Effect of 2-6 weeks of systemic steroids on bone mineral density in children.

BACKGROUND: The use of systemic steroids for 6+ weeks in children is associated with decreased bone mineral content (BMC) and density (BMD). However, the effects of a shorter duration of use on BMD are unknown. PURPOSE: To determine the effect of the use of systemic steroids for 2-6 weeks on BMD and BMC in pediatric patients. METHODS: Twenty-five pediatric patients (21 with tuberculosis, 2 with systemic juvenile idiopathic arthritis, 1 with inflammatory bowel disease, 1 with autoimmune hemolytic anemia) who received systemic steroids for 2-6 weeks and 25 age- and sexmatched controls were enrolled. BMC, BMD, and z scores of the whole body (WB), lumbar spine (LS), nondominant distal radius (DR), and total body less the head (TBLH) were determined by dual-energy x-ray absorptiometry at baseline, the end of steroid therapy or 6 weeks (whichever was earlier; first follow-up), and at the end of 3 months from baseline (second follow-up) in patients and at baseline in controls. The values were adjusted for confounding variables. Continuous and categorical variables were compared using Student t test and the chi-square test or Fisher exact test, respectively. Pairwise comparisons employed Bonferroni correction. RESULTS: Statistically significant decreases in BMC, BMD, and all z scores were observed. BMC declined by 5.37%, 2.08%, 1.82%, and 2.27%, and 11.42%, 3.75%, 3.34%, and 4.17% for WB, LS, DR, and TBLH, respectively, at the first and second follow-ups, respectively. Similarly, BMD declined by 2.01%, 2.31%, 2.18%, and 1.70% and 4.59%, 3.76%, 3.14%, and 3.50% for the WB, LS, DR, and TBLH, respectively, at the first and second follow-ups, respectively. A significant negative correlation was found among bone densitometric parameters, duration, and cumulative dose. CONCLUSION: The use of systemic steroids for 2-6 weeks in pediatric patients decreased the BMD and BMC of trabecular and cortical bones, an effect that persisted after discontinuation.

Magnetic resonance imaging findings in the sternoclavicular joint in juvenile idiopathic arthritis and comparison with clinical examination.

OBJECTIVE: The sternoclavicular joint (SCJ), an important link between the appendicular and axial skeleton, though involved in 41% of rheumatoid arthritis patients, has not been studied in juvenile idiopathic arthritis (JIA). Hence, this cross-sectional study was done to delineate the magnetic resonance imaging (MRI) findings in SCJ in JIA and compare with the clinical examination to diagnose SCJ arthritis. METHODS: Of the 116 JIA patients attending the pediatric rheumatology clinic, twenty-one patients (42 SC joints) were evaluated by 1.5 T MRI using the four components of early and late inflammatory changes-synovial hypertrophy, bone marrow edema (BME), cartilage lesions, and bone erosions. Results were compared with clinical assessment of SCJ arthritis. RESULTS: Of the 42 SCJ evaluated (21/116 patients), MRI changes were seen in 27 SCJs (15 patients, 12.9% of 116 JIA patients). Early MRI changes were seen in 60% of joints found normal on clinical examination, with as much as 1/4th of them revealing late destructive changes. Synovial hypertrophy, BME, cartilage lesions, and bone erosions were seen in 5, 15, 4, and 10 patients, respectively. Sensitivity and specificity of clinical examinations to evaluate SC joint involvement were 55.5% and 53.3%, respectively. CONCLUSION: MRI evaluation of the SCJ in JIA revealed findings in 15/21 enrolled patients. BME, bone erosions, synovial hypertrophy, and cartilage lesions were seen in 15, 10, 5, and 4 enrolled patients, respectively. Clinical examination was found to be neither sensitive nor specific. Key Points • MRI could delineate both early and late inflammatory changes in SCJ in JIA. BME, bone erosions, synovial hypertrophy, and cartilage lesions were seen in 15, 10, 5, and 4 enrolled patients, respectively. • The frequency of SC joint involvement in JIA was at least 12.9% of patients in our study. • Clinical examination for evaluating SC joint arthritis has low sensitivity (55.5%) and specificity (53.3%).

Evaluation of enthesitis in patients with juvenile idiopathic arthritis by power color and spectral Doppler ultrasonography.

