Corticosteroid-induced osteoporosis in children: outcome after two-year follow-up, risk factors, densitometric predictive cut-off values for vertebral fractures.

OBJECTIVE: To identify factors that contribute to a decreased Z score of volumetric spine bone mineral density (ZvSBMD) and the development of vertebral fractures (VF) in children receiving chronic systemic corticosteroid therapy (SCT); to describe their outcome after 2 years, and to define predictive threshold values for ZvSBMD for VF. METHODS: Fifty-five children on SCT for >or= 6 months were prospectively followed for 2 years. In children with a ZvSBMD > -1.5, we prescribed preventive measures for osteoporosis and densitometry annually. In children with ZvSBMD

Changes in the survival of patients with systemic lupus erythematosus in childhood: 30 years experience in Chile.

The objective of this study was to analyse the survival rate and cause of death in children with systemic lupus erythematosus (SLE) during the past 30 years in Chile. A retrospective analysis was performed between 1969 and 2000 on patients attending pediatric rheumatology centres in Santiago, Chile. Survival and causes of death in 31 children followed from 1969 to 1980 fulfilling the 1982 American College of Rheumatology criteria for SLE and treated with oral steroids were compared with 50 other patients who were treated with oral steroids and an aggressive treatment of IV bolus of cyclophosphamide (38 patients) and azathioprine (12 patients). Global survival at five and 10 years follow-up for the patients studied from 1969 to 1980 was 68 and 40%, respectively. During the second study period these values were significantly improved and global survival reached 95% at five years and 90% at 10 years follow-up (P < 0.05). Survival at 10 years follow-up for patients with lupus nephropathy increased from 28% (study period 1964-1980) to 86% (study period 1984-2000). Twelve children died (38%) during the 1964-1980 study period. The causes of death were six due to kidney failure, three due to infectious conditions and another three of unknown causes. During the 1980-2000 study period mortality reached 6% (three cases), two cases died of a lupus flare-up and one case due to infection. In the last three decades, we have seen an important increase in the survival of children with SLE, especially in those patients with renal involvement. Management with immunosuppressive drugs, such as IV cyclophosphamide or azathioprine has changed the prognosis in these children. These results demonstrate that our children with SLE increased their life expectancy but are now faced with new types of morbidity because of the sequelae related to the disease itself.

Características clínicas e inmunológicas de veinte pacientes con síndrome de DiGeorge / Clinical and inmunological characteristics of twenty patients with DiGeorge syndrome

El síndrome de DiGeorge presenta alteraciones en estructuras faciales, cardiacas conotruncales, paratiroides, timo y vía aérea, con amplio rango de deficiencia en linfocitos T. Objetivos. Describir las manifestaciones clínicas, la frecuencia y tipo de malformaciones de vía aérea asociadas y los recuentos de linfocitos CD3, CD4 Y CD8. Pacientes y métodos. Estudio multicéntrico retrospectivo de 20 pacientes con diagnóstico de Síndrome de DiGeorge provenientes de 5 hospitales de Santiago de Chile, entre 1995 y 2004. Resultados. En todos los pacientes se realizó diagnóstico en periodo neonatal, por la presencia de cardipatía e hipocalcemia. Las cardiopatías más frecuentes fueron la tetralogía de Fallot e interrupción de arco aórtico tipo B. La malformación de via aérea más frecuente fue la laringomalacia. Se demostró deleción de la región 22q 11.2 en 88% de los pacientes y 62,5% presentó infeccones recurrentes. Las subpoblaciones de dinfocitos CD3, CD4 y CD8 se mantuvieron en rangos normales en la mayoría de los pacientes pero tres enfermos con recuentos de linfocitos CD4<400/mm3 fallecieron durante el seguimiento. Conclusión. Se encontró amplia variabilidad clínica, alta frecuencia de malformaciones asociadas de la vía aérea como de infecciones recurrentes. Recuentos de linfocitos CD4<400/mm3 se encontró en todos los pacientes fallecidos (AU)

DiGeorge síndrome presents dysmorphic facial structures, conotruncal cardiac defects, parathyroid,thymus, airway malformations and a broad range of T-cell deficiency. Objetives. To describe the coinical findings, frecuency and type of airwqy malfromations and CD3,CD4 and CD8 T-cells counts. Patients and methods. A multicentric, retrospective chart review of twenty patients with diagnosis of DiGeorge sysdrome from five hospitals fo Santiago, Chile, between 1995 and 2004. Results. All the patients gad neonatal diagnosis with hypocalcemia and congenital heart desease. The most frequent conotruncal cardiac defects were tetralogy of Fallot and interrumpted aortic arch tipe B. Laryngornalacia was the most frequent airway malformation. We found 22q 11.2 deletion in 88% of the patients and 62,5% had recurrent infections. The CD3, CD4 and CD8 T-cell counts <400/mm3 were found in all the patients that died (AU)

[Clinical heterogeneity of the chromosome 22q11 microdeletion syndrome]. / Heterogeneidad de la presentación clínica del síndrome de microdeleción del cromosoma 22, región q11.

BACKGROUND: DiGeorge anomaly, velocardiofacial syndrome and conotruncal anomaly face syndrome are part of a group of congenital malformations of the chromosome 22q11 microdeletion syndrome, since they share certain phenotypic features as well as a common genetic abnormality. The malformations include mild facial dysmorphic features, conotruncal heart defects, thymic and parathyroid hypoplasia or aplasia and cleft palate. AIM: To describe the initial clinical presentation of children with clinical and molecular diagnosis of 22q11 microdeletion. PATIENTS AND METHODS: Ten children (seven male) with the phenotypic features of 22q11 microdeletion syndrome are reported. Microdeletion was detected in peripheral lymphocytes by fluorescent in situ hybridisation (FISH) with the TUPLE-1 DNA probe. RESULTS: Two children had abnormal karyotypes, one of them had a visible deletion and another child had an unbalanced translocation inherited from his mother who had a balanced translocation between chromosomes 14 and 22. Two of the 10 patients had an anterior laryngeal web, a malformation infrequently described in this syndrome. Five patients had the diagnosis of DiGeorge anomaly, had a more serious clinical presentation and a higher early mortality. CONCLUSIONS: The high frequency of the 22q11 microdeletion syndrome, estimated at 1:5.000 newborns, and its variable presentations requires a high level of awareness for its early diagnosis and appropriate management of associated complications.

[Crescentic glomerulonephritis with anti neutrophil cytoplasmic antibody in children. Cases report]. / Glomerulonefritis crescéntica con anticuerpos anticitoplasma de neutrofilos (+) en niños. Casos clínicos.

Anti neutrophil cytoplasmic antibodies are associated to vasculitis and crescentic glomerulonephritis in adults. However, this association has been seldom reported in children. We report two girls aged 12 and 15 years old with ANCA + glomerulonephritis. Both were subjected to a percutaneous kidney biopsy. One girl had to enter a chronic hemodialysis program. The other patient recovered her renal function and after 12 months of treatment with steroids and cyclophosphamide microscopic hematuria and proteinuria persist but with normal kidney function. ANCA should be measured in children with vasculitis and glomerulonephritis.

Time course of antibody response to tetanus toxoid and pneumococcal capsular polysaccharides in patients infected with HIV.

The temporal course of the humoral immune response to T-cell-dependent and T-cell-independent type 2 antigens was evaluated in HIV-infected patients. In all, 26 seropositive patients were vaccinated with tetanus toxoid and 23-valent pneumococcal vaccines; total IgG and IgG1 antibodies to tetanus toxoid (Ttox) and total IgG and IgG2 antibodies against 23 Streptococcus pneumoniae capsular antigens (PPS) were measured at baseline, 2 months, and 12 months after vaccination. For the Ttox, baseline levels of IgG1 (Ttox-IgG1) increased from 11.0 to 19.5 mg/L at 2 months postimmunization. Overall only 6 patients (23%) showed a significant response. At 12 months postvaccination, Ttox-IgG and T-tox-IgG1 were significantly lower than baseline levels (Ttox IgG basal; 11.0 mg/L, 12 months; 0.8 mg/L, Ttox IgG1 baseline; 13.1 mg/L, Ttox IgG1 12 months; 2.4 mg/L) and in 10 patients, antibodies that fell below protective levels (0.6 mg/L). In contrast with PPS, a significant response was observed at 2 and 12 months (PPS-IgG basal; 35.9 U/ml, 2 months; 151.4 U/ml, 12 months; 59.7 U/ml; PPS-IgG2 baseline 20.3 U/ml, 2 months; 113.2 U/ml, 12 months; 51.9 U/ml). Overall, 19 patients (76%) showed an immune response to pneumococcal polysaccharides antigens. Immunization with the Ttox T-cell-dependent antigen fails to elicit a significant immune response and may induce inhibition of antibody production in HIV-infected patients. In contrast, immunization with a T-cell-independent type 2 antigen can cause the pneumococcal polysaccharides to induce significant immune response in a high proportion of HIV-infected patients.

