Adem Polat

Results from a multicentre international registry of familial Mediterranean fever: impact of environment on the expression of a monogenic disease in children

Background and aim Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by mutations of the MEFV gene. We analyse the impact of ethnic, environmental and genetic factors on the severity of disease presentation in a large international registry. Methods Demographic, genetic and clinical data from validated paediatric FMF patients enrolled in the Eurofever registry were analysed. Three subgroups were considered: (i) patients living in the eastern Mediterranean countries; (ii) patients with an eastern Mediterranean ancestry living in western Europe; (iii) Caucasian patients living in western European countries. A score for disease severity at presentation was elaborated. Results Since November 2009, 346 FMF paediatric patients were enrolled in the Eurofever registry. The genetic and demographic features (ethnicity, age of onset, age at diagnosis) were similar among eastern Mediterranean patients whether they lived in their countries or western European countries. European patients had a lower frequency of the high penetrance M694V mutation and a significant delay of diagnosis (p<0.002). Patients living in eastern Mediterranean countries had a higher frequency of fever episodes/year and more frequent arthritis, pericarditis, chest pain, abdominal pain and vomiting compared to the other two groups. Multivariate analysis showed that the variables independently associated with severity of disease presentation were country of residence, presence of M694V mutation and positive family history. Conclusions Eastern Mediterranean FMF patients have a milder disease phenotype once they migrate to Europe, reflecting the effect of environment on the expression of a monogenic disease.

Interleukin-8 and Its Receptors in Human Milk from Mothers of Full-Term and Premature Infants.

In addition to its nutritional benefits, human milk also has bioactive elements. Limited immunological functions of newborns are supported and altered by the immunological elements of mother milk. Chemokines are of importance among these immune factors. Interleukin-8 (IL-8) has been demonstrated in mothers milk, and its receptors, CXC chemokine receptors (CXCR)-1 and CXCR-2, were detected on cells, responsible for immunological reactions and mammary glandular cells. The soluble forms of these receptors are yet to be described in human milk. In this study, it was aimed to assess the IL-8 levels and the concentrations of its receptors in colostrum and mature mothers milk in regard to preterm and term delivery. The results of this study indicated a decline in IL-8 levels with the lactation stage, but no difference was observed between term and preterm mothers milk. Regarding the CXCR-1 and CXCR-2, the concentrations of these receptors were similar in both colostrum and mature milk. Furthermore, there was not any significant difference between term and preterm mothers milk. In conclusion, this is the first study to investigate the concentrations of CXCR-1 and CXCR-2 with the levels of IL-8 in colostrum and mature human milk of term and preterm newborns. The alterations in IL-8 levels were similar in some of the studies reported. CXCR-1 and CXCR-2 levels did not demonstrate any significant difference. Further studies are required to investigate the soluble forms of these receptors and their relation to IL-8 with larger cohort.

Comparison of the efficacy of once- and twice-daily colchicine dosage in pediatric patients with familial Mediterranean fever – a randomized controlled noninferiority trial

BackgroundIn this study, we examined the efficacy and safety of a once-daily dosage schema of colchicine compared with a twice-daily dosage schema in pediatric patients with familial Mediterranean fever (FMF).MethodsIn this 24-week, multicenter, randomized controlled noninferiority trial, pediatric patients newly diagnosed with FMF carrying a homozygous or compound heterozygous mutation and not receiving any treatment were included. Patients were randomly assigned using a block randomization method to receive treatment with a once- or twice-daily dosage. Clinical and laboratory characteristics and medication side effects were recorded and compared between groups. The study was carried out in compliance with Good Clinical Practice and the Consolidated Standards for Reporting of Trials (CONSORT) statement.ResultsA total of 92 patients were selected, and 79 patients completed the study. There were 42 patients in the once-daily dosage group and 37 in the twice-daily dosage group. The results indicated that the once-daily dosage was not inferior to the twice-daily dosage regarding decrease in attack frequency and duration as well as improvement in clinical findings and Mor severity scores. Alterations in laboratory findings indicating inflammation, such as erythrocyte sedimentation rate, C-reactive protein, and serum amyloid A, were similar in both groups. The rates of drug side effects were similar between the once- and twice-daily dosage groups, implying comparable safety of colchicine, with the exception of diarrhea, which was slightly higher in the once-daily dosage group.ConclusionsUsing colchicine with either a once- or twice-daily dosage provides similar clinical and laboratory improvements. Considering both efficacy and safety, colchicine can be prescribed with a once-daily dosage.Trial Registration IDClinicalTrials.gov identifier NCT02602028. Registered 5 November 2015.

Evaluation of Etanercept Treatment in Newborn Rat Model with Hyperoxic Lung Injury

ABSTRACT Background: Many factors contribute to the development of BPD basically by increasing inflammation in preterm lungs. However, premature neonates have insufficient anti-inflammatory capacity. We aimed to evaluate the effect of etanercept, an anti-TNF agent, on BPD development in newborn rat model with hyperoxia-induced lung injury. Methods: Thirty-two newborn rats were divided into 3 groups as control group (Group 1, n = 11), hyperoxia + placebo group (Group 2, n = 10), and hyperoxia + etanercept group (Group 3, n = 11). Histopathological and biochemical analysis were performed in order to assess inflammation and oxidative stress. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities, and malondialdehyde (MDA) levels were studied, histopathological scoring and radial alveolar count were applied in lung tissue. Lamellar body membrane protein, vascular endothelial growth factor (VEGF), nuclear factor-kappaB (NF-κB) gene expressions were studied in immunohistochemical evaluation of tissue samples. All three groups were compared with each other in terms of all parameters. Results: SOD and GSH-Px activities were significantly higher, whereas MDA levels were lower in group 3, compared to group 2 (p < 0.001). Histopathological scores were lower, lamellar body membrane protein expression and radial alveolar count were higher in group 3 (p < 0.05). NF-κB expression was higher in group 2, but lower in group 3 in comparison with group 1. Expression of VEGF was decreased in group 2 but came close to group 1 with etanercept treatment in group 3. Conclusions: We found etanercept treatment to be protective in newborn rats with hyperoxia-induced lung damage.

PReS-FINAL-2328: Developing and validating the new severity score for FMF

One of the main features, in the follow-up of a patient with a chronic disorder is severity. Definition in severity is quite difficult since the disease manifests with various clinical and laboratory features. On the other hand, there have been many articles reported in literature about the lack of consistency between currently used severity scores such as Mor, Pras and Tel Hashomer criteria.

PReS-FINAL-2204: Developing of a new scale for assessing the adherence to colchicines treatment in pediatric patients with FMF

Familial Mediterranean Fever (FMF) is a disease characterized by attacks and colchicine is the medication considered most effective in reducing the intensity and frequency of attacks. Adherence to the medication regiment is important not only to manage FMF symptoms, but also to prevent amyloidosis.

