Maria D. Perez

Congenital heart block: development of late-onset cardiomyopathy, a previously underappreciated sequela.

OBJECTIVE We report 16 infants with complete congenital heart block (CHB) who developed late-onset dilated cardiomyopathy despite early institution of cardiac pacing. BACKGROUND Isolated CHB has an excellent prognosis following pacemaker implantation. Most early deaths result from delayed initiation of pacing therapy or hemodynamic abnormalities associated with congenital heart defects. METHODS A multi-institutional study was performed to identify common clinical features and possible risk factors associated with late-onset dilated cardiomyopathy in patients born with congenital CHB. RESULTS Congenital heart block was diagnosed in utero in 12 patients and at birth in four patients. Ten of 16 patients had serologic findings consistent with neonatal lupus syndrome (NLS). A pericardial effusion was evident on fetal ultrasound in six patients. In utero determination of left ventricular (LV) function was normal in all. Following birth, one infant exhibited a rash consistent with NLS and two had elevated hepatic transaminases and transient thrombocytopenia. In the early postnatal period, LV function was normal in 15 patients (shortening fraction [SF] = 34 +/- 7%) and was decreased in one (SF = 20%). A cardiac pacemaker was implanted during the first two weeks of life in 15 patients and at seven months in one patient. Left ventricular function significantly decreased during follow-up (14 days to 9.3 years, SF = 9% +/- 5%). Twelve of 16 patients developed congestive heart failure before age 24 months. Myocardial biopsy revealed hypertrophy in 11 patients, interstitial fibrosis in 11 patients, and myocyte degeneration in two patients. Clinical status during follow-up was guarded: four patients died from congestive heart failure; seven required cardiac transplantation; one was awaiting cardiac transplantation; and four exhibited recovery of SF (31 +/- 2%). CONCLUSIONS Despite early institution of cardiac pacing, some infants with CHB develop LV cardiomyopathy. Patients with CHB require close follow-up not only of their cardiac rate and rhythm, but also ventricular function.

Development of validated disease activity and damage indices for the juvenile idiopathic inflammatory myopathies: II. The childhood myositis assessment scale (CMAS): a quantitative tool for the evaluation of muscle function

OBJECTIVE To develop, validate, and determine the measurement characteristics of a quantitative tool for assessing the severity of muscle involvement in children with idiopathic inflammatory myopathies. METHODS The Childhood Myositis Assessment Scale (CMAS) was developed from 2 existing observational functional assessment tools to assess muscle function in the areas of strength and endurance across a wide range of ability and ages. The 14 ordinal items included were chosen to assess primarily axial and proximal muscle groups and are ranked with standard performance and scoring methods. Following the development of the CMAS, a training video and written instructions were developed and reviewed by the physicians participating in this study. Subsequently, utilizing a randomized block design, 12 physicians independently scored 10 children (9 with dermatomyositis, 1 with polymyositis; ages 4-15 years) twice in one day (morning and afternoon) on the CMAS. A pediatric physical therapist performed quantitative manual muscle strength testing (MMT) twice on each child (morning and afternoon), including the neck, trunk, and proximal and distal extremity muscle groups. RESULTS The CMAS has a potential range of 0-51, with higher scores indicating greater muscle strength and endurance. The observed mean for the 10 patients was 36.4 (median 44, SD 14.1, observed range 5-51). The total score for the CMAS correlated with the physicians global assessment (by visual analog scale) of disease activity, the MMT score, serum creatine kinase level, and the Juvenile Arthritis Functional Assessment Report score. The score on the CMAS was not correlated with patient age. Interrater reliability (Kendalls coefficient of concordance) ranged from 0.77 to 1.0 for individual items (all P < 0.001), and overall, it was 0.95 (P < 0.001). Intrarater reliability for the individual physicians was measured by correlation of the CMAS scores for each patient on 2 separate evaluations and ranged from 0.97 to 0.99, with an overall correlation for all physicians of 0.98 (all P < 0.001). CONCLUSION The CMAS demonstrated an acceptable range of observed scores, excellent convergent validity, and excellent inter- and intrarater reliability. The CMAS is validated to quantitatively assess muscle function in the areas of strength and endurance in children with idiopathic inflammatory myopathies. It can be used in routine clinical care as well as therapeutic trials.