PIP: The temporal course of the humoral response to T-cell-dependent and T-cell-independent type 2 antigens was evaluated in HIV-infected patients. 26 HIV-seropositive patients were vaccinated with tetanus toxoid and 23-valent pneumococcal vaccines; total IgG and IgG1 antibodies to tetanus toxoid (Ttox) and total IgG and IgG2 antibodies against 23 Streptococcus pneumoniae capsular antigens (PPS) were measured at baseline, 2 months, and 12 months after vaccination. For the Ttox, baseline levels of IgG1 (Ttox-IgG1) increased from 11.0 to 19.5 mg/L at 2 months postimmunization. Overall, 6 patients (23%) showed a significant response. At 12 months postvaccination, Ttox-IgG and Ttox-IgG1 were significantly lower than baseline levels, and in 10 patients, antibodies fell below protective levels. In contrast with PPS, a significant response was observed at 2 and 12 months. Overall, 19 patients (76%) showed an immune response to pneumococcal polysaccharide antigens. Immunization with the Ttox T-cell-dependent antigen elicits no significant immune response and may induce inhibition of antibody production in HIV-infected patients. In contrast, immunization with a T-cell-independent type 2 antigen can cause the pneumococcal polysaccharides to induce significant immune response in a high proportion of HIV-infected patients.

[Functioning and non-functioning parathyroid cysts: entities with different origin and clinical characteristics in 2 cases]. / Quistes paratiroideos funcionantes y no funcionantes: entidades con origen y clínica diferente en dos casos.

We report two women presenting with parathyroid cysts. A 20 years old woman presented with goiter and a cystic lesion in the left thyroid lobe was identified on ultrasound examination and CAT scan. The patient had hypercalcemia and elevated PTH levels. The content of the cyst, obtained by needle aspiration, had an extremely high PTH concentration. The patient was operated, removing the cyst and a remaining thymus. Pathological study confirmed the diagnosis of a parathyroid cyst. An 11 years old girl presented with a mass in the left thyroid lobe. An ultrasound examination disclosed the presence of a cystic nodule. The patient was otherwise asymptomatic and laboratory work up was normal. The patient was operated and pathological examination of the surgical piece revealed a parathyroid cyst.

[Juvenile systemic rheumatoid arthritis and adult-onset Still's disease: comparison of clinical course]. / Artritis reumatoídea juvenil sistémica y enfermedad de Still del adulto: comparación de la evolución clínica.

The course of systemic juvenile rheumatoid arthritis (JRA) and that of Still's disease in the adult is unpredictable. The clinical course of 14 patients with JRA and 7 adults with Still's disease 6 months after onset was classified into 4 forms according to the persistence of joint manifestations after the cessation of systemic signs. a) monocyclic systemic form (5 children and 2 adults); b) polycyclic systemic form (3 children and 1 adult); c) monocyclic chronic joint form (3 children and 2 adults) and d) polycyclic chronic joint form (3 children, 2 adults). Seven of the 21 patients (5 children and 2 adults) developed joint sequelae, 5 with the polycyclic chronic joint form and 2 with the monocyclic chronic joint form. None of the patients with systemic forms, mono or polycyclic, developed sequelae. Thus, the course of patients with JRA and Still's disease may be used to predict development of joint sequelae.

[Di George syndrome]. / Síndrome de Di George.

Two patients with Di George syndrome are presented. Diagnosis was done at ages 4 months and 16 days respectively. Their main clinical symptoms were hypocalcemic convulsions, unusual facies (hyperthelorism, low set prominent ears, micrognathia, short philtrum) and cardiac malformations (vascular ring with right aortic arc, aberrant left innominated artery and ligamentum arteriosus in one of them and Tetralogy of Fallot with pulmonary valve atresia in the other). The first patient is now a 3.5 year old boy, his vascular ring was repaired and he has hypoparathyroidism but no clinical nor laboratory evidence of cellular immunodeficiency. The other patient had evidence of heart failure at her second week of life, she died at age sixteen days and, at necropsy, Fallot's tetralogy with pulmonary valve atresia, closed ductus arteriosus, histologically normal ectopic thymus and absent parathyroid glands were demonstrated. We postulate that these cases correspond to partial forms of Di George syndrome.

[Chronic hemorrhagic cystitis induced by cyclophosphamide in dermatomyositis refractory to corticosteroid treatment]. / Cistitis crónica hemorrágica por ciclofosfamida en dermatomiositis refractaria a tratamiento esteroidal.

Dermatomyositis was diagnosed at age 7 years to a fourteen year old female. The disease was unresponsive to high doses of prednisone, so she was treated with oral cyclophosphamide 0.8 mg.kg.day (25 mg.m2) but treatment was withheld after sixteen weeks because of hemorrhagic cystitis and changed to azathioprine for two years, which resulted in complete remission of dermatomyositis. Nevertheless silent microscopic hematuria persisted and chronic cystitis was demonstrated by cystoscopy and vesical biopsy at age 13 years. In this case chronic cystitis developed earlier and at lower doses of cyclophosphamide than in other previously reported cases.

[Cutaneous response to 2 and 10 units of tuberculin in infants]. / Respuesta cutánea de lactantes a 2 y 10 unidades de tuberculina.