OBJECTIVE: Ultrasonography in patients with juvenile idiopathic arthritis (JIA) could potentially be useful for evaluation of enthesitis. The aim of this study was to evaluate enthesitis in patients with JIA quantitatively by power color and spectral Doppler ultrasonography by determining color fraction (CF) and resistive index (RI). METHODS: A cross-sectional single-center study was performed in 15 (61 entheseal sites) patients with JIA with clinical enthesitis. A total of 9 age and sex matched healthy controls (53 entheseal sites) were also examined and compared. Entheseal sites (quadriceps tendon, patellar tendon, tendo-Achilles, medial and lateral epicondyles of humerus) were examined on USG B mode for tendon thickening, hypo- and hyper-echogenicity, enthesophytes, and cortical erosions/irregularities by power Doppler ultrasound for the presence of Doppler signal and by power color Doppler and spectral Doppler ultrasonography to derive CF and RI respectively. RESULTS: The mean thickness of entheseal site in patients and controls were 3.55±0.82 mm and 2.8±0.37 mm, respectively (p<0.001). The power Doppler signal was present in 93.4% of patients (p<0.001). The pooled data of all entheseal sites revealed a significantly higher CF in patients (0.08±0.03) than in controls (0.006±0.008) (p<0.001). The mean RI in patients (0.61±0.09) was significantly lower than that in controls (0.92±0.12) (p<0.001). The cut-off of RI (0.7) and CF (0.029) determined by receiver operating curve analysis revealed a diagnostic accuracy of 94.7% and 96.5%, respectively. CONCLUSION: Evaluation of enthesitis by determining CF and RI via power color Doppler and spectral Doppler is possible in JIA patients.

Pre-eclampsia: Molecular events to biomarkers.

Pre-eclampsia is a hypertensive disorder in pregnancy, which accounts for 10-15% of the maternal and perinatal mortality worldwide. Abnormal placental development and tissue hypoxia are its main etiologic factors. The present diagnostic methods of blood pressure monitoring and renal function evaluation are insufficient in the early detection of pre-eclampsia. Since molecular events portent well ahead of the disease onset, biomarker research for the early diagnosis of pre-eclampsia has recently generated ambitious clinical targets. However, no clinically validated biomarker has so far been reported for the prediction of pre-eclampsia. Therefore, this review takes stock of the current understanding of pre-eclampsia from a molecular biology perspective and critically evaluates the following diagnostic potentials claimed for the biomarkers: placental proteins, angiogenic markers, and cell-free fetal DNA (cffDNA) in maternal circulation. Though the emerging evidences in favor of the fetal-specific epigenetic marker, hypermethylated RASSF1A of cffDNA, are highlighted, it pitches for a broader strategy of 'combination biomarker approach' for the reliable forecasting and triaging of pre-eclampsia.

Power Color Doppler and Spectral Doppler Ultrasonography to Evaluate Response to Intra-articular Steroid Injection in Knee Joints in Juvenile Idiopathic Arthritis.

OBJECTIVE: To evaluate the role of ultrasonographic indices (Color Fraction and Resistive Index) in assessing the effect of intra-articular steroid (IAS) injection on synovial inflammation in knee joints of Juvenile Idiopathic Arthritis (JIA) patients and to determine the correlation between these ultrasonographic indices and clinical and laboratory parameters in JIA patients after IAS. METHODS: Twenty seven patients of JIA and equal number of age and sex matched healthy controls were enrolled. Thirty six knee joints were injected with IAS. Duration of morning stiffness, swelling score, tenderness score, range of motion, visual analogue scale for pain, Physician global assessment of disease activity, Patient/Parent assessment of general well being, Juvenile Arthritis Disease Activity Score, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), synovial thickness, synovial effusion, Color fraction (CF) and Resistive index (RI) were measured at base line and at one and two months of follow-up. RESULTS: At baseline, a significant difference was found in ESR, CRP, CF and RI values between cases and controls. A significant decrease in various clinical, core set variables and ultrasonographic parameters was observed at each follow-up. Synovial thickness, synovial effusion and CF decreased by 51.78%, 64.67% and 49.35% respectively and range of motion and RI increased by 166% and 31.94% respectively at second follow-up. Both CF and RI showed a significant correlation with active joint count. Both CF and RI had a high inter and intra-class correlation. CONCLUSIONS: Power Color Doppler and Spectral Doppler ultrasonographic indices (CF and RI) may have a role in assessment of the response to IAS injection of inflamed knee joints.

Idiopathic musculoskeletal pain in Indian children-Prevalence and impact on daily routine.