Z Score Prediction Model for Assessment of Bone Mineral Content in Pediatric Diseases

The objective of this study was to develop an anthropometry‐based prediction model for the assessment of bone mineral content (BMC) in children. Dual‐energy X‐ray absorptiometry (DXA) was used to measure whole‐body BMC in a heterogeneous cohort of 982 healthy children, aged 5–18 years, from three ethnic groups (407 European‐ American [EA], 285 black, and 290 Mexican‐American [MA]). The best model was based on log transformations of BMC and height, adjusted for age, gender, and ethnicity. The mean ± SD for the measured/predicted ln ratio was 1.000 ± 0.017 for the calibration population. The model was verified in a second independent group of 588 healthy children (measured/predicted ln ratio = 1.000 ± 0.018). For clinical use, the ratio values were converted to a standardized Z score scale. The whole‐body BMC status of 106 children with various diseases (42 cystic fibrosis [CF], 29 juvenile dermatomyositis [JDM], 15 liver disease [LD], 6 Rett syndrome [RS], and 14 human immunodeficiency virus [HIV]) was evaluated. Thirty‐nine patients had Z scores less than −1.5, which suggest low bone mineral mass. Furthermore, 22 of these patients had severe abnormalities as indicated by Z scores less than −2.5. These preliminary findings indicate that the prediction model should prove useful in determining potential bone mineral deficits in individual pediatric patients.

Preliminary validation and clinical meaning of the cutaneous assessment tool in juvenile dermatomyositis

OBJECTIVE To provide preliminary validation of the Cutaneous Assessment Tool (CAT), a new tool to assess cutaneous manifestations of juvenile dermatomyositis (DM), and to explore the clinical meaning of CAT scores. METHODS Children with juvenile DM (n = 113) were assessed at baseline and 7-9 months later (n = 94). Internal consistency, redundancy, construct validity, and responsiveness of the CAT were examined. CAT scores corresponding to ordinal global assessments were determined. RESULTS Item-total correlations ranged from 0.27-0.67 for activity lesions present in > or =10% of patients; item-domain and domain-total correlations ranged from 0.25-0.99. Cronbachs alpha was 0.79 for the CAT activity score and 0.74 for the CAT damage score. As predicted, the CAT activity score correlated strongly with both global disease activity and skin disease activity and moderately with the Childhood Myositis Assessment Scale, whereas the CAT damage score correlated moderately with the physician global disease and skin disease damage scores. Median CAT activity scores of 1, 7, 13, 18, and 31 corresponded to absent, mild, moderate, severe, and extremely severe skin disease activity, respectively. Median CAT damage scores of 0, 1, 2, and 5 correlated with the same descriptions of damage (severe and extremely severe combined). CONCLUSION Preliminary validation of the CAT demonstrated good internal consistency, nonredundancy, good construct validity, and appropriate responsiveness. The CAT is a comprehensive, semiquantitative assessment tool for skin disease in juvenile DM.

Cardiovascular calcifications in pediatric patients receiving maintenance dialysis

Cardiovascular disease is a major cause of morbidity and mortality in adult patients with end-stage renal disease receiving maintenance dialysis. Coronary artery calcifications (CAC) contribute to the high prevalence of cardiac disease and are associated with hyperphosphatemia, an elevated calcium-phosphorus product (CaxP), and prolonged time on dialysis. Chronic inflammation and malnutrition are also associated with an increased risk for development of cardiac calcifications. Young adults receiving maintenance dialysis develop cardiac calcifications at a degree out of proportion to healthy adults of the same age and gender. Many of these young adults initiated dialysis as children or teenagers. Risk factors associated with the development of CAC are also seen in the pediatric dialysis population. To date, reports of cardiac calcifications in pediatric patients receiving maintenance dialysis are limited to post-mortem studies. We present two pediatric patients with ANCA-positive vasculitis diagnosed with cardiac calcifications while receiving maintenance dialysis. Hyperphosphatemia and an elevated CaxP product were seen in both patients and probably contributed to the development of extraskeletal calcifications. In addition, both patients had an underlying systemic inflammatory disease and significant weight loss/malnutrition that may have contributed to the early and rapid onset of cardiac calcifications.

