A 7-year-old boy with scurvy owing to coeliac disease.

ABBREVIATIONS: ESR: erythrocyte sedimentation rate; Hb: haemoglobin; HSP: Henoch-Schönlein purpura; WCC: white-cell count.

Using Antinuclear Antibody Testing in Pediatric Rheumatology.

The antinuclear antibody (ANA) test is frequently used for the identification of patients who are at a high risk of developing autoimmune rheumatological diseases. The aim of this study is to evaluate the final diagnoses of patients applied to the pediatric rheumatology outpatient clinic with a positive ANA test result. In this study, the medical records of 283 children who had ANA positivity between January 2010 and January 2022 were evaluated retrospectively. All patients were younger than 18 years of age at diagnosis and were followed up in the pediatric rheumatology department for at least 6 months. The majority of the patients were females (69%), and the mean age was 9.9 ± 4.7 years. 94% of the ANA tests were requested in pediatric rheumatology outpatient clinics, and 6% in general pediatrics and other outpatient clinics. Arthritis was the most common reason for ANA testing (41.7%). Of the patients who had ANA positivity, 37% were diagnosed with juvenile idiopathic arthritis (JIA), 15% with connective tissue diseases, 10% with autoinflammatory disease, and 7% with vasculitides. Positivity at 1/320 and 1/640 titers were more common in the patients diagnosed with autoimmune connective tissue diseases or JIA compared to the patients without these diagnoses (P = .009 and P = .013, respectively). The ANA test should be judiciously requested by pediatric rheumatologists, especially in suspected cases of autoimmune rheumatic disorders and JIA patients to aid in classification. Indiscriminate use of the ANA test for screening may potentially misguide clinicians.

Thymic carcinoma presenting with overlap polyarthritis and myositis: A rare paraneoplastic syndrome in childhood.

Thymic tumors are very rare neoplasms in children and account for less than 1% of mediastinal tumors in pediatric patients. One-third of the pediatric patients present with symptoms related to the compression of the tumor mass on the surrounding anatomic structures, and paraneoplastic syndromes such as myasthenia gravis, pure red cell aplasia, acquired hypogammaglobulinemia, and connective tissue disorders, which rarely occur in children with thymic tumors. Herein, we report a case of thymic carcinoma mimicking the symptoms of a connective tissue disease with symmetrical polyarthritis accompanying myositis, fever, weight loss, and malaise in a 15-year-old male patient. To our knowledge, this is the first case pediatric thymic carcinoma accompany with severe polyarthritis and myopathy, thus we have reviewed the current literature regarding the cases of thymic malignancies coexisting with paraneoplastic syndromes in children.

How Safe Are Biological Agents in Pediatric Rheumatology?

OBJECTIVE: Biologic therapy has changed the prognosis of patients with rheumatologic disease. Despite all benefits of the biological agents, adverse events may occur due to their long-term use. The aim of this study is to analyze the adverse events observed in pediatric patients who received biological treatment. MATERIALS AND METHODS: This retrospective observational cohort study was conducted between January 2010 and January 2022. File records of 139 patients used biological agents for rheumatologic diseases in a pediatric rheumatology clinic were evaluated. Diagnosis, received treatment, the rationale for stopping treatment, requirement of tuberculosis prophylaxis, presence of an adverse event, and results were recorded. RESULTS: The most used biological therapy was etanercept (41.7%). Anakinra, adalimumab, canakinumab were used in 30.9%, 27.3%, 23.7% of patients, and the others in less than 10%. Totally 491 adverse events (97.9/100 patient-years) were encountered during the duration of biological treatment. The most often adverse event was recurrent upper respiratory tract infection in the patients (31.9/100 patient-years). Elevated aminotransferase levels (10.4/100 patient-years), abdominal pain (7/100 patient-years), and headache (5.2/100 patient-years) were among the other common side effects. Isoniazid (INH) prophylaxis was needed before biological treatment in 20.9% of the patients. Tuberculosis developed in none of the patients followed-up for latent tuberculosis, however, it developed in a patient while receiving etanercept due to noncompliance with his scheduled outpatient visits during etanercept treatment. CONCLUSION: The most commonly used biological treatments were TNFi and IL-antagonists, and the majority of side effects were infections and laboratory abnormalities. Although the rate of serious adverse events is quite low, close follow-up of patients receiving biological therapy is very important.

