The aim of this study was to compare the clinical and demographic features and evaluate the phenotypic and genotypic differences of pediatric familial Mediterranean fever (FMF) patients according to ...their age at disease onset.
Records of 854 patients who were diagnosed with FMF between 2006 and 2017 were evaluated. Patients were divided into 2 subgroups according to their age at disease onset. Group 1 comprised FMF patients who had experienced their first attack at 2 years or younger (younger onset), and group 2 comprised FMF patients who had experienced their first attack at older than 2 years.
There were 155 patients in group 1 and 699 patients in group 2. Delay in diagnosis, attack frequency, duration of attacks, fever, chest pain, erysipelas-like erythema, incidence of family history, anti-interleukin 1 therapy use, and M694V homozygous and M680I homozygous mutations were significantly higher in group 1, whereas arthralgia and abdominal pain were significantly higher in group 2. There were no significant differences in arthritis, amyloidosis, and protracted febrile myalgia between the groups. The colchicine dose at last visit and Pras activity score were higher in group 1.
It seems that FMF patients with a younger onset has a more severe disease course. They needed higher doses of colchicine to control the attacks. M694V and M680I homozygous mutations presented more frequently in younger-onset FMF patients. Increased awareness of physicians of the early presentation of FMF may prevent delays in FMF diagnosis.
Background
The aim of this study was to evaluate the efficacy and safety of anti‐interleukin‐1 (IL‐1) therapies in colchicine‐resistant pediatric patients with familial Mediterranean fever (FMF).
...Methods
In this study, we retrospectively evaluated 656 children with FMF and 27 patients who had been treated with anti‐IL‐1 therapies (anakinra/canakinumab) . Clinical and laboratory features, MEFV gene mutations, treatment responses were investigated.
Results
Twenty of the patients were treated with anakinra (the treatment of 6 patients who initially used anakinra was switched to canakinumab in the follow‐up period), and 13 patients were treated with canakinumab. Clinical symptom and severity scores decreased in all patients A decrease in acute phase reactants was also observed in patients. A total of 18 (66%) patients had a M694V homozygous mutation, while 24 (89%) patients had a M694V mutation, at least in one allele.
Conclusions
FMF patients with colchicine resistance may progress to amyloidosis. IL‐1 antagonist treatment could be used safely with a favorable outcome in pediatric patients with FMF resistance to colchicine therapy and/or who have renal amyloidosis.
Background
Atypical hemolytic uremic syndrome (aHUS) is a chronic disease characterized by thrombotic microangiopathy and a high risk of end-stage kidney disease. Dysregulation and/or excessive ...activation of the complement system results in thrombotic microangiopathy. Interest in extrarenal manifestations of aHUS is increasing. This study aimed to determine the clinical characteristics of patients with extrarenal manifestations of aHUS in childhood.
Methods
This study included 70 children with extrarenal manifestations of HUS from the national Turkish aHUS Registry. The demographics, clinical characteristics, genetic test results, all treatments, and renal/hematologic status of aHUS patients with extrarenal involvement were recorded.
Results
The most common extrarenal manifestation was neurological system involvement (
n
= 46 27.2%), followed by gastrointestinal (
n
= 20 11.8%), cardiovascular (
n
= 12 7%), and respiratory (
n
= 12 7%) involvement. The patients with neurological involvement had a higher mortality rate and a lower estimated glomerular filtration rate (eGFR) than the other patients at last follow-up. Eculizumab (with or without plasma exchange/plasma infusion) treatment increased the renal and hematologic recovery rates.
Conclusions
The most common and serious extrarenal manifestation of aHUS is neurological involvement and treatment outcome findings presented herein are important to all relevant clinicians.
There is no information on renal vein thrombosis induced by COVID-19 infection in a neonate. Few cases of renal vein thrombosis caused by COVID-19 infection have been reported in predominantly adult ...patients. On day 25 after birth, a newborn whose mother was infected with COVID-19 had renal vein thrombosis. We believed that our patient’s renal vein thrombosis was caused by postnatal transmission of the COVID-19 infection that the mother had acquired during birth. The clinical and radiologic findings of these unusual renal complications in a neonate, as well as treatment options, are presented.
Familial Mediterranean fever (FMF) is the most common and autosomal recessive inherited autoinflammatory disease. The most common signs and symptoms are fever, abdominal pain, chest pain, and ...arthritis. The aim of this study was to describe the clinical, laboratory and genetic differences between pediatric FMF patients with and without chest pain.
Between January 2006 and January 2022, 1134 patients with FMF were analyzed retrospectively. Patients were divided into two groups including those with and without recurrent chest pain. These groups were compared in demographic, clinical, treatment, and MEFV gene analyses.