OBJECTIVES: To study the prevalence of idiopathic musculoskeletal pain (IMSP) in school going children and its impact on daily life. METHODS: One thousand eighteen apparently healthy school children aged 5-16 years were assessed and analysed for IMSP and its associated problems. Standard tests for significance were applied. RESULTS: One hundred and sixty-five (16.2%) children mostly males (55.2%) reported IMSP. Lower limbs (52.1%) were the most common location of pain. More than 1 year of pain history was present in 15%. Thirty-seven percent children complained of discomfort during walking, 30.9%, had pain during physical exercise, 29.2% had difficulty attending lessons and 4.2% had interference in pursuing hobbies. The children were also further sub grouped into preadolescents and adolescents. There was significant difference in pain duration and duration of each pain episode in the two groups (p=0.01). A significant number of children (21.2%) with IMSP reported school absenteeism (p<0.001). A significant number of adolescents had history positive for contact sports (p=0.001). Sleep disturbances were also reported to be higher in children with IMSP (29% vs. 5.7%, p=0.001). Other associated problems in children with IMSP found were day time tiredness (51.1%), headache (47.3%) and abdominal pain (24.8%). CONCLUSIONS: Prevalence of IMSP in school children aged 5-16 yrs was found to be 16.2% and a significant percentage of these children experience interference with daily activities including school absenteeism.

Idiopathic Musculoskeletal Pain in Indian children-Prevalence and Impact on Daily Routine / Prevalência e impacto nas atividades diárias da dor musculoesquelética idiopática em crianças da Índia

ABSTRACT Objectives: To study the prevalence of idiopathic musculoskeletal pain (IMSP) in school going children and its impact on daily life. Methods: One thousand eighteen apparently healthy school children aged 5–16 years were assessed and analysed for IMSP and its associated problems. Standard tests for significance were applied. Results: One hundred and sixty-five (16.2%) children mostly males (55.2%) reported IMSP. Lower limbs (52.1%) were the most common location of pain. More than 1 year of pain history was present in 15%. Thirty-seven percent children complained of discomfort during walking, 30.9%, had pain during physical exercise, 29.2% had difficulty attending lessons and 4.2% had interference in pursuing hobbies. The children were also further sub grouped into preadolescents and adolescents. There was significant difference in pain duration and duration of each pain episode in the two groups (p = 0.01). A significant number of children (21.2%) with IMSP reported school absenteeism (p < 0.001). A significant number of adolescents had history positive for contact sports (p = 0.001). Sleep disturbances were also reported to be higher in children with IMSP (29% vs. 5.7%, p = 0.001). Other associated problems in children with IMSP found were day time tiredness (51.1%), headache (47.3%) and abdominal pain (24.8%). Conclusions: Prevalence of IMSP in school children aged 5–16 yrs was found to be 16.2% and a significant percentage of these children experience interference with daily activities including school absenteeism.

RESUMO Objetivos: Estudar a prevalência de dor musculoesquelética idiopática (DMEI) em crianças em idade escolar e seu impacto nas atividades diárias. Métodos: Foram avaliadas e analisadas 1.018 crianças em idade escolar aparentemente saudáveis entre cinco e 16 anos quanto à presença de DMEI e seus problemas associados. Foram aplicados os testes de significância padrão. Resultados: Relataram DMEI 165 (16,2%) crianças, em sua maior parte do sexo masculino (55,2%). Os membros inferiores (52,1%) foram a localização mais comum da dor. A história de dor presente havia mais de um ano foi encontrada em 15% das crianças; 37% delas queixaram-se de desconforto durante a caminhada, 30,9%, tinham dor durante o exercício físico, 29,2% tinham dificuldade de frequentar as aulas e 4,2% sofriam interferência na participação em passatempos. As crianças foram ainda subagrupadas em pré-adolescentes e adolescentes. Houve diferença estatisticamente significativa na duração da dor e na duração de cada episódio de dor nos dois grupos (p = 0,01). Uma quantidade significativa de crianças com DMEI (21,2%) relatou absentismo escolar (p < 0,001). Uma quantidade significativa de adolescentes tinha história positiva de prática de esportes de contato (p = 0,001). Os distúrbios do sono também foram relatados como maiores em crianças com DMEI (29% vs. 5,7%, p = 0,001). Outros problemas associados encontrados em crianças com DMEI foram o cansaço durante o dia (51,1%), a cefaleia (47,3%) e a dor abdominal (24,8%). Conclusões: A prevalência de DMEI encontrada em crianças entre cinco e 16 anos foi de 16,2%. Uma percentagem significativa dessas crianças relata interferência nas atividades diárias, incluindo absentismo escolar.

Evaluation of fetal hypermethylated RASSF1A in pre-eclampsia and its relationship with placental protein-13, pregnancy associated plasma protein-A and urine protein.

