proteins. RESULTS: Among the 30 patients, 17 (56%) had central nervous system involvement. Fourteen patients (46%) presented with neurological symptoms including seizures, irritability, bulging fontanelle, cranial nerve palsy, or disturbance of consciousness, whereas the remaining three patients developed central nervous system symptoms during the course of the disease. Seventeen patients (56%) had cerebrospinal fluid abnormalities. Neuroradiological studies were performed in nine patients. The most common findings were edema, atrophy, subcortical necrosis, and high signal intensity on T2-weighted magnetic resonance imaging. All patients were treated according to the Hemophagocytic Lymphohistiocytosis-94 and Hemophagocytic Lymphohistiocytosis-2004 protocols. Patients with central nervous system involvement had greater mortality. In prediction of the outcome, the cutoff value for cerebrospinal fluid protein was 470 mg/L. The most common neurological sequela was psychomotor delay. CONCLUSION: Central nervous system involvement in hemophagocytic lymphohistiocytosis is common and is associated with poor outcome.


Assuntos
Encéfalo/patologia , Encéfalo/fisiopatologia , Linfo-Histiocitose Hemofagocítica/patologia , Linfo-Histiocitose Hemofagocítica/fisiopatologia , Adolescente , Pré-Escolar , Feminino , Humanos , Lactente , Linfo-Histiocitose Hemofagocítica/líquido cefalorraquidiano , Linfo-Histiocitose Hemofagocítica/diagnóstico , Imagem por Ressonância Magnética , Masculino , Prognóstico , Curva ROC , Análise de Sobrevida , Tomografia Computadorizada por Raios X
13.
Ital J Pediatr ; 39: 59, 2013 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-24044622

RESUMO

We report on pediatric patient with Nijmegen breakage syndrome (NBS), a rare DNA repair disorder characterized by microcephaly, immunodeficiency and predisposition to malignant lymphomas, who developed juvenile idiopathic arthritis (JIA)-like polyarthritis. In patients with primary immunodeficiencies (PID), septic arthritis due to pyogenic bacteria or mycoplasmal arthritis are the most common osteoarticular manifestations. In certain PID, chronic, non-infectious arthritis resembling rheumatoid arthritis may occur. In our patient microbiologic cultures of synovial fluid including Mycoplasma spp. were negative. At first, because of suspected mycoplasmal arthritis we used macrolides and doxycycline combined with hydroxychloroquine but without therapeutic response. However, the use of rituximab led to remission of her polyarthritis lasting for 9 months. Autoimmune features were rarely reported in NBS. An occurrence of JIA-like, chronic polyarthritis in NBS, a DNA repair disorder characterized by decreased tolerance of immunosuppressive drugs such as methotrexate and a high natural risk for lymphomas, makes therapeutic approach even more complex.


Assuntos
Artrite/tratamento farmacológico , Artrite/etiologia , Síndrome de Quebra de Nijmegen/complicações , Anti-Inflamatórios não Esteroides/uso terapêutico , Anticorpos Monoclonais Murinos/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite/diagnóstico por imagem , Artrite/genética , Criança , Doença Crônica , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Síndrome de Quebra de Nijmegen/genética , Síndrome de Quebra de Nijmegen/fisiopatologia , Radiografia , Doenças Raras , Medição de Risco , Rituximab , Índice de Gravidade de Doença , Resultado do Tratamento
14.
J Clin Microbiol ; 51(8): 2686-90, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23761151

RESUMO

In immunocompromized patients, including hematopoietic stem cell transplant (HSCT) recipients, life-threatening toxoplasmosis may result from reactivation of previous infection. We report a case of severe disseminated toxoplasmosis that developed early after allogeneic HSCT for T-cell lymphoblastic leukemia/lymphoma in a 15-year-old Toxoplasma gondii-seropositive boy with Nijmegen breakage syndrome, a rare genetic DNA repair disorder associated with immunodeficiency. The donor was the patient's HLA-identical brother. Prophylaxis with cotrimoxazole was discontinued a day before the HSCT procedure. Signs of lung infection appeared as early as day 14 post-HSCT. The presence of tachyzoite-like structures on Giemsa-stained bronchoalveolar lavage (BAL) fluid smears suggested toxoplasmosis. Real-time PCR targeted at the T. gondii AF146527 gene revealed extremely high parasite burdens in both blood and BAL fluid. Although immediate introduction of specific treatment resulted in a marked reduction of the parasite load and transient clinical improvement, the patient deteriorated and died of multiple organ failure on day 39 post-HSCT. Direct genotyping of T. gondii DNA from blood and BAL fluid with the PCR-restriction fragment length polymorphism method revealed type II alleles with SAG1, SAG2, and GRA6 markers but alleles of both type I and type II with GRA7. Additional analysis with 15 microsatellite markers showed that the T. gondii DNA was atypical and genetically divergent from that of the clonal type I, II, and III strains. This is the first report of increased clinical severity of toxoplasmosis associated with an atypical strain in the setting of immunosuppression, which emphasizes the need to diagnose and monitor toxoplasmosis by quantitative molecular methods in cases of reactivation risk.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hospedeiro Imunocomprometido , Toxoplasma/isolamento & purificação , Toxoplasmose/diagnóstico , Adolescente , Líquido da Lavagem Broncoalveolar/parasitologia , Evolução Fatal , Genótipo , Humanos , Masculino , Pneumonia/parasitologia , Pneumonia/patologia , Proteínas de Protozoários/genética , Reação em Cadeia da Polimerase em Tempo Real , Toxoplasma/classificação , Toxoplasma/genética
16.
Ann Rheum Dis ; 72(9): 1503-9, 2013 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-23100607