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.

Pediatric kidney care experience after the 2023 Turkey/Syria earthquake.

BACKGROUND/AIMS: Two earthquakes on February 6th, 2023 destroyed ten cities in Türkiye. We report our experience with pediatric victims during these catastrophes, with a focus on crush syndrome related-acute kidney injury (Crush-AKI) and death. METHOD: A web-based software was prepared. Patient demographics, time under rubble (TUR), admission laboratory data, dialysis, and kidney and overall outcomes were asked. RESULTS: 903 injured children (median age: 11.62 years) were evaluated. Mean TUR was 13 h (Interquartile range-IQR: 32.5), max 240 h). 31 of 32 patients with a TUR of >120 h survived. The patient who rescued after ten days survived.Two-thirds of the patients were given 50 mEq/L sodium-bicarbonate in 0.45% sodium-chloride solution on admission day. 58% of patients were given intravenous fluid (IVF) at a volume of 2000-3000 mL/m2 body surface area (BSA), 40% of 3000-4000 mL/m2 BSA, and only 2% of >4000 mL/m2 BSA. 425 patients had surgeries, 48 suffered from major bleeding. Amputations were recorded in 96 patients. Eighty-two and 66 patients required ventilator and inotropic support, respectively.Crush-AKI developed in 314 patients (36% of all patients). 189 patients were dialyzed. Age > 15 years, creatine phosphokinase (CK)≥20 950 U/L, TUR≥10 h, and the first-day IVF volume < 3000-4000 mL/m2 BSA were associated with Crush-AKI development. 22 deaths were recorded, 20 of 22 occurred in patients with Crush-AKI and within the first 4 days of admission. All patients admitted after 7 days survived. CONCLUSIONS: This is the most extensive pediatric kidney disaster data after an earthquake. Serum CK level was significantly associated with Crush-AKI at the levels of >20 950 U/L, but not with death. Adolescent age and initial IVF of less than 3000-4000 mL/m2 BSA were also asscoiated with Crush-AKI. Given that mildly injured victims can survive longer periods in the disaster field, we suggest uninterrupted rescue activity for at least 10 days.

Comprehensive evaluation of patients with primary hyperoxaluria type 1: A nationwide study.

BACKGROUND: Primary hyperoxaluria type 1 (PH1) is characterized by increased endogenous oxalate production and deposition as calcium oxalate crystals. The main manifestations are nephrocalcinosis/nephrolithiasis, causing impaired kidney function. We aimed to evaluate the clinical characteristics and overall outcomes of paediatric PH1 patients in Turkey. METHODS: This is a nationwide, multicentre, retrospective study evaluating all available paediatric PH1 patients from 15 different paediatric nephrology centres in Turkey. Detailed patient data was collected which included demographic, clinical and laboratory features. Patients were classified according to their age and characteristics at presentation: patients presenting in the first year of life with nephrocalcinosis/nephrolithiasis (infantile oxalosis, Group 1), cases with recurrent nephrolithiasis diagnosed during childhood (childhood-onset PH1, Group 2), and asymptomatic children diagnosed with family screening (Group 3). RESULTS: Forty-eight patients had a mutation consistent with PH1. The most common mutation was c.971_972delTG (25%). Infantile oxalosis patients had more advanced chronic kidney disease (CKD) or kidney failure necessitating dialysis (76.9% vs. 45.5%). These patients had much worse clinical course and mortality rates seemed to be higher (23.1% vs. 13.6%). Patients with fatal outcomes were the ones with significant comorbidities, especially with cardiovascular involvement. Patients in Group 3 were followed with better outcomes, with no kidney failure or mortality. CONCLUSION: PH1 is not an isolated kidney disease but a systemic disease. Family screening helps to preserve kidney function and prevent systemic complications. Despite all efforts made with traditional treatment methods including transplantation, our results show devastating outcomes or mortality.

Spontaneous tendon or ligament ruptures in patients undergoing dialysis: First pediatric case report and literature review.