OBJECTIVES: Cell free fetal DNA (cffDNA) and its hypermethylated RASSF1A gene signify a recent advancement in non-invasive prenatal diagnosis of feto-placental anomalies like pre-eclampsia. The study uses hypermethylated RASSF1A gene to quantify cffDNA and to assess its relationship with placental and urine proteins in pre-eclampsia cases. DESIGN AND METHODS: DNA was isolated from plasma samples of clinically diagnosed cases of pre-eclampsia (n=103) and normal pregnancy (n=616) from 21weeks of gestation. Through methylation sensitive enzyme (BstUI) digestion; followed by real time-polymerase chain reaction (RT-PCR), quantification of hypermethylated RASSF1A was done. Immunoassays determined: placental protein-13 (pp-13) and pregnancy associated plasma protein A (PAPP-A) and pyrogallol red molybdate assay for 24h urine protein. RESULTS: Highly significant differences between control and pre-eclampsia cases for hypermethylated RASSF1A concentrations were found; Group I: 33±7.35 vs 74.46±16.71, Group II: 53.75±16.65 vs 244.22±35.68, Group III: 93.25±19.08 vs 412.31±80.18, Group IV: 144.30±18.13 vs 1056.89±153.78, Group V: 307.55±40.76 vs 2763.76±259.76copies/ml. Multivariate Pearson's correlation analysis of hypermethylated RASSF1A with pp-13, PAPP-A and urine proteins showed positive and very highly significant (P<0.001) associations. CONCLUSIONS: Diagnostic potential of fetal specific, hypermethylated RASSF1A was evaluated. Its positive relationship with placental and urine proteins submit the case for considering it as a reliable marker for pre-eclampsia.

[Idiopathic musculoskeletal pain in Indian Children-prevalence and impact on daily routine]. / Prevalência e impacto nas atividades diárias da dor musculoesquelética idiopática em crianças da Índia.

OBJECTIVES: To study the prevalence of idiopathic musculoskeletal pain (IMSP) in school going children and its impact on daily life. METHODS: One thousand eighteen apparently healthy school children aged 5-16 years were assessed and analysed for IMSP and its associated problems. Standard tests for significance were applied. RESULTS: One hundred and sixty five (16.2%) children mostly males (55.2%) reported IMSP. Lower limbs (52.1%) were the most common location of pain. More than 1 year of pain history was present in 15%. Thirty seven percent children complained of discomfort during walking, 30.9%, had pain during physical exercise, 29.2% had difficulty attending lessons and 4.2% had interference in pursuing hobbies. The children were also further sub grouped into preadolescents and adolescents. There was significant difference in pain duration and duration of each pain episode in the two groups (p=0.01). A significant number of children (21.2%) with IMSP reported school absenteeism (p<0.001). A significant number of adolescents had history positive for contact sports (p=0.001). Sleep disturbances were also reported to be higher in children with IMSP (29% vs. 5.7%, p=0.001). Other associated problems in children with IMSP found were day time tiredness (51.1%), headache (47.3%) and abdominal pain (24.8%). CONCLUSIONS: Prevalence of IMSP in school children aged 5-16 yrs was found to be 16.2% and a significant percentage of these children experience interference with daily activities including school absenteeism.

Lipodystrophy syndrome among HIV infected children on highly active antiretroviral therapy in northern India.

BACKGROUND: It is estimated that about 2.5 million people are living with HIV infection in India. Although antiretroviral drugs have been able to reduce the mortality, these drugs have serious side effects one of which is lipodystrophy syndrome. Most of the drugs used in HAART viz, protease inhibitors, stavudine and nevirapine are associated with lipodystrophy. Hence we conducted this study to assess the prevalence of lipodystrophy in HIV infected children on HAART and its associated risk factors. MATERIALS AND METHODS: A cross sectional study was conducted on 80 HIV infected children aged 2-18 years of age who were on stavudine based HAART for ≥ 2 years. These children were assessed for presence of lipodystrophy, its metabolic complications and associated risk factors. RESULTS: Lipodystrophy was observed in 33.7% of children with lipoatrophy being the commonest subtype followed by lipohypertrophy. Older age, increased duration of treatment and dyslipidaemia were found to be associated in patients with lipodystrophy than those without. On further multivariate analysis of independent risk factors only increased duration of treatment was significantly associated with lipodystrophy. No association was found with insulin resistance. CONCLUSION: We observed that lipodystrophy is a common finding in HIV patients treated with HAART for long duration.

Measurement of bone mineral density by dual energy X-ray absorptiometry in juvenile idiopathic arthritis.