RESUMO

OBJECTIVES: To evaluate therapeutic approaches and response to therapy in juvenile systemic lupus erythematosus (SLE) with renal involvement in a large prospective international cohort from four geographic areas. METHODS: New onset and flared patients with active renal disease (proteinuria ≥0.5 g/24 h) were enrolled in 2001-2004. Therapeutic approaches and disease activity parameters were analysed at baseline, 6, 12 and 24 months. Response was assessed by the PRINTO/ACR criteria. RESULTS: 218/557 (79.8% female subjects, 117 new onset and 101 flared) patients with active renal disease were identified; 66 patients were lost to follow-up and 11 died. Mean age at disease onset for new onset group was higher than for flared group (13.1 vs 10.2 years, p<0.0001). At baseline, both groups had similar renal activity with similar median doses of corticosteroids (1.0-0.76 mg/kg/day). Cyclophosphamide (43.1%) and azathioprine (22%) were the most common immunosuppressive drugs. At baseline, South American patients received higher doses of corticosteroids than in other areas in new onset (median 1.16 vs 0.8-1 mg/kg/day) while cyclophosphamide use was similar in all four regions in the new onset group. There were no differences regarding the use of azathioprine or mycophenolate mofetil worldwide. PRINTO 70 response was reached in a greater percentage of new onset versus flared patients (74.8% vs 53.3%; p=0.005) at 6 months while at 24 months ACR 90 was reached by 69.9% and 56.1%, respectively. CONCLUSIONS: New onset and flared juvenile SLE improved similarly over 24 months with minimal differences in therapeutic approaches worldwide.


Assuntos
Azatioprina/uso terapêutico , Ciclofosfamida/uso terapêutico , Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Adolescente , Idade de Início , Estudos de Coortes , Quimioterapia Combinada , Feminino , Nível de Saúde , Humanos , Cooperação Internacional , Nefrite Lúpica/epidemiologia , Nefrite Lúpica/patologia , Nefrite Lúpica/urina , Masculino , Estudos Prospectivos , Proteinúria/patologia , Recidiva , Índice de Gravidade de Doença , Resultado do Tratamento
17.
J Pediatr Hematol Oncol ; 34(6): 453-6, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22735880

RESUMO

BACKGROUND: An association between hemophagocytic lymphohistiocytosis (HLH) and severe transient left ventricular (LV) hypertrophy has not been described to date. Possible explanations, including etoposide toxicity, are discussed. OBSERVATION: A 2-month-old male infant with HLH was treated according to the HLH-2004 protocol. Initial cardiac evaluation was within normal limits. During the second month of therapy, a heart murmur was discovered; electrocardiogram demonstrated signs of LV hypertrophy, and echocardiogram confirmed the presence of thickness of LV walls. This complication was transient: clinical findings, echocardiogram, and electrocardiogram recorded 6 months afterward were all within normal limits. CONCLUSIONS: The case suggests the need for close echocardiographic monitoring during HLH treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Hipertrofia Ventricular Esquerda/induzido quimicamente , Hipertrofia Ventricular Esquerda/prevenção & controle , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Ciclosporina/administração & dosagem , Dexametasona/administração & dosagem , Ecocardiografia , Eletrocardiografia , Etoposídeo/administração & dosagem , Humanos , Lactente , Masculino , Prognóstico
18.
Clin Exp Rheumatol ; 30(1 Suppl 70): S162-8, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22640658

RESUMO

OBJECTIVES: To evaluate the performance of the Birmingham Vasculitis Activity Score (BVAS) v3 and the Disease Extent Index (DEI) for the assessment of disease activity in 4 primary childhood (c-) systemic vasculitides. METHODS: Patients fulfilling the EULAR/PRINTO/PRES (Ankara) c-vasculitis classification criteria for Henoch-Schönlein purpura (HSP), childhood (c) polyarteritis nodosa (c-PAN), c-Wegener's granulomatosis (c-WG) and c-Takayasu arteritis (c-TA) with disease duration at the time of diagnosis ≤3 months were extracted from the PRINTO database. The performance of the BVAS and DEI were examined by assessing convergent validity, the pattern of disease involvement, and responsiveness. We also evaluated alternative unweighted scoring methods for both tools. RESULTS: The analysis set included 796 patients with 669 HSP, 80 c-PAN, 25 c-WG and 22 c-TA. The median age at diagnosis was 6.9 years (6.6-12) and median delay in making the diagnosis from the onset of signs/symptoms was 0.01 (0.003-0.027) years. A strong correlation was found between the BVAS and DEI (rs=0.78) while correlation with the physician global assessment was moderate (rs=0.48) with BVAS and poor with DEI (rs=0.25). Both the BVAS and DEI sub-scores and total scores were able to descrive the disease involvement in the 4 childhood vasculitides. Responsiveness was large (>1.5) for both tools. The performance characteristics of the BVAS and DEI with the unweighted methods were comparable. CONCLUSIONS: This study demonstrates that both the BVAS and DEI are valid tools for the assessment of the level of disease activity in a large cohort of childhood acute and chronic vasculitides.