Juvenile onset central nervous system folate deficiency and rheumatoid arthritis.

Isolated cerebral folate deficiency was detected in a 13-year-old girl with cognitive and motor difficulties and juvenile rheumatoid arthritis. Her serum contains autoantibodies that block membrane-bound folate receptors that are on the choroid plexus and diminish the uptake of folate into the spinal fluid. Whereas her serum folate exceeded 21 ng/mL, her spinal fluid contained 3.2 ng/mL of 5-methyltetrahydrofolate as a consequence of the autoantibodies diminishing the uptake of this folate.

Pediatric rheumatic diseases

The rheumatic diseases of childhood are a relatively common and extraordinarily diverse group of illnesses; nevertheless, they are at least distantly related by similarities of immunodysregulation. These pathophysiologic relationships are reflected in affected children in similarities of historical, physical, and laboratory data as well as therapeutic intervention.

Features distinguishing clinically amyopathic juvenile dermatomyositis from juvenile dermatomyositis

Objective We examined features of clinically amyopathic JDM (CAJDM), in which patients have characteristic rashes with little to no evidence of muscle involvement, to determine whether this is a distinct phenotype from JDM. Methods Demographic, clinical, laboratory and treatment data from 12 (9 hypomyopathic, 3 amyopathic) patients meeting modified Sontheimer criteria for CAJDM and from 60 matched JDM patients meeting Bohan and Peter criteria were examined. Differences were evaluated by Fishers exact and Mann-Whitney tests, random forests and logistic regression analysis. Results Nine (75%) CAJDM patients had anti-p155/140 (transcriptional intermediary factor 1), one (8.3%) anti-melanoma differentiation-associated gene 5 autoantibodies and two (16.7%) were myositis autoantibody negative. CAJDM patients were younger at diagnosis and frequently had mild disease at onset. CAJDM patients had less frequent myalgias, arthritis, contractures, calcinosis, dysphagia, abdominal pain and fatigue. The muscle, skeletal and overall clinical scores were lower in CAJDM. Serum muscle enzymes were less frequently increased in CAJDM, and peak values were lower. CAJDM patients received fewer medications compared with JDM patients. Only 50% of CAJDM patients received oral prednisone, but the maximum dose and treatment duration did not differ from JDM. At a median follow-up of 2.9 years, CAJDM patients had no documented functional disability, and none developed weakness, calcinosis, interstitial lung disease or lipodystrophy. Multivariable modelling revealed a lower skeletal score and less frequent myalgias as the most important factors in distinguishing CAJDM from JDM. Conclusion CAJDM may be distinguished from JDM, in that they often have p155/140 (transcriptional intermediary factor 1) autoantibodies, have fewer systemic manifestations and receive less therapy.

T-CELL RECEPTOR EXCISION CIRCLES: A NOVEL APPROACH TO IDENTIFY IMMUNODEFICIENCY IN NEWBORNS WITH CONGENITAL HEART DISEASE

Routine childhood infections in patients with congenital heart disease (CHD) are a risk factor for morbidity and death. T-cell Receptor Excision Circles (TRECs) are an established biomarker of T-cell lymphopoiesis and low TREC levels are a marker for Severe Combined Immunodeficiency (SCID). False

Iron Metabolism in Children with Juvenile Rheumatoid Arthritis (JRA).2

Background: The etiology of chronic anemia in children with JRA is poorly understood. We utilized stable and radioactive Fe isotopes to determine Fe absorption, RBC incorporation and intraarticular deposition in children with JRA.