A study was done in 322 healthy, well nourished infants, 3 to 18 months old from day care centers of metropolitan Santiago, Chile, that were given BCG immunization in their neonatal period: 304 (94.4%) of them showed BCG scars and were included in a double blind open study, to determine the cutaneous responses to 2 TU and 10 TU tuberculin (PPD). There were no differences in the mean size of cutaneous reactions nor in percent positive responses (greater than or equal to 10 mm), but cutaneous reactions greater than or equal to 15 mm were more frequent in infants tested with PPD 10 TU. In 184 out of 304 infants (60.5%) tuberculin reactions were negative (less than or equal to 10 mm). Eighteen out of 322 infants (5.6%) that didn't show BCG scars were injected with PPD 2 TU: tuberculin reactions sized 6 to 9 mm were recorded in 3/18 of these infants but none of them attained 10 mm. Fifty five infants whose tuberculin reactions were 5 mm or less were retested: a booster effect was likely from the appearance of enhanced dermal response after a second tuberculin test done with the same or higher tuberculin strength than the first one in 12/47 of these infants with BCG scar (25%) and in only 1/8 such subjects without BCG scar.

[Myelogram in systemic juvenile rheumatoid arthritis]. / Mielograma en artritis reumatoidea juvenil sistémica.

A retrospective study was done to evaluate bone marrow smears in seven children with systemic onset juvenile rheumatoid arthritis (JRA). Eosinophilia and monocytosis were found in all the patients and in five there also were increased proportions of mononuclear basophils. Anemia is common in this disease and erythroid hypoplasia was present in six cases. Four patients had increased numbers of plasma cells and three had histiocytes with hemophagocytic activity. We did not find hemophagocytosis, as reported before, in bone marrow smears of JRA patients.

Serum IgA deficiency induced by prolonged phenytoin treatment.

In a longitudinal study we have evaluated several immunological parameters in thirty three epileptic children and adolescents 4 to 14 years old treated with phenytoin, and matched normal controls. The patients had significantly lower levels than normal controls of IgA (153 +/- 89 vs 236 +/- 128 mg/dL p less than 0.001) and IgM (155 +/- 58 vs 217 +/- 105 mg/dL p less than 0.01). The decrease in serum IgA levels correlated with the length of treatment (r = 0.44, p less than 0.03). Eight of the patients had IgA deficiency. In 7 of these children, T lymphocytes subpopulations were determined. The results did not differ significantly from the matched controls.

Lupus eritematoso diseminado en la infancia. Estudio clinico y de sobrevida en 31 casos. / Lupus erythematosus disseminatus in childhood. Clinical study and survival in 31 cases

Se efectuo un analisis clinico y evolutivo de 31 pacientes portadores de lupus eritematoso diseminado (LED) de manera retrospectiva. Todos los sujetos eran a menores de 16 anos de edad y reunian como minimo 4 de los requisitos exigidos por la Academia Reumatologica Americana (ARA) para el diagnostico de la enfermedad.De los 31 pacientes, 26 pertenecieron al sexo femenino y 5 al masculino. Las principales manifestaciones clinicas y de laboratorio fueron semejantes a las descritas para el LED de tipo adulto, predominando las lesiones articulares y cutaneas.Se subraya la contribucion de las nuevas tecnicas inmunologicas en el diagnostico y evolucion de la enfermedad, especialmente de los AAN y AADN. La sobrevida global en nuestros enfermos alcanzo a 68 y 40% en 5 y 10 anos respectivamente, disminuyendo a 57 y 28% en los que sufrian nefropatia lupica. Los enfermos sin lesion renal, tuvieron 90% de sobrevida durante el periodo de observacion de 10 anos. Se analiza el impacto de los distintos tratamientos en la enfermedad y sugiere que el uso de combinaciones de esteroides suprarrenales con inmunosupresores, pudiera reducir la elevada mortalidad observada en estos pacientes

Anemia autoinmune y trombopenia en enfermedad mixta del tejido conectivo. / Autoimmune anemia and thrombocytopenia in mixed connective tissue disease

Se presenta un varon de seis anos, portador de enfermedad mixta del tejido conectivo (EMTC). Las manifestaciones iniciales fueron: anemia hemolitica Coomb positivo, trombopenia, artritis y hepatoesplenomegalia. La busqueda de anticuerpos dirigidos contra un antigeno soluble (ENA) dio resultados positivos contra una ribonucleoproteina (RNP) de origem nuclear. El paciente mejoro en coincidencia con el empleo de prednisona. No encontramos en la literatura otra comunicacion de EMTC con esta forma de comienzo en ninos. Se revista las manifestaciones clinicas, examenes de laboratorio y tratamiento de la EMTC en ninos