OBJECTIVE: To evaluate bone mineral density using dual X-ray absorptiometry in Juvenile Idiopathic Arthritis (JIA) patients and factors affecting it, if any. METHODS: A cross sectional study was conducted by enrolling thirty five patients of JIA and age and sex matched controls. Bone Mineral Density (BMD) and Z score of whole body, total body less head, lumbar spine and distal radius were obtained and adjusted for age, sex, weight and BMI in both cases and controls. Dietary intake of calcium, vitamin D intake, sunlight exposure, weight bearing physical activity, age of onset, duration of disease, disease activity score and treatment received (prednisolone and methotrexate) were recorded. RESULTS: BMD was significantly lower among patients as compared to controls. Decreased dietary intake of vitamin D and calcium, decreased weight bearing physical activity and sunlight exposure were the major factors for low BMD. Use of steroid also decreased BMD to some extent, whereas use of methotrexate, disease duration and severity did not have a significant correlation with BMD. CONCLUSIONS: Apart from disease control, it is important to improve the dietary intake of calcium, vitamin D and encourage more physical activities and exposure to sunlight in JIA patients.

Evaluation of synovial inflammation in juvenile idiopathic arthritis by power color Doppler and Spectral Doppler ultrasonography.

OBJECTIVES: To compare Power Color Doppler and Spectral Doppler ultrasonography indices (Resistive index and color fraction) in cases of Juvenile Idiopathic Arthritis (JIA) with healthy controls and evaluate their correlation with clinical and laboratory parameters. METHODS: A cross sectional study was done over a period of 16 mo. Thirty patients of JIA and 30 age and sex matched healthy children were enrolled. Swelling and tenderness scores were evaluated and hemoglobin, total leukocyte count, erythrocyte sedimentation rate and C-reactive protein were done. A total of 112 diseased joints and 135 healthy joints were evaluated by USG by the same radiologist, and color fraction and RI were recorded. RESULTS: Statistically significant higher color fraction and lower RI (Resistive Index) were found in diseased joints as compared to healthy joints. Also the value of color fraction increased significantly with increasing grade of tenderness and RI decreased significantly with increasing grade of swelling. CONCLUSIONS: Power Color Doppler and Spectral Doppler ultrasonography (USG) indices (RI and color fraction) are significantly different in JIA patients. These might find a place in early diagnosis, monitoring of disease activity and response to therapy in JIA patients.

Effect of glucocorticoids on serum lipid profile and endothelial function and arterial wall mechanics.

OBJECTIVE: To determine the effect of glucocorticoids on lipid profile, endothelial function and arterial wall mechanics in children. METHODS: Thirty patients who had received glucocorticoids for 4 to 8 wk were compared with 30 age and sex matched healthy controls. Baseline evaluation included weight, height, body mass index (BMI), blood pressure (BP), lipid profile and Ultrasonographic evaluation of brachial artery for endothelial dependant as well as endothelial independent vasodilatation and evaluation of common carotid artery for intima media thickness (IMT) and arterial wall mechanics. All of these parameters were evaluated two more times- after 4 wk of steroid therapy and 2 wk after stopping the drug. RESULTS: Patients were found to have significant increase in BMI; systolic and diastolic BP; total and LDL cholesterol and carotid IMT and also a decrease in cross sectional compliance (CSC) after 4 wk of steroid therapy (oral prednisolone). However, all these parameters returned towards baseline, 2 wk after stopping the drug. No endothelial dysfunction was observed in these patients. CONCLUSIONS: Four to eight wk of glucocorticoids use in children leads to reversible changes in BMI, systolic and diastolic BP, total and LDL cholesterol, carotid IMT and CSC.

Leflunomide in systemic onset Juvenile idiopathic arthritis.

Methotrexate, the mainstay of treatment in Juvenile idiopathic arthritis, might not be effective in a few patients of polyarticular and systemic onset juvenile idiopathic arthritis. Use of biologicals like TNF-a blockers, the next line of preferred drugs is constrained by the high cost. We successfully used leflunomide in four patients.

Risk factors of dengue shock syndrome in children.

This retrospective hospital-based study was conducted to evaluate the various risk factors associated with dengue shock syndrome (DSS) in patients (≤18 years of age) of dengue hemorrhagic fever (DHF). Medical records of these 483 patients with DHF (IgM serology positive) were analyzed with reference to shock for various clinical and biochemical parameters. Of the 483 children, 405 were categorized in DHF group (grade I, 282 children; grade II, 123 children) and 78 in DSS group (grade III, 59 children; grade IV, 19 children). Using univariate and multivariate logistic regression and p-value of <0.05 as significant, the presence of spontaneous bleeding, hepatomegaly, signs of capillary leakage like ascitis and pleural effusion, leucopenia <4000 mm(3) and age >5 years were found out to be significant risk factors of shock in pediatrics patients of DHF.