Nilgün Çakar

Background: Ambulatory blood pressure monitoring (ABPM) offers a comprehensive assessment of mean blood pressure (BP), circadian patterns, and out-of-office hypertension phenotypes. We evaluated the association of ABPM parameters with left ventricular hypertrophy (LVH) and hypertensive retinopathy (HRP) in children with hypertension. Methods: This retrospective analysis included 269 children who underwent ABPM at a tertiary care facility. Multivariable logistic regression was used to evaluate associations between BP Z scores and target organ damage (TOD), adjusting for age, sex, and body mass index standard deviation score. Machine learning techniques (logistic regression, random forest, and multilayer perceptron) were also evaluated using 10-fold cross-validation across exploratory combinations of the 90th or 95th percentiles and BP-load thresholds of 25% or 50%. Results: LVH was detected in 45/247 patients (18%) and HRP was observed in 22/240 patients (9%). The 24 h systolic BP Z score was independently associated with LVH (adjusted OR 1.44; 95% CI 1.16–1.80; p = 0.001). Cohort-derived systolic Z-score thresholds for LVH were 1.31 for 24 h systolic BP and 1.47 for nighttime systolic BP, corresponding to approximately the 90.6th and 93rd percentiles, respectively. No variable evaluated was independently associated with retinopathy. Logistic regression using the 90th percentile/25% load dataset showed the highest performance among the evaluated classifiers, but discrimination was limited (ROC area 0.603; MCC 0.041). Conclusions: Higher ambulatory systolic BP was independently associated with LVH but not with clinically detected hypertensive retinopathy. ABPM values at or above the 90th percentile and a systolic load of ≥25% may help identify children at increased risk of TOD, although these thresholds remain exploratory and require prospective external validation.

Objective: Fragile nature of the patients in the pediatric intensive care unit (PICU) can lead to severe electrolyte imbalances with life-threatening consequences. Dysnatremia is one of the most common disorders in this setting. This study aimed to investigate the causes, severity and concomitant diseases of dysnatremia in the PICU and factors affecting mortality in these patients. Material and Methods: This study was carried out between March 2013 and October 2014 in Ankara Children’s Hematology Oncology Training and Research Hospital. The patients admitted to PICU between 1 month and 18 years of age were included in the study. Hypernatremic patients were grouped as mild (145>Na≥160 mEq/L) and severe (Na>160 mEq/L); and hyponatremic patients were also grouped as mild (120≤Na <135 mEq/L) and severe (Na<120 mEq/L). Results: Out of the 101 dysnatremic patients (57 male/ 44 female) with a mean age of 79±71 months, 60% had hypernatremia, 40% had hyponatremia. Eighty-nine (88.1%) of the dysnatremic patients had comorbid chronic diseases, with central nervous system (CNS) disorders as the leading cause. The overall mortality rate of PICU was 17%, and the mortality rate of dysnatremic patients was 53%. The presence of concomitant chronic diseases was associated with increased mortality [OR, 3.84 (CI %95, 0.9-15.1)]. Mortality was more common in patients with severe and uncorrected hypernatremia, respectively (p=0.005, p=0.010). Conclusion: Dysnatremia is frequent in PICU. The presence of chronic comorbidities, severe and uncorrected dysnatremia increases the risk of mortality in the PICU. Awareness of this risk is important to improve survival in these vulnerable population.

Background: Familial Mediterranean fever (FMF) is a monogenic autoinflammatory disease, and colchicine is the mainstay of treatment. Approximately 5%–10% of patients may respond inadequately to colchicine, and anti–interleukin-1 (anti-IL-1) agents are important treatment options in these patients. The aim of this study was to see whether there is any factor associated with the withdrawal of these anti-IL-1 agents and to investigate the characteristics of colchicine-resistant FMF patients who needed biological therapy. Methods: Demographic, clinical characteristics, and disease severity of patients, at 2 referral centers, between 2012 and 2022, in whom anti-IL-1 treatment was continued and discontinued, were compared in this study. The international severity scoring system for FMF (ISSF) was used for disease severity assessment. Results: In 64 colchicine-resistant FMF patients, the median (interquartile range) duration of biological treatment was 39 (45) months. Treatment of 26 patients (40.6%) was started with anakinra and 38 (59.4%) with canakinumab. During follow-up, anti-IL-1 treatment was discontinued in 23 patients (35.9%). High ISSF scores before biological treatment, presence of exertional leg pain, subclinical inflammation, and comorbidities were found to be statistically more frequent in the group whose biological therapy could not be discontinued (p = 0.009, p = 0.006, p = 0.026, p = 0.001, respectively). Conclusions: Low ISSF scores before biological treatment with no accompanying exertional leg pain, subclinical inflammation, and comorbidities may be stated as an associated factors in terms of the discontinuation of biological agents in colchicine-resistant pediatric FMF patients.

To evaluate adverse events (AEs) in pediatric patients with rheumatologic diseases being treated with approved or off-label biologic agents (BAs). This observational, retrospective, multicenter study was conducted from 2010 to 2022 in patients under 18 years of age with rheumatic diseases who were receiving interleukin-1 antibodies (Anti-IL1), interleukin-6 antibodies (Anti-IL6), and tumor necrosis factor alpha inhibitors (anti-TNF). Efficacy, AEs, and timing of AEs were collected from electronic medical records. Three hundred and fifteen BAs were prescribed to 237 patients. Fifty AEs occurred in 44 patients (18.6%). Anti-TNF exposure was present in 8 (72.2%) of 11 patients with latent tuberculosis (TB) and in all 7 patients with herpes infections. Four of 6 patients (66.7%) with recurrent upper respiratory tract infections and 7 of 8 patients (87.5%) with local skin reactions were on Anti-IL1. The cutoff value for latent TB development was determined as 23.5 months by ROC analysis (AUC: 0.684 ± 0.072, p = 0.038, 95% CI: 0.54-0.82). In patients who used BA for 23.5 months or more, the risk of latent TB was 5.94-fold (p = 0.024, 95% CI: 1.26-27.97). Drug rash with eosinophilia and systemic symptoms (DRESS) occurred in 2 patients on anakinra, and anaphylaxis occurred in 1 patient on anti-IL6. There were no cases of malignancy or death in any patient. The physician should be vigilant for latent TB in patients exposed to BA for more than 2 years. While local skin reactions are more prevalent in patients receiving anti-IL1, severe skin reactions such as DRESS may also occur.

Background: Children’s urinary system stones may develop from environmental, metabolic, anatomical, and other causes. Our objective is to determine the recurrence and prognosis, demographic, clinical, and etiological characteristics of children with urolithiasis. Methods: Medical records of patients were evaluated retrospectively. Patients’ demographic data and medical history, serum/urine biochemical and metabolic analysis, blood gas analysis, stone analysis, imaging findings, and medical/surgical treatments were recorded. Results: The study included 364 patients (male 187). Median age at diagnosis was 2.83 (IQR 0.83–8.08) years. The most common complaints were urinary tract infection (23%) and urine discoloration (12%). Sixty-two percent had a family history of stone disease. At least one metabolic disorder was found in 120 (88%) of 137 patients having all metabolic analyses: hypercalciuria was found in 45%, hypocitraturia in 39%, and hyperoxaluria in 37%. Anatomical abnormalities were detected in 18% of patients. Of 58 stones analyzed, 65.5% were calcium and 20.6% were cystine stones. Stone recurrence rate was 15% (55/364). Older age (> 5 years), family history of stone disease, stone size (≥ 5 mm), and urinary system anatomical abnormalities were significantly associated with stone recurrence (p = 0.027, p = 0.031, p < 0.001, and p < 0.001, respectively). In adjusted logistic regression analysis, stone size ≥ 5 mm (OR 4.85, 95% CI 2.53–9.3), presence of urinary system anatomical abnormalities (OR 2.89, 95% CI 1.44–5.78), and family history of stone disease (OR 2.41, 95% CI 1.19–4.86) had increased recurrence rate. Conclusions: All children with urolithiasis should be evaluated for factors affecting stone recurrence. Children at higher risk of recurrence need to be followed carefully. Graphical

This study included patients followed up for primary renal tubular acidosis (RTA) between 1991 and 2012. Clinical characteristics at presentation, physical examination findings, laboratory test results, and treatments were recorded. The patients’ laboratory results, drug doses, height, and weight were recorded every 3 months for the first year of follow-up. Standard deviation scores (Z-scores) of height and weight for age were determined and the patients’ growth rates were evaluated. Of 50 patients followed up for primary RTA, 31 (62%) had distal RTA and 19 (38%) had proximal RTA. The median age at diagnosis was 3 months (range, 1-174 months) for patients with distal RTA and 10 months (range, 2-33 months) for patients with proximal RTA. The median follow-up times in these two groups were 96 months (range, 6-204 months) and 89 months (range, 6-180 months), respectively. Family history of RTA was more common among patients with distal RTA than those with proximal RTA (p=0.013). Nephrocalcinosis and deafness were detected more frequently in the distal RTA group (p=0.001), while ocular pathologies were more common in the proximal RTA group (p<0.001). In patients with distal RTA, older age at diagnosis was associated with lower weight and height Z-scores (p<0.05). Early diagnosis had a positive effect on the growth of patients with primary RTA.

Objective: Familial Mediterranean fever (FMF) is the most prevalent hereditary autoinflammatory disease among children. Abdominal pain and various gastrointestinal system (GIS) manifestations may arise directly from FMF or concomitantly with FMF. This study aimed to evaluate GIS complaints and findings other than classic peritonitis attacks in patients with FMF and to interpret concomitant GIS and hepatic disorders in these patients. Methods: The medical and genetic findings of patients with FMF who attended our clinic between December 2011 and December 2021 were reviewed. Gastrointestinal system symptoms, liver function tests, abdominal images, and endoscopic and histopathological data were extracted from medical records. Results: A total of 576 pediatric patients (female, 52.3%) diagnosed with FMF were included. Among them, almost one-fifth displayed GIS complaints, such as abdominal pain, defecation problems, and dyspepsia, distinct from typical FMF attacks. High serum aminotransferase levels were detected in 18.4% of the patients, with viral infections being the most common cause of moderate/severe hypertransaminasemia. In addition, during follow-up, 26.9% of them were referred to the pediatric gastroenterology department. At least 1 gastroenterological and hepatobiliary disorder was detected in 17.5% of the patients because of organic and functional GIS disorders or hepatobiliary disorders, such as gastroesophageal reflux disease, esophagitis, functional dyspepsia, and inflammatory bowel diseases. Conclusion: Various GIS and hepatic disorders can be encountered in children with FMF. The spectrum of these complaints and pathologies can range from frequently observed health problems to more severe diseases.

Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease. Recurrent fever, serositis and arthritis are common findings of the disease. In addition, musculoskeletal complaints such as exertional leg pain can be overlooked, although they are common and affect patients' quality of life. The aim of this study was to evaluate the frequency of exertional leg pain in pediatric FMF patients and to analyze the association of this finding with other characteristics of FMF. The files of FMF patients were retrospectively evaluated. The clinical characteristics and disease severity of the patients with exertional leg pain were compared with the patients without exertional leg pain. International severity scoring system for FMF (ISSF) and Mor severity score were used for assessment. The study included 541 FMF patients (287 females), 149 (27.5%) with exertional leg pain. The median colchicine dosage was significantly higher in patients with exertional leg pain (p = 0.02), arthritis (p = 0.001) and arthralgia (p˂0.001) were encountered more frequently in the attacks of these patients. The median disease severity scores calculated by both Mor severity scale and ISSF were significantly higher in patients with exertional leg pain compared to those without (p˂0.001). In the group of patients with exertional leg pain the M694V mutation, either in 1 allele or in 2 alleles, was found to be significantly more common (p = 0.006 and p˂0.001, respectively). Exertional leg pain in pediatric FMF patients is the component of moderate-to-severe disease course, and this may be considerably associated with the presence of M694V mutation.

Objective: Erysipelas-like erythema is the pathognomonic skin manifestation of familial Mediterranean fever although not frequently seen in the pediatric population. This study aims to describe the differences between patients presenting with and without erysipelas-like erythema and to examine the relation of erysipelas-like erythema with subclinical inflammation in a large pediatric cohort of familial Mediterranean fever patients. Materials and Methods: This retrospective study from a single pediatric rheumatology referral center included familial Mediterranean fever patients with a follow-up for at least 6 months in the last 5 years. Patients were grouped according to the presence of erysipelas-like erythema and subclinical inflammation. Results: Among 515 patients with familial Mediterranean fever, 35 patients (6.8%) were found to present with erysipelas-like erythema, and the earliest age for erysipelas-like erythema was 2.9 years. All erysipelas-like erythema lesions were defined on lower extremities with concurrent arthritis in 21 patients (60.0%). Compared to other patients in the cohort, patients presented with erysipelas-like erythema had significantly higher frequencies of acute arthritis, subclinical inflammation, and biallelic exon 10 mutations, and they used significantly higher doses of colchicine at the latest visits (all P ≤ .002). Patients with subclinical inflammation more frequently presented with erysipelas-like erythema compared to others without subclinical inflammation (21.7% vs. 2.9%, P < .001). Conclusion: Erysipelas-like erythema is an uncommon but important finding that can be a sign of severe disease course and subclinical inflammation in the pediatric population with familial Mediterranean fever. Cite this article as: Avar-Aydın PÖ, Özçakar ZB, Aydın F, Karakaş HD, Çakar N, Yalçınkaya F. Erysipelas-like erythema: A manifestation of severe disease phenotype in pediatric patients with familial mediterranean fever. Turk Arch Pediatr. 2022;57(6):599-602.