A hundred and sixty-two (14.3%) patients had recurrent chest pain. In patients with recurrent chest pain, the age of onset of symptoms was younger (p=0.003), and the family history of FMF was higher (p=0.002). Patients with chest pain had a higher annual attack frequency (p < 0.001), a longer attack duration (p < 0.001), and higher Pras disease activity scores (p < 0.001). The colchicine dose used in the treatment was higher in FMF patients with chest pain (p=0.005), and anti-IL-1treatment was higher (p < 0.001). M694V homozygous mutation was found more frequently (p=0.001), whereas M694V/V726A mutation was found less frequently in patients with recurrent chest pain (p=0.017).
Patients with recurrent chest pain seem to have early onset symptoms, often are more likely to have family history, and have a higher disease severity. In addition, the presence of homozygous M694V mutation is more common in patients with chest pain.
Atypical hemolytic uremic syndrome (aHUS) is a devastating disease with significant morbidity and mortality. Its genetic heterogeneity impacts its clinical presentation, progress, and outcome, and ...there is no consensus on its clinical management.
To identify the characteristics of aHUS in Turkish children, an industry-independent registry was established for data collection that includes both retrospective and prospective patients.
In total, 146 patients (62 boys, 84 girls) were enrolled; 53 patients (36.3%) were less than 2 years old at initial presentation. Among the 42 patients (37.1%) whose mutation screening was complete for CFH, CFI, MCP, CFB, C3, DGKE, and CHFR5 genes, underlying genetic abnormalities were uncovered in 34 patients (80.9%). Sixty-one patients (41.7%) had extrarenal involvement. During the acute stage, 33 patients (22.6%) received plasma therapy alone, among them 17 patients (51.5%) required dialysis, and 4 patients (12.1%) were still on dialysis at the time of discharge. In total, 103 patients (70.5%) received eculizumab therapy, 16 of whom (15.5%) received eculizumab as a first-line therapy. Plasma therapy was administered to 84.5% of the patients prior to eculizumab. In this group, renal replacement therapy was administered to 80 patients (77.7%) during the acute period. A total of 3 patients died during the acute stage. A total of 101 patients (77.7%) had a glomerular filtration rate >90 mL/min/1.73 m
at the 2-year follow-up.
The Turkish aHUS registry will increase our knowledge of patients with aHUS who have different genetic backgrounds and will enable evaluation of the different treatment options and outcomes.
The aim of this prospective, multicenter study was to define the etiology and clinical features of acute kidney injury (AKI) in a pediatric patient cohort and to determine prognostic factors. ...Pediatric-modified RIFLE (pRIFLE) criteria were used to classify AKI. The patient cohort comprised 472 pediatric patients (264 males, 208 females), of whom 32.6% were newborns (median age 3 days, range 1–24 days), and 67.4% were children aged >1 month (median 2.99 years, range 1 month–18 years). The most common medical conditions were prematurity (42.2%) and congenital heart disease (CHD, 11.7%) in newborns, and malignancy (12.9%) and CHD (12.3%) in children aged >1 month. Hypoxic/ischemic injury and sepsis were the leading causes of AKI in both age groups. Dialysis was performed in 30.3% of newborns and 33.6% of children aged >1 month. Mortality was higher in the newborns (42.6 vs. 27.9%;
p
< 0.005). Stepwise multiple regression analysis revealed the major independent risk factors to be mechanical ventilation relative risk (RR) 17.31, 95% confidence interval (95% CI) 4.88–61.42, hypervolemia (RR 12.90, 95% CI 1.97–84.37), CHD (RR 9.85, 95% CI 2.08–46.60), and metabolic acidosis (RR 7.64, 95% CI 2.90–20.15) in newborns and mechanical ventilation (RR 8.73, 95% CI 3.95–19.29), hypoxia (RR 5.35, 95% CI 2.26–12.67), and intrinsic AKI (RR 4.91, 95% CI 2.04–11.78) in children aged >1 month.
Definitive sample sizes for clinical trials in rare diseases are usually infeasible. Bayesian methodology can be used to maximise what is learnt from clinical trials in these circumstances. We ...elicited expert prior opinion for a future Bayesian randomised controlled trial for a rare inflammatory paediatric disease, polyarteritis nodosa (MYPAN, Mycophenolate mofetil for polyarteritis nodosa).
A Bayesian prior elicitation meeting was convened. Opinion was sought on the probability that a patient in the MYPAN trial treated with cyclophosphamide would achieve disease remission within 6-months, and on the relative efficacies of mycophenolate mofetil and cyclophosphamide. Expert opinion was combined with previously unseen data from a recently completed randomised controlled trial in ANCA associated vasculitis.
A pan-European group of fifteen experts participated in the elicitation meeting. Consensus expert prior opinion was that the most likely rates of disease remission within 6 months on cyclophosphamide or mycophenolate mofetil were 74% and 71%, respectively. This prior opinion will now be taken forward and will be modified to formulate a Bayesian posterior opinion once the MYPAN trial data from 40 patients randomised 1:1 to either CYC or MMF become available.
We suggest that the methodological template we propose could be applied to trial design for other rare diseases.
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