Assuntos
Indicadores Básicos de Saúde , Vasculite/diagnóstico , Criança , Diagnóstico Diferencial , Granulomatose com Poliangiite/diagnóstico , Humanos , Poliarterite Nodosa/diagnóstico , Valor Preditivo dos Testes , Prognóstico , Púrpura de Schoenlein-Henoch/diagnóstico , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Arterite de Takayasu/diagnóstico , Terminologia como Assunto , Vasculite/classificação
19.
J Pediatr Hematol Oncol ; 34(6): 467-71, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22258354

RESUMO

We report a 2.5-year-old boy with an X-linked lymphoproliferative disease (XLP) phenotype who presented with human herpes virus-8 (HHV-8)-related hemophagocytic lymphohistiocytosis (HLH). XLP is a rare primary immunodeficiency characterized by extreme susceptibility to herpes viruses, mainly Epstein-Barr virus (EBV). Approximately 60% of patients with XLP present with fulminant mononucleosis associated with HLH, whereas remaining patients present with hypogammaglobulinemia or lymphoproliferative disease. Most commonly, one of the XLP phenotypes appears after exposure to EBV, but at least 12% of affected individuals developed symptoms without an evidence of EBV infection. Rarely, patients with XLP may present with central nervous system vasculitis or aplastic anemia. HHV-8 is lymphotrophic and it is associated with lymphoproliferative disorders and Kaposi sarcoma in immunodeficient hosts. Kaposi sarcoma rarely occurs in children with well-defined primary immunodeficiency. Also, HHV-8-related HLH was previously reported in 2 siblings with a perforin gene deficiency. Recently, it became evident that besides EBV, other viruses may trigger the symptoms in XLP. We report for the first time HHV-8-related HLH in EBV-negative pediatric patient with an XLP phenotype.


Assuntos
Infecções por Herpesviridae/complicações , Herpesvirus Humano 8/patogenicidade , Linfo-Histiocitose Hemofagocítica/etiologia , Transtornos Linfoproliferativos/etiologia , Pré-Escolar , Infecções por Herpesviridae/virologia , Herpesvirus Humano 8/isolamento & purificação , Humanos , Linfo-Histiocitose Hemofagocítica/diagnóstico , Transtornos Linfoproliferativos/diagnóstico , Masculino , Fenótipo , Prognóstico
20.
Arthritis Rheum ; 63(5): 1452-8, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21538322

RESUMO

OBJECTIVE: The current treatment options for systemic-onset juvenile idiopathic arthritis (JIA) are methotrexate, steroids, and biologic agents. This study was undertaken to evaluate the safety of the orally active histone deacetylase inhibitor givinostat (ITF2357) and its ability to affect the disease. METHODS: Givinostat was administered orally, for up to 12 weeks at a dosage of 1.5 mg/kg/day, to 17 patients with systemic-onset JIA who had had active disease for ≥1 month. Disease activity was clinically assessed using the American College of Rheumatology Pediatric 30 (ACR Pedi 30), ACR Pedi 50, or ACR Pedi 70 criteria for improvement and a systemic feature score. The primary goal was safety and the primary efficacy end point was the number of patients completing 12 weeks of treatment who were responders. RESULTS: Givinostat was safe and well tolerated, with adverse events (AEs) being mild or moderate, of short duration, and self-limited. The 17 patients from the intent-to-treat population reported a total of 44 AEs, and the 9 patients in the per-protocol population reported a total of 25. Six AEs in 3 patients (nausea, vomiting, and fatigue) were related to the study drug, but each resolved spontaneously and no patient was withdrawn from the study due to drug-related AEs. In the per-protocol population at week 4, the improvement as measured by the ACR Pedi 30, ACR Pedi 50, and ACR Pedi 70, respectively, was 77.8%, 55.6%, and 22.2%, and this increased further to 77.8%, 77.8%, and 66.7% at week 12. The most consistent finding was the reduction in the number of joints with active disease or with limited range of motion. CONCLUSION: After 12 weeks, givinostat exhibited significant therapeutic benefit in patients with systemic-onset JIA, particularly with regard to the arthritic component of the disease, and showed an excellent safety profile.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Inibidores de Histona Desacetilases/uso terapêutico , Ácidos Hidroxâmicos/uso terapêutico , Adolescente , Antirreumáticos/administração & dosagem , Criança , Feminino , Inibidores de Histona Desacetilases/efeitos adversos , Humanos , Ácidos Hidroxâmicos/efeitos adversos , Análise de Intenção de Tratamento , Masculino , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA