Description of the Characteristics of the Nailfold Capillary Structure in Healthy Children: A Multi-Centric Study.

BACKGROUND: Nailfold videocapillaroscopy (NVC) is the primary diagnostic tool for the assessment of microcirculation in the pediatric population. OBJECTIVE: To define and standardize age-specific normal NVC patterns in healthy children and adolescents. METHODS: A cross-sectional observational multicentric study was conducted in 564 participants aged 5-17 years. Dino-Lite CapillaryScope 200 Pro Model MEDL4N Pro was performed at 200× magnification. Quantitative and qualitative NVC parameters were analyzed separately for each age group and divided into 4 groups based on age categories. RESULTS: Of the 564 healthy participants, 54.9% were female. A total of 1184 images and 3384 capillaries were analysed. Positive correlations were observed between age and capillary density (p < 0.001, R = 0.450, CI95% 0.398-0.503). There was also a positive correlation between age and arterial/venous, loop diameter and capillary length, whereas there was a weak negative correlation between intercapillary distance. However, no correlation was found between age and capillary width. In addition, capillary density was significantly lower in 5-7 age group compared to the other patient groups. Arterial limb diameter was lower in 5-7 age group, while venous limb diameter was significantly wider in 15-17 age group compared to the other patient groups. Dilated capillaries (8.7%), capillary tortuosity (14.4%), crossed capillaries (43.1%), micro-haemorrhages (2.7%), avascular area (4.8%) were present in all age groups. Excellent intra- and interobserver ICC values were obtained for all parameters. CONCLUSION: These findings hold potential significance for future studies, aiding in the analysis and differentiation of children suspected of rheumatological diseases with potential microangiopathy.

Macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis on anti-interleukin-1 or -6 therapy.

OBJECTIVES: The aim of this study is to investigate the effect of anti-interleukin (IL)-1/-6 biologics on systemic juvenile idiopathic arthritis (sJIA)-associated macrophage activation syndrome (MAS). METHODS: Demographic, clinical, and laboratory data of patients followed up with a diagnosis of sJIA-associated MAS assessed from sixteen pediatric rheumatology centers across the country. The clinical and laboratory features of MAS developing while on biological drugs were compared with those without this treatment. RESULTS: One hundred and sixty-two patients were included in the study. 45 of the MAS events were detected under the effect of anti-IL-1/-6 biologics, while the patients experiencing the remaining 155 events have not received biological treatment in the last three months. Platelet count [128 (72-232) vs 199 (130-371) 109/l], ferritin level on admission [1107 (676-2050) vs 2863 (1193-9562) ng/ml], C-reactive protein level [15.4 (2.9-56) vs 90 (32-160) mg/l], erythrocyte sedimentation rate [13 (3-36) vs 43.5 (13-77) mm/h] and fever duration [5 (4-7.5) vs 10 (7-14.3) days] were found lower in the group under the impact of anti-IL-1/-6 biologics. Among patients treated with biologics, 26.6% did not meet the published 2016 MAS classification criteria at presentation. The rates of hepatomegaly and splenomegaly were relatively lower in the canakinumab-treated group when compared with those receiving other biologicals or to patients, not on biologicals. CONCLUSION: Anti-IL-1/-6 therapies can mask the clinical and laboratory features of MAS, and proposed guidelines for MAS classification criteria may not be met.

Erratum to `Tuberculosis risk in the biologic era: tuberculin skin test conversion rates in children with rheumatologic diseases` [Turk J Pediatr 2021; 63: 978-985].

This article is corrected. DOI: 10.24953/turkjped.2021.06.005.

Frequency of juvenile idiopathic arthritis and associated uveitis in pediatric rheumatology clinics in Turkey: A retrospective study, JUPITER.

BACKGROUND: Juvenile idiopathic arthritis (JIA), is the most common pediatric rheumatologic disorder with unknown etiology. Currently, no population-based data are available regarding the distribution of categories and frequency of uveitis in patients with JIA in Turkey. The purpose of this study was to evaluate the frequency of JIA-associated uveitis (JIAU) and distribution of JIA categories in a Turkish JIA cohort. METHODS: This was a retrospective study of 500 randomized patients in four pediatric rheumatology clinics in Turkey. RESULTS: Oligoarticular JIA (oJIA) was the most common JIA disease category in this study cohort (38.8%). The frequencies of the other categories were as follows: enthesitis-related arthritis (ERA), 23.2%; rheumatoid factor (RF)-negative polyarthritis, 15.6%; systemic arthritis, 12.2%; juvenile psoriatic arthritis, 5.2%; undifferentiated arthritis, 2.8%; and RF-positive polyarthritis, 2.2%. JIA-associated uveitis was observed in 6.8% of patients at a mean (Standard Deviation, SD) age of 9.1 (3.8) years over a mean JIA disease duration of 4 (1.9) years. Uveitis developed after joint disease, with a mean (SD) duration of 1.8 (1.9) years. Patients with oJIA had the highest rate of uveitis (12.9%) followed by patients with ERA (5.2%) and polyarticular RF-negative disease (3.8%). Compared with persistent oJIA, the extended oJIA category had a > 3-fold higher risk of uveitis (11.3% vs 27.7%; odds ratio, 3.38 [95% Confidence Interval, 1.09-10.4]). The most frequently administered drug after development of uveitis was tumor necrosis factor-alpha inhibitors (38.2%). Five patients (14.7%) had uveitis-related complications that required surgical intervention. CONCLUSIONS: Turkish pediatric patients with JIA experience a lower frequency of oJIA and higher frequency of ERA than their white European counterparts; the occurrence of uveitis is also somewhat lower than expected. Geographic and ethnic factors may affect these differences and need further investigation.

Does Familial Mediterranean Fever Provoke Atherosclerosis in Children? Evaluation of Arterial Stiffness and Serum Endocan Levels.

OBJECTIVES: This study aimed to evaluate the risk for atherosclerosis by using echocardiographic arterial stiffness (AS) parameters and serum endocan levels, as a biomarker of endothelial dysfunction (ED) in children with FMF. METHODS: Seventy-nine children with FMF (12-18 years) and 41 healthy children were included, and clinical features (age at the first attack, age at the time of diagnosis, diagnosis delay time, colchicine dose, biological agent usage, MEFV mutations, and symptoms of attacks) of patients were noted. Arterial stiffness parameters were calculated by using echocardiographic aortic measurements with blood pressure monitoring. Hemogram parameters, acute phase reactants, blood glucose and lipid levels of 12 hours of fasting, and serum endocan levels were evaluated for all participants. RESULTS: There were no statistically significance regarding demographic features, acute phase reactants, and hemogram parameters. Blood glucose and lipid levels were similar, except for HDL (lower in FMF group, p=0.029). Serum endocan levels did not differ in two groups (p=0.906). Only stiffness of descending aorta was lower in FMF group (p=0.028), and the other AS parameters were similar between two groups (p>0.05 for each parameters). CONCLUSION: Good disease control could be preventive for atherosclerosis in children with FMF. On the other hand, screening for cardiovascular diseases is essential, particularly for uncontrolled cases. Distribution of MEFV gene mutations KEY POINTS: • Exaggerated inflammation is the prominent feature of FMF attacks; moreover, it is shown that subclinical inflammation might also continue in attack-free periods. • Chronic inflammation contributes to atherosclerotic process in almost all stages by activating endothelial cells, producing reactive oxygen species, and accelerating foam cell and atherosclerotic plaque formations. • However, the results of this study showed that there was no difference in terms of atherosclerotic markers such as serum endocan levels and arterial stiffness parameters between pediatric FMF patients and healthy peers. • Good disease control in pediatric FMF patients may prevent early atherosclerotic changes during childhood, which then may lead a probable decreased risk of subsequent CVD in adulthood.

Tuberculosis risk in the biologic era: tuberculin skin test conversion rates in children with rheumatologic diseases.

BACKGROUND: The widespread use of biological treatments has increased the frequency of opportunistic infections such as tuberculosis (TB). The primary objective of our study was to determine the rate of tuberculin skin test (TST) conversion during biological therapy. The secondary objective was to monitor the side effects related to isoniazid (INH) prophylaxis, in the selected subgroup. METHODS: Children with rheumatologic diseases receiving treatment with tumor necrosis factor-alpha (TNF-α) inhibitors, and tocilizumab and canakinumab were included in the study. If baseline screening was negative, TST was performed annually after initiation of biologic therapy. TST conversion was accepted as an increase of at least 6 mm and becoming positive or an increase of 10 mm or more, even in the absence of positivity. RESULTS: 121 patients (female n: 63, 52%) were included in the study. The mean follow-up period was 26.10±14.8 months. 85 of the patients were using TNF-α inhibitors and 18 tocilizumab, and 18 canakinumab. Forty patients had positive TST before biological agents and received chemoprophylaxis with INH. The rate of TST conversion among the 3 biological agents was not statistically significant (20.4% of TNF-α inhibitors, 25% of canakinumab and 33.3% of tocilizumab users). All patients with LTBI received INH prophylaxis, and none of them had active TB. CONCLUSIONS: There was no statistically significant difference among the three biological agents, regarding the seroconversion rates. Patients receiving tocilizumab and canakinumab should also be screened for TB during follow-up. INH related side effects are rare.

Obesity is associated with severe clinical course in children with Henoch-Schonlein purpura.

BACKGROUND: We aimed to evaluate the role of obesity on the clinical course and response to treatment in patients with Henoch-Schonlein purpura (HSP). METHODS: Data charts of children with HSP followed in a tertiary hospital between 2000 and 2018 were reviewed retrospectively. Persistent purpura was defined as skin involvement persisting for ≥ 30 days. Mild nephropathy was defined as the presence of microscopical hematuria and/or non-nephrotic proteinuria, while severe nephropathy as nephrotic proteinuria, nephritic syndrome, and/or kidney insufficiency. Obese and non-obese patients were compared for demographic, clinical, and laboratory parameters. RESULTS: There were 199 patients (M/F, 104/95; median (IQR) presenting age 7.1 (5.0-9.2) years; follow-up period 17.5 (6-50) months). Obese patients (n = 35 (17.6%)) had significantly higher rate of persistent purpura (46% vs 21%), severe renal involvement (58% vs 31%), high-grade renal histopathological lesions (83% vs 39%), hypertension (29% vs 9%), and increased erythrocyte sedimentation rate (79% vs 56%). Obese patients also showed delayed improvement of cutaneous (25 vs 14 days), articular (12.5 vs 10.0 days), and kidney (280 vs 57 days) symptoms. Obese children used steroids for significantly longer period of time (236 vs 40 days). Furthermore, need for immunosuppressive medications were higher in obese patients (40% vs 9%). CONCLUSIONS: Obese children with HSP had higher erythrocyte sedimentation rate, hypertension, and severe renal involvement; showed delayed improvement of skin, joint, and kidney findings; and need more immunosuppressive medications and a longer period of steroid treatment. These findings may be associated with the effect of adipose tissue on inflammation.

Risk factors of intravenous immunoglobulin resistance and coronary arterial lesions in Turkish children with Kawasaki disease.

Kawasaki disease (KD) is the most common cause of childhood coronary artery disease. The incidence of coronary artery lesions (CALs) has declined with the routine use of intravenous immunoglobulin (IVIG) treatment, but there is still considerable risk for resistance to IVIG treatment and development of CALs. The present study was aimed to determine the risk factors in Turkish children with IVIG resistant KD and coronary artery involvement. Clinical, laboratory and echocardiographic data were retrospectively analyzed in 94 Kawasaki patients. IVIG resistant and responsive groups were compared. The IVIG resistant group had a higher rate of CALs compared to the IVIG responsive group (p < 0.05). Duration of fever ≥ 9.5 days, C-reactive protein (CRP) ≥ 88 mg/L and Neutrophil/lymphocyte ratio (NLR) ≥1.69 were the best cutoff values for predicting IVIG resistance before treatment. The criteria for at least two of these three predictors were considered to be statistically significant risk factors for detecting IVIG resistance in KD before treatment (76.47% sensitivity, 71.05% specificity and 95% CI were 50.1-93.19% and 59.51-80.89%, respectively). Based on the clinical and laboratory features, we established a new risk-scoring system for predicting IVIG resistance in a cohort of Turkish children with KD. This may be useful for choosing optimal treatment for KD to prevent coronary artery involvement.

Protective Effect of Acetyl-L-Carnitine Against Doxorubicin-induced Cardiotoxicity in Wistar Albino Rats.

BACKGROUND AND AIMS: Anthracyclines are one of the most preferred agents in practical pediatric oncology despite their dose-dependent cardiotoxic effects. The aim of this study was to investigate whether or not acetyl-L-carnitine (ALCAR) has protective effects on doxorubicin (DOX)-induced cardiotoxicity. METHODS: Wistar rats were divided into four groups; control, DOX, ALCAR and ALCAR+DOX. Rats in the first group were given saline on study days, whereas those in the second group were given a single dose of DOX on the 5th day and saline on the other days. Rats in the third group were given ALCAR and those in the fourth group were given ALCAR on study days but also given only a single dose of DOX on the fifth day of the study. Ejection fractions (EF) were measured by echocardiography before and after drug administration. Heart tissues were evaluated by light and electron microscopy. Apoptotic cells were determined with TUNEL and caspase-3 staining. RESULTS: DOX significantly decreased the EF values, whereas ALCAR did not. Cardiac functions were higher in the ALCAR+DOX group when compared to the DOX group. DOX administration caused a cardiac injury not only functionally, but also structurally, whereas ALCAR prevented it. CONCLUSIONS: ALCAR has a capacity of preventing DOX-induced cardiac injury at both functional and structural levels.