Evaluation of plasma carnitine status in patients diagnosed with juvenile idiopathic arthritis.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood and manifests mainly as autoinflammation of the joints and other tissues. Several treatment options such as nonsteroidal antiinflammatory drugs, methotrexate, and intra-articular steroids are widely used to relieve and improve this inflammation. Secondary carnitine deficiency can be detected in chronic diseases by either renal loss or increased demand. While carnitine status can be associated with several conditions, in the present study our aim is to determine the levels of free carnitine and acyl-carnitine in Turkish JIA patients. METHODS: One hundred and fourteen patients diagnosed with juvenile idiopathic arthritis and 50 healthy individuals who served as the control group were included in the study. A fasting blood sample was collected from the children in both groups to determine free carnitine and acylcarnitine ester by quadripole electrospray tandem mass spectrometry (ESI-MS/ MS). RESULTS: Screening of acyl-carnitine profile revealed free carnitine, C14, C14:2, C16, C16-OH, and C18 carnitine levels were higher (p < 0.0001, p < 0.0001, p < 0.001, p < 0.001, and p = 0.011, respectively), while C2, C3, C4, C6, C8, C10, C10:1, C10:2, C3DC, C4DC, C5DC, C4-OH, and C18:1-OH carnitine levels were lower (p < 0.0001) in JIA patients in comparison to the control group. Total acyl-carnitine levels (p < 0.001) and acyl-carnitine to free carnitine ratio (p < 0.001) were also lower in JIA patients than the control group. Free carnitine levels were significantly higher (48.05 ± 13.36 µmol/L) in patients under antiinflammatory drug therapy than those who did not receive any treatment (43.18 ± 7.96 µmol/L) (p = 0.004). DISCUSSION: In the present study we were not able to define secondary carnitine deficiency in JIA patients, although free carnitine and acyl-carnitine variations were detected in JIA patients. In conclusion, routine carnitine supplementation is not recommended in all patients with JIA.

Consensus-based recommendations for the management of juvenile localised scleroderma.

In 2012, a European initiative called Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) was launched to optimise and disseminate diagnostic and management regimens in Europe for children and young adults with rheumatic diseases. Juvenile localised scleroderma (JLS) is a rare disease within the group of paediatric rheumatic diseases (PRD) and can lead to significant morbidity. Evidence-based guidelines are sparse and management is mostly based on physicians' experience. This study aims to provide recommendations for assessment and treatment of JLS. Recommendations were developed by an evidence-informed consensus process using the European League Against Rheumatism standard operating procedures. A committee was formed, mainly from Europe, and consisted of 15 experienced paediatric rheumatologists and two young fellows. Recommendations derived from a validated systematic literature review were evaluated by an online survey and subsequently discussed at two consensus meetings using a nominal group technique. Recommendations were accepted if ≥80% agreement was reached. In total, 1 overarching principle, 10 recommendations on assessment and 6 recommendations on therapy were accepted with ≥80% agreement among experts. Topics covered include assessment of skin and extracutaneous involvement and suggested treatment pathways. The SHARE initiative aims to identify best practices for treatment of patients suffering from PRDs. Within this remit, recommendations for the assessment and treatment of JLS have been formulated by an evidence-informed consensus process to produce a standard of care for patients with JLS throughout Europe.

Juvenile Idiopathic Arthritis.

Juvenile idiopathic arthritis is the most common chronic rheumatic disease of unknown aetiology in childhood and predominantly presents with peripheral arthritis. The disease is divided into several subgroups, according to demographic characteristics, clinical features, treatment modalities and disease prognosis. Systemic juvenile idiopathic arthritis, which is one of the most frequent disease subtypes, is characterized by recurrent fever and rash. Oligoarticular juvenile idiopathic arthritis, common among young female patients, is usually accompanied by anti-nuclear antibodie positivity and anterior uveitis. Seropositive polyarticular juvenile idiopathic arthritis, an analogue of adult rheumatoid arthritis, is seen in less than 10% of paediatric patients. Seronegative polyarticular juvenile idiopathic arthritis, an entity more specific for childhood, appears with widespread large- and small-joint involvement. Enthesitis-related arthritis is a separate disease subtype, characterized by enthesitis and asymmetric lower-extremity arthritis. This disease subtype represents the childhood form of adult spondyloarthropathies, with human leukocyte antigen-B27 positivity and uveitis but commonly without axial skeleton involvement. Juvenile psoriatic arthritis is characterized by a psoriatic rash, accompanied by arthritis, nail pitting and dactylitis. Disease complications can vary from growth retardation and osteoporosis secondary to treatment and disease activity, to life-threatening macrophage activation syndrome with multi-organ insufficiency. With the advent of new therapeutics over the past 15 years, there has been a marked improvement in juvenile idiopathic arthritis treatment and long-term outcome, without any sequelae. The treatment of juvenile idiopathic arthritis patients involves teamwork, including an experienced paediatric rheumatologist, an ophthalmologist, an orthopaedist, a paediatric psychiatrist and a physiotherapist. The primary goals of treatment are to eliminate active disease, to normalize joint function, to preserve normal growth and to prevent long-term joint damage. Timely and aggressive treatment is important to provide early disease control. The first-line treatment includes disease-modifying anti-rheumatic drugs (methotrexate, sulphasalazine, leflunomide) in combination with corticosteroids, used in different dosages and routes (oral, intravenous, intra-articular). Intra-articular application of steroids seems to be an effective treatment modality, especially in monoarthritis. Biological agents should be added in the treatment of unresponsive patients. Anti-tumour necrosis factor agents (etanercept, infliximab, adalimumab), anti-interleukin-1 agents (anakinra, canakinumab), anti- interleukin-6 agents (tocilizumab) and T-cell regulatory agents (abatacept) have been shown to be safe and effective in childhood patients. Recent studies reported sustained reduction in joint damage with even complete clinical improvement in paediatric patients, compared to previous data.

Vitamin D levels in children with familial Mediterranean fever.

BACKGROUND: This study aimed to determine whether vitamin D deficiency is more common in children with familial Mediterranean fever (FMF) than in healthy individuals. METHODS: The study group consisted of 100 patients diagnosed with FMF and 50 healthy children. Serum baseline 25-hydroxyvitamin D levels and other related parameters were evaluated. RESULTS: The mean (standard deviation [SD]) vitamin D levels in patients with FMF and healthy controls were 24.78 (8.35) and 28.70 (11.70) ng/mL, respectively. Patients with FMF had significantly decreased vitamin D levels compared with those in healthy controls (P = 0.039). Vitamin D levels were similar in patients with FMF with different MEFV mutations (P = 0.633). Age was significantly correlated with vitamin D levels (r = -0.235, P = 0.019). In addition, a negative correlation between parathyroid hormone and vitamin D levels was detected (rs = -0.382, P < 0.0001). CONCLUSION: This study demonstrated that vitamin D levels are lower in children with FMF than in healthy controls. We speculate that vitamin D levels should be carefully examined, and nutritional supplementation may be required in patients with FMF. Further studies with larger patient populations are needed to confirm the frequency of vitamin D deficiency in patients with FMF.

Severe digital necrosis in a 4-year-old boy: primary Raynaud's or jellyfish sting.

Raynaud's phenomena is a common disorder which may be primary or secondary to some connective tissue disorders such as systemic sclerosis and systemic lupus erythematosus. Jellyfish sting is a rare but life-threatening cause of Raynaud's phenomena. Digital gangrene is reported in 3% of children with secondary Raynaud's phenomena but does not occur in children with primary Raynaud's phenomena. We report a case of a 4-year-old boy who initially presented with episodes of pain and bluish to blackish discolouration and necrosis affecting the fingers on both hands after a jellyfish sting without any sign of connective tissue disorder.

Traditional and "new" cardiovascular risk markers and factors in pediatric dialysis patients.

Cardiovascular disease (CVD) is the principal cause of mortality in patients with end-stage renal disease (ESRD). The aim of this study was to analyze carotid intima-media thickness (cIMT), endothelium-dependent dilatation (EDD), and left ventricular mass index (LVMI) as the cardiovascular risk markers and to investigate the independent risk factors of these markers in pediatric dialysis patients. This study included 39 children and adolescents undergoing dialysis (15 hemodialysis and 24 peritoneal dialysis) and 15 age- and gender-matched healthy subjects. The cIMT and EDD were assessed by high-resolution ultrasound, and LVMI was calculated from standard echocardiographic measurements. Compared with control subjects, cIMT standard deviation scores (SDS), LVMI, total homocysteine (tHcy), and high-sensitivity C-reactive protein (hs-CRP) values were significantly higher in patients, but EDD values did not differ. The mean hs-CRP level was significantly higher in hemodialysis (HD) patients than in peritoneal dialysis (PD) patients. The cIMT-SDS and LVMI were associated with several variables in univariate analysis. Stepwise linear regression analysis, indexed SBP (p = 0.017), and hemoglobin (p = 0.001) turned out to be independent variables for predicting LVMI, and a significant predictor of cIMT was indexed diastolic blood pressure (DBP) (p = 0.035). The causes of atherosclerosis and left ventricular hypertrophy are multifactorial in children and adolescents with ESRD. Better management of hypertension and anemia may be priorities for preventing or improving CVD in these patients.

Coronary artery calcifications in children with end-stage renal disease.

Coronary artery calcification (CAC) is common in adults with end-stage renal disease (ESRD), but little is known about the prevalence and the extent of it in children. We used multidetector spiral computed tomography (MDCT), echocardiography, and carotid and brachial high-resolution ultrasonography to screen for the presence and predisposing factors of CAC in 53 children with ESRD [15 hemodialysis (HD) patients, 24 peritoneal dialysis (PD) patients, and 14 renal transplant (rTx) recipients]. CAC was present in 15% of patients (three HD patients, three PD patients, and two rTx). The mean age of the patients with CAC was 16.4 years (range: 11.0-21.2 years), and their median CAC score was 101.3, ranging from 8.5 to 4,322 according to the Agatston method. The patients with CAC had longer duration of total dialysis (P=0.005), had higher time-integrated serum phosphorus (P<0.001), calcium-phosphate (CaxP) product (P=0.012), intact parathyroid hormone (P=0.010), vitamin B(12) levels (P=0.010), the amount of cumulative calcium-containing oral phosphate binders (OBPs) (P<0.001), and calcitriol intake (P<0.001), and had lower serum hemoglobin level (P=0.014). Interventricular septum systolic thickness (P=0.033) was significantly higher, relative wall thickness (P=0.062) tended to be higher, and flow-mediated endothelium-dependent dilatations (P=0.071) were lower without reaching statistically significant levels in those with CAC. A stepwise logistic regression analysis revealed that serum phosphorus (P=0.018) and the cumulative exposure to calcium-containing OPBs (P=0.016) were the most significant independent predictors in the development of CAC. These results indicate that even adolescents and children with ESRD may have coronary calcifications. We concluded that impaired divalent ion metabolism is the main factor in the formation of CAC in this age group.

Carnitine supplementation improves apolipoprotein B levels in pediatric peritoneal dialysis patients.

There have been conflicting reports concerning the effect of carnitine supplementation on lipid metabolism in patients on peritoneal dialysis (PD). We investigated several parameters of lipid metabolism in pediatric PD patients supplemented with carnitine. The study included 20 patients receiving PD (treatment group) aged 2-18 years and a matched healthy control group. In the treatment group, baseline triglyceride, total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and apolipoprotein B levels were higher than in the control group. High-density lipoprotein cholesterol, free fatty acid, phospholipids, and apolipoprotein A-I levels were not different from those in the control group. The baseline plasma free carnitine level was lower and acyl-carnitine level was higher in the treatment group. No difference was found between the groups with respect to plasma total carnitine levels. Oral l-carnitine supplementation (50 mg/kg per day for 30 days) led to a significant decrease (from a baseline value of 146.6+/-51.8 mg/dl to 63.6+/-22.2 mg/dl, P<0.001) in apolipoprotein B levels, and no significant change in the other lipid parameters of the treatment group. Oral l-carnitine supplementation does not ameliorate the lipid profile in pediatric PD patients, but it causes a significant decrease in apolipoprotein B levels. Hence, carnitine supplementation may be recommended for decreasing apolipoprotein B levels in this patient population.