Spontaneous tendon or ligament ruptures are quite rare and mostly associated with chronic systemic diseases such as diabetes mellitus, systemic lupus erythematosus, rheumatoid arthritis, and chronic kidney disease (CKD). In this study, we present the first documented case of a spontaneous rupture of the medial patellofemoral ligament (MPFL) in a pediatric patient. The patient was undergoing long-term peritoneal dialysis (PD) and had a history of severe secondary hyperparathyroidism. Additionally, we discussed spontaneous tendon and ligament ruptures associated with CKD or dialysis through a comprehensive literature review. This case report highlights the importance of recognizing that spontaneous tendon or ligament injuries are not exclusive to adults; children with CKD can also be affected. Several factors including poor parathyroid hormone (PTH) and metabolic acidosis control, prolonged CKD duration and presence of malnutrition play role in the pathogenesis. Early diagnosis is crucial as it allows for timely surgical intervention and leads to a favorable functional recovery.

Chronic Nonbacterial Osteomyelitis Associated With Familial Mediterranean Fever in Children.

OBJECTIVE: Chronic nonbacterial osteomyelitis (CNO) is a noninfectious autoinflammatory bone condition that frequently occurs alongside other inflammatory diseases, such as familial Mediterranean fever (FMF). We aimed to determine the demographic, clinical, laboratory, and radiological characteristics of patients diagnosed with both FMF and CNO. METHODS: We reviewed the medical records of pediatric patients with both CNO and FMF at 3 pediatric rheumatology centers in Turkey from December 2008 to 2022. Patients' demographics, laboratory features, imaging findings, and treatment were recorded. RESULTS: Twelve patients with FMF and CNO were included in the study. Half of them were female. The mean ages at onset for FMF and CNO symptoms were 80 and 116 months, whereas the ages at diagnosis for FMF and CNO were 100 and 125 months, respectively. Ten patients (83.3%) had M694V mutation on at least 1 allele of the Mediterranean fever (MEFV) gene. The most common sites of osteitis were the long bones (58.3%), pelvis (50%), and clavicles (25%). Ten patients (83%) received nonsteroidal anti-inflammatory drugs; 8 (66%) received disease-modifying antirheumatic drugs; biological therapy was administered to 5 patients (41%), who did not respond to these treatments; and all patients received colchicine. CONCLUSION: The increased frequency of FMF in patients with CNO is of interest. Because most patients with CNO and FMF carried a homozygous or combined heterozygous M694V mutation, we speculated that the M694V mutation may play a role in the development of osteitis. Further studies are needed to elucidate the link between FMF and CNO.

Comparative analysis of hospitalizations among patients treated with hemodialysis and peritoneal dialysis in European pediatric nephrology centers: results from a prospective EPDWG/ESPN Dialysis Working Group study.

Background and hypothesis: Hospital admissions in pediatric dialysis patients need to be better studied, and most existing studies are retrospective and based on registry data. This study aimed to analyse and compare hospital admission rates, causes, length of stay (LOS), and outcomes in children treated with peritoneal dialysis (PD) and hemodialysis (HD). Methods: Data from 236 maintenance PD and 138 HD patients across 16 European dialysis centers were collected between 1 July 2017 and 30 June 2018. A total of 178 hospitalized patients (103 PD, 75 HD) were included for further analyses. Results: There were 465 hospitalization events (268 PD, 197 HD) with a rate of 0.39 admissions per 100 patient-days at risk (PDAR) and 2.4 hospital days per 100 PDAR. The admission rates were not significantly different between HD and PD patients. The most common causes of hospitalization were access-related infections (ARI) (17%), non-infectious complications of access (NIAC) (14%), and infections unrelated to access (12%). ARI was the leading cause in PD patients (24%), while NIAC was more common in HD patients (19%). PD patients had more ARIs, diagnostic procedures, and treatment adjustments (P < .05), while HD patients had more NIACs, infections unrelated to access, access placement procedures, and interventional/surgical procedures (P < .001). LOS was longer with acute admissions than non-acute admissions (P < .001). Overall LOS and LOS in the intensive care unit were similar between HD and PD patients. High serum uric acid and low albumin levels were significant predictors of longer LOS (P = .022 and P = .045, respectively). Young age, more significant height deficit, and older age at the start of dialysis were predictors of longer cumulative hospital days (P = .002, P = .001, and P = .031, respectively). Conclusion: Access-related complications are the main drivers of hospitalization in pediatric dialysis patients, and growth and nutrition parameters are significant predictors of more extended hospital stays.

Etanercept-associated episcleritis: a pediatric case report of a paradoxical adverse reaction and review of the literature.

Scleritis is an inflammation of the episcleral and scleral tissues, characterized by injection in both superficial and deep episcleral vessels. When only episcleral tissue is involved, it is referred to as episcleritis. Episcleritis is mainly idiopathic but may be secondary to an underlying rheumatologic disease. Despite being rare, drug-associated episcleritis and scleritis should also be included in the differential diagnosis. Tumor necrosis factor-alpha (TNF-α) inhibitors are generally well-tolerated, but etanercept, in particular, has the potential to cause paradoxical adverse reactions including ocular inflammations, such as uveitis, scleritis, and ocular myositis. Etanercept differs in its mechanism of action from other TNF-α inhibitors as it acts as a decoy receptor, and this may partly explain the more frequently reported etanercept-associated ocular inflammation. Etanercept may also be ineffective in preventing ocular inflammation. However, the dechallenge and rechallenge phenomena have proven there is a causative link between etanercept and new-onset ocular inflammation. We report a case of a 15-year-old boy with enthesitis-related arthritis and familial Mediterranean fever who presented with episcleritis and blepharitis while receiving etanercept treatment and subsequently showed dechallenge and rechallenge reactions. Therefore, physicians should also be aware that episcleritis should be considered a paradoxical adverse reaction to etanercept and can occur in pediatric patients. We also reviewed the English literature to provide an overview and evaluate intervention options.

A clinical overview of paediatric sarcoidosis: Multicentre experience from Turkey.

OBJECTIVES: We aimed to outline the demographic data, clinical spectrum, and treatment approach of sarcoidosis in a large group of patients and sought to figure out the variations of early-onset (EOS) and late-onset paediatric sarcoidosis (LOS). METHODS: The study followed a retrospective-descriptive design, with the analysis of medical records of cases diagnosed as paediatric sarcoidosis. RESULTS: Fifty-two patients were included in the study. The median age at disease onset and follow-up duration were 83 (28.2-119) and 24 (6-48) months, respectively. Ten (19.2%) cases had EOS (before 5th birthday) and 42 (80.7%) cases had LOS. The most common clinical findings at the time of the disease onset were ocular symptoms (40.4%) followed by joint manifestation (25%), dermatological symptoms (13.5%), and features related to multi-organ involvement (11.5%). Anterior uveitis was the most common (55%) one among ocular manifestations. Patients with EOS displayed joint, eye, and dermatological findings more commonly than patients with LOS. The recurrence rate of disease in patients with EOS (5.7%) and LOS (21.1%) were not statistically different (P = .7). CONCLUSIONS: Patients with EOS and LOS may present with variable clinical features and studies addressing paediatric sarcoidosis cases in collaboration between disciplines will enhance the awareness of this rare disease among physicians and assist early diagnosis with lesser complications.

Adhesive small-bowel obstruction as a challenging complication of familial Mediterranean fever: A case-based review.

Familial Mediterranean fever (FMF) is the most common inherited autoinflammatory disorder, characterized by recurrent and self-limiting episodes of fever and serosal inflammation. Recurrent serositis may rarely lead to the formation of adhesions in the peritoneum, which may result in mechanical bowel obstruction. The symptoms, such as abdominal pain and vomiting, may mimic typical FMF attacks, resulting in misdiagnosis and severe morbidity, including strangulation and intestinal necrosis. Physicians are generally aware of other complications associated with FMF but reports on peritoneal adhesions and intestinal obstruction in English-language literature are inadequate to increase clinicians' awareness. Therefore, it is crucial to meticulously evaluate FMF patients presenting with abdominal pain and ileus because these symptoms could be due to adhesive small-bowel obstruction (ASBO). Furthermore, patients presenting with ASBO without a history of abdominal surgery should also be thoroughly evaluated, especially as it could be an initial presentation for an autoinflammatory disease. Herein, we present a pediatric case of FMF with the M694V homozygous mutation, complicated by ASBO while under colchicine treatment. Additionally, we provide a comprehensive review of the available literature on ASBO in FMF.

International comparison and time trends of first kidney transplant recipient characteristics across Europe: an ERA Registry study.

BACKGROUND: The aim of this study was to provide an overview of age, sex and primary renal disease (PRD) distribution among first kidney transplant recipients across Europe. METHOD: The European Renal Association (ERA) Registry database was used to obtain data on patients aged 20 years or older receiving their first kidney transplant between 2010 and 2019 from 12 European countries. The numbers and percentages of recipients in each age, sex and PRD group were calculated by country, donor type and year. RESULTS: In total, 99 543 adults received a first kidney transplant. Overall, 23% of the recipients were 65 years or older, 36% were female, and 21% had glomerulonephritis and 15% diabetes mellitus as PRD. Compared with deceased donor kidney transplant recipients, living donor kidney transplant recipients were less often 65 years or older (13% versus 26%), more often had glomerulonephritis (25% versus 20%) and less often diabetes mellitus (8% versus 17%) as PRD. We found large international differences, which were most prominent for age and PRD and less prominent for sex. Over time, the largest change in recipient characteristics was observed for the percentage of recipients aged 65 years or older, increasing from 18% in 2010 to 28% in 2019 for all countries combined with a similar trend in most countries. CONCLUSION: We observed large differences for age and PRD distribution between recipients of living and deceased donor kidneys and between European countries. Over time, the percentage of older first kidney transplant recipients increased.

Complement gene mutations in children with C3 glomerulopathy: do they affect the response to mycophenolate mofetil?

BACKGROUND: C3 glomerulopathy (C3G) is a complement-mediated disease. Although genetic studies are not required for diagnosis, they are valuable for treatment planning and prognosis prediction. The aim of this study is to investigate the clinical phenotypes, kidney survival, and response to mycophenolate mofetil (MMF) treatment in pediatric C3G patients with and without mutations in complement-related genes. METHODS: Sixty pediatric C3G patients were included, divided into two groups based on complement-related gene mutations. Demographic and clinical-pathological findings, treatment modalities, and outcome data were compared, and Kaplan-Meier analysis was performed for kidney survival. RESULTS: Out of the 60 patients, 17 had mutations. The most common mutation was in the CFH gene (47%). The mean age at diagnosis was higher in the group with mutation (12.9 ± 3.6 vs. 11.2 ± 4.1 years, p = 0.039). While the patients without mutation most frequently presented with nephritic syndrome (44.2%), the mutation group was most likely to have asymptomatic urinary abnormalities (47.1%, p = 0.043). Serum parameters and histopathological characteristics were similar, but hypoalbuminemia was more common in patients without mutation. During 45-month follow-up,10 patients progressed to chronic kidney disease stage 5 (CKD5), with 4 having genetic mutation. The time to develop CKD5 was longer in the mutation group but not significant. MMF treatment had no effect on progression in either group. CONCLUSIONS: This study is the largest pediatric C3G study examining the relationship between genotype and phenotype. We showed that the mutation group often presented with asymptomatic urinary abnormalities, was diagnosed relatively late but was not different from the without mutation group in terms of MMF treatment response and kidney survival.

Rituximab use in paediatric nephrology practice in Türkiye: TRTX.

AIM: Rituximab (RTX) is a genetically engineered chimeric monoclonal antibody which binds directly to CD20 antigen and mediates inhibition of B cell development. Although RTX has been widely used in paediatric nephrology, there is no routine protocol for its use. In this study, paediatric nephrologists in Türkiye were asked to fill out a questionnaire to understand their practice in using RTX. This study aimed to determine common practices and clarify the uncertainties regarding the use of RTX in paediatric nephrology. METHODS: This was a nationwide, multicenter, retrospective cohort study based on data evaluating the use of RTX in paediatric nephrology practice. An online questionnaire was sent to all paediatric nephrology centers in Türkiye. The questionnaire forms included information about how many patients in total applied RTX treatment, for which indications they use RTX, and whether they made any preparations before using RTX. RESULTS: According to this survey on RTX use in Türkiye, paediatric nephrologists use it most commonly in SSNS and followed by SRNS, ABMR, SLE and AAV, respectively. Dosing was highly standard but there is significant heterogeneity in pre-exposure tests and patient monitoring in the clinical practice of RTX. Also, the rate of encountering RTX-related allergic and infectious side effects at least once during the professional experience of our physicians can be quite high. CONCLUSION: There is an increasing need for the preparation of a guideline on the indications for RTX use for each diagnosis, posology, and the practices to be performed before and after infusion.