Bone strength in children with growing pains: long-term follow-up.

OBJECTIVES: To examine the changes in bone strength in a cohort of children with 'growing pains' (GP) after 5 years follow-up and the correlation with pain outcome. METHODS: Bone strength was measured by quantitative ultrasound. Subjects were 39 children with GP previously studied. Controls were normograms based on the measurement of bone speed of sound in 1085 healthy children. Current GP status was assessed by parental questionnaires. Bone strength was compared with pain outcome. RESULTS: We examined 30/39 (77%) patients after 5 years. Bone strength was significantly increased when compared to the first study (Z score 0.65±1.77 vs. -0.62±0.90, p<0.001). While overall there was no significant difference in the bone strength between the 16 (53%) patients whose GP resolved and the 14 (47%) who continued to have GP episodes (p=0.71), all 6 (20%) patients with a speed of sound Z-score <-1 continued to have GP (p=0.003). CONCLUSIONS: Our findings that pain improves in most patients parallel to the increase in bone strength may support the hypothesis of GP representing in some patients a local overuse syndrome.

Pharmacokinetics of colchicine in pediatric and adult patients with familial Mediterranean fever.

This study sought to determine the appropriate starting dose of colchicine in children aged 2 to 4 years with familial Mediterranean fever (FMF) based on steady-state pharmacokinetics in pediatric patients with FMF from 2 to less than 16 years and adult patients with FMF from 16 to 65 years. Outpatients received colchicine for 90 days starting with a fixed dose for 14 days (blood sampling days 14 and 15). After starting doses of colchicine (0.6 mg/day [2 to less than 4 years], 0.9 mg/day [from 4 to less than 6 years], 0.9 mg/day [from 6 to less than 12 years], 1.2 mg/day [from 12 to less than 16 years], and 1.2 mg/day [from 16 to less than 65 years]), the observed steady-state pharmacokinetic parameters were comparable across age groups, despite the higher doses of colchicine on a mg/kg/day basis in the younger age groups. An exception occurred with once-daily colchicine, whereby mean Cmax for colchicine was higher in patients 4 to less than 6 years (9.4 ng/mL) compared with the younger and older age groups (6.1-6.7 ng/mL). Mean AUC0?24h values in children 2 to less than 4, 6 to less than 12, and 12 to less than 16 years were similar to those in adults. However, mean AUC0?24h values in children 4 to less than 6 years were 25 percent higher than those observed in adults. The results show that the recommended starting dose for children 2-4 years and 4-6 years should be 0.6 mg/day (half the US adult dose). Children aged 6 to less than 12 years should receive 0.9 mg/day (i.e. three-quarters of the US adult dose). The safety of colchicine in children 2 to less than 4 years was comparable to that in older children and adults.

Relationship between health-related quality of life and SLE activity and damage in children over time.

We previously described the development and validation of the 'Simple Measure of the Impact of Lupus Erythematosus in Youngsters' (SMILEY) for the reliable assessment of health-related quality of life (HRQOL) in children with systemic lupus erythematosus (SLE). The objectives of this new study were to determine the relationship of SMILEY scores to patient's/parent's assessment of HRQOL and SLE status, and physician's assessment of disease activity and damage over time. In this multicentre study, 68 children with SLE and parents completed SMILEY including the global HRQOL and SLE status assessments, physicians completed disease activity and damage tools at two time-points. Spearman rho was calculated between SMILEY scores and other scales, and between interval changes in SMILEY scores and other scales. SMILEY scores correlated with patient/parent assessments of global HRQOL and SLE status, disease activity and damage, confirming previous findings. The change in disease activity and damage measures correlated most strongly with the changes in SMILEY domains, Limitation and Burden of SLE. Results provide preliminary evidence that Limitation and Burden of SLE domains of SMILEY reflect the impact of disease activity and damage on HRQOL.

Outcome of a national Israeli cohort of pediatric systemic lupus erythematosus.

The aim of this study was to describe the clinical manifestations and outcomes of a national cohort of childhood systemic lupus erythematosus (cSLE). All cases of cSLE registered in the Israeli national registry of children with rheumatic diseases between 1987-2003 were examined for disease activity and damage by the SLE disease activity index (SLEDAI) and SLE collaborating clinics/American College of Rheumatology (SLICC/ACR) damage index. Demographic, clinical, laboratory and treatment factors were analysed for their effect on the outcome. One-hundred and two patients were identified, 81% females, with a mean age at diagnosis of 13.3 +/- 2.6 years. The mean SLEDAI score was 17.2 +/- 9.0 (range 2-60). Fifty four patients were followed for at least five years. The mean SLEDAI decreased to 7.6 +/- 6.3 (0-29) and the mean SLICC/ACR damage index was 0.7 +/- 1.6 (0-8). Five patients developed chronic renal failure. No patients died. No factors were found to be significantly associated with the outcome except the initial SLEDAI score. The five-year outcome of our national cSLE cohort was good; with relatively low activity and minimal damage in most patients. The initial SLEDAI predicted the development of late damage.

Methotrexate/naproxen-associated severe hepatitis in a child with juvenile idiopathic arthritis.

Methotrexate (MTX) is a cornerstone in the treatment of juvenile idiopathic arthritis (JIA). Although associated with many mild adverse effects, the short and long-term safety of MTX in JIA has been excellent. While many JIA children treated with MTX develop liver enzyme abnormalities, no cases of irreversible liver damage or of severe non-infectious hepatitis with Reye-like features have been reported in non-systemic JIA. We report a 2-year-old girl with oligoarthritis whose liver enzyme increased to greater than 45 times the upper limit of normal, and developed hypoglycemia and hyperammonemia after 10 months of MTX and naproxen therapy. An infectious and metabolic work-up for other causes was unremarkable. She recovered completely after folinic acid therapy; MTX and naproxen was not restarted. While very rare in JIA, MTX in synergism with naproxen can induce severe liver toxicity and it is important to screen children for liver enzyme abnormalities.

Sarcoid-related uveitis occurring during etanercept therapy.

We report the case of a 7-year-old boy who was initially diagnosed as having polyarticular juvenile idiopathic arthritis. Clinical and laboratory features of overt sarcoidosis became evident early during etanercept therapy when he developed acute panuveitis, papular skin rash and elevated levels of angiotensin-converting enzyme. Non-caseating granulomas were present in the liver. Uveitis resolved upon discontinuation of etanercept and systemic administration of corticosteroids. In rare cases expression of autoimmune disorders or expanded clinical features of these disorders may occur during etanercept treatment.

"Unresolving pneumonia" as the main manifestation of atypical Kawasaki disease.

Two cases of atypical Kawasaki disease (KD) manifested as persistent lobar lung consolidation, prolonged fever, and active inflammatory laboratory markers unresponsive to antibiotic treatment are reported. One of the children developed a giant coronary aneurysm. Atypical KD should be considered in the differential diagnosis of young children with prolonged fever and lobar consolidation unresponsive to antibiotics.

Profile of a pediatric rheumatology practice in Israel.

BACKGROUND: Several studies from Western countries have analyzed the profile of pediatric rheumatology practices. Due to differences in demography and health care systems the profile in Israel may differ from those countries. OBJECTIVE: To describe the profile of a pediatric rheumatology practice in Israel. METHODS: All new patients seen during the course of 2000 as part of my pediatric rheumatology practice in Northern Israel were registered at their initial encounter. Recorded were demographic data, referral patterns, diagnoses, and disease-related data. Diagnoses were grouped together by types of condition. RESULTS: 242 new patients were seen. 39% of the patients had a rheumatic condition, 39% had non-inflammatory conditions, 12% had periodic fever syndromes and for 10% no definitive diagnosis was determined. 14% had chronic rheumatic diseases. The time until diagnosis was significantly greater and more physicians were involved in the evaluation of periodic fever syndromes than in other disease groups. Seventeen (7%) patients had juvenile rheumatoid arthritis (JRA). The minimum estimated incidence of JRA was 8.8 per 100,000 children. CONCLUSIONS: Most patients seen did not have classic inflammatory rheumatic diseases, similar to data from other Western countries. Distinctive to Israel and the Middle East, periodic fever syndromes comprise a large proportion of the pediatric rheumatology practice. These syndromes are relatively difficult for community physicians to diagnose.

The use of naproxen in the treatment of children with rheumatic fever.

We evaluated the efficacy and safety of naproxen (10-20 mg/kg/d) for the treatment of arthritis and fever related to rheumatic fever in 19 children. Fever and arthritis resolved within a median of 1 day of beginning treatment (range, 1-2 and 1-30 days, respectively). The sole patient with prolonged arthritis had small joint involvement. No gastrointestinal, dermatologic, liver, or renal side effects were observed. None of the patients developed carditis over the following 6 months. Naproxen appears to be effective for the treatment of arthritis and fever related to rheumatic fever and is well tolerated.

Relationship between serum glucose and injury severity score in childhood trauma.

PURPOSE: The aim of this study was to examine the relationship between initial serum glucose and injury severity score (ISS) in children with multiple trauma. METHODS: Charts from all patients 0 to 19 years of age admitted to a children's hospital in 1995 with acute multiple trauma were reviewed. Data collected included initial serum glucose level, heart rate (HR), systolic blood pressure (SBP), Injury Severity Score (ISS), age, gender, location of trauma, and need for intravenous fluids or epinephrine. Data were analyzed using multiple linear regression. RESULTS: A total of 185 charts were reviewed. The mean ISS was 11.3; the mean glucose was 162.8 mg/dL. After adjusting for age, gender, HR, SBP, and administration of epinephrine or fluid bolus, a significant direct relationship between serum glucose and ISS was found (r = 0.52, P < .01). A stronger relationship was found in children less than 2 years old (r = 0.60, P = .04). CONCLUSIONS: A significant direct relationship exists between glucose and ISS in children with multiple trauma. High glucose values may indicate more severe injury, especially in children less than 2 years old.

The relationship of hepatotoxic risk factors and liver histology in methotrexate therapy for juvenile rheumatoid arthritis.

OBJECTIVE: To examine the relationship between hepatotoxic risk factors and liver histopathology in patients with juvenile rheumatoid arthritis (JRA) treated with methotrexate (MTX). STUDY DESIGN: We graded the histology of 33 percutaneous liver biopsy specimens from 25 patients with JRA treated at Children's Hospital Medical Center, Cincinnati, Ohio, using the Roenigk Classification Scale. Stepwise linear and logistic regression analyses were performed to examine the relationship of the Roenigk grade and presence of liver fibrosis of biopsy specimens with potential risk factors. RESULTS: Twenty-seven biopsy specimens (82%) were classified as grade I, 4 (12%) as grade II, and 2 (6%) as grade IIIA; none demonstrated significant fibrosis. The frequency of biochemical abnormalities (P <.001) and body mass index (P =.05) were the only risk factors found to significantly relate to the Roenigk grade. The following factors were not significantly associated with the Roenigk grade: age, gender, disease duration, JRA subtype and course, duration of MTX administration, weekly MTX dose, cumulative dose of MTX, route of MTX administration, use of folic acid supplementation, concurrent use of other medications, and potential hepatotoxic comorbidities. CONCLUSIONS: Serial biochemical abnormalities are significantly associated with Roenigk grade and the presence of liver fibrosis. These findings concur with studies of patients with rheumatoid arthritis, suggesting that guidelines for monitoring MTX hepatotoxicity in rheumatoid arthritis may be applicable to patients with JRA.

Use of methotrexate in children.

Methotrexate continues to be the safest and most efficacious second-line drug for the treatment of JRA. In addition, it is useful in other inflammatory conditions in children. Careful education is necessary, particularly with regard to the importance of laboratory tests and the avoidance of comorbidity such as pregnancy and alcohol-induced liver injury. Health care providers should be comfortable discussing these issues with children and adolescents.

Effect of food palatability on early (cephalic) phase of diet-induced thermogenesis in nonobese and obese man.

OBJECTIVE: To study the effect on the early (cephalic) phase of diet-induced thermogenesis (EDT) of palatable vs unpalatable food, in nonobese and obese man. SUBJECTS: Twenty-four nonobese volunteers and 19 obese clinic patients. DESIGN AND MEASUREMENTS: A palatable, liquid formula meal of Ensure (1048 KJ, 450 ml), and of Ensure made unpalatable by addition of aqueous KCl, were sipped on nonconsecutive mornings. O2 consumption (ml/min) was measured before, and starting 30, 60 and 90 min after beginning the test meal, from which EDT was calculated as KJ/min. RESULTS: Palatability of the test meal significantly increased EDT (palatability effect, P = 0.004) but obesity status per se, did not affect EDT. Nevertheless, the effect of palatability on EDT was dependent on obesity status, being seen only in the nonobese. EDT was significantly greater in the nonobese after the palatable than the unpalatable meal: (mean +/- s.e.m.) 2.45 +/- 0.14 vs 1.83 +/- 0.14; P < 0.0001, but not in the obese: 1.93 +/- 0.28 vs 1.73 +/- 0.20; P < 0.21. Therefore only after the palatable meal was EDT less in the obese compared with the nonobese: P < 0.05. The threshold for the unpleasant taste of added KCI was 31% higher in the obese than the nonobese: 4.2 +/- 0.4 vs 3.2 +/- 0.2 [g KCI]; P < 0.025. CONCLUSIONS: The early (cephalic) phase of dietary thermogenesis (EDT) is significantly increased in the nonobese by palatability, but not in the obese, so that only after a palatable meal is EDT less, or 'deficient,' in the obese compared with the nonobese. Also, the obese have a higher threshold for the unpleasant taste of KCI (in Ensure) than the nonobese.

Coronary artery disease in systemic lupus erythematosus: risk factors, assessment, and prevention.

The 10-year survival rate of patients with systemic lupus erythematosus (SLE) currently is more than 85|X%; the greater longevity permits late complications to emerge. Recent studies have shown an increased incidence of coronary artery disease (CAD), frequently in young adults. CAD currently is among the most common causes of death in patients with SLE who survive longer than 5 years. Multiple risk factors, some specific to SLE, are implicated in premature development of CAD. These include coronary artery vasculitis, hypertension and hyperlipidemia, corticosteroid therapy, and antiphospholipid antibodies, which may result in coronary thrombotic events. Therefore, risk factors for CAD should be actively sought as part of routine care of patients with SLE, and appropriate modification strategies, including medications if necessary, should be employed. Noninvasive cardiac tests should be used early in the evaluation of any symptoms consistent with myocardial ischemia, heart failure, or cardiac arrhythmias.

The long-term effect of methotrexate therapy on the liver in patients with juvenile rheumatoid arthritis.

OBJECTIVE: To determine if the long-term use of methotrexate (MTX) in juvenile rheumatoid arthritis (JRA) is associated with the development of significant liver fibrosis, and to describe the presence of risk factors for liver fibrosis in patients with JRA. METHODS: Needle biopsies of the liver were performed on a cross-section cohort of 14 patients with JRA who had received a total cumulative dose of MTX that was either > 3,000 mg or > 4,000 mg/1.73 m2 of body surface area. Biopsy samples were independently graded according to the Roenigk Classification Scale by 2 pathologists. The presence of risk factors for MTX hepatotoxicity, especially biochemical abnormalities reflective of liver injury and alcohol consumption, were assessed. RESULTS: Thirteen biopsy samples (93%) were classified as grade I, and 1 (7%) as grade II; none demonstrated significant fibrosis. However, histologic abnormalities were found in 13 biopsy samples (93%). Only 2 patients (14%) consumed more than 1 alcoholic drink per month. Thirteen patients (93%) had biochemical abnormalities while being treated with MTX, but only 5 patients (36%) had at least 1 determination in which the aspartate or alanine aminotransferase elevation was > 3 times the upper limit of normal. CONCLUSION: Long-term use of MTX for JRA does not appear to be associated with the development of significant liver fibrosis. Although nearly all patients had minor histologic changes, no significant clinical consequences were apparent. A prospective study of a larger population will more accurately define the incidence of MTX-related liver fibrosis and appropriate monitoring guidelines in JRA.

Vasculitis in systemic lupus erythematosus following intravenous immunoglobulin therapy.

We describe a 6-year-old female patient with systemic lupus erythematosus (SLE) manifested mainly as steroid-dependent thrombocytopenia who developed a vasculitic appearing rash on her palms and soles following treatment with intravenous immunoglobulin (IVIg) (1 gm/kg/infusion x 2, 1 day apart). Vascular occlusion resulting in ischemic gangrene of the fore and midfeet eventually developed, necessitating bilateral amputation. This and other side effects described in SLE indicate that exacerbation of SLE, with the possibility of vasculitis, may occur following IVIg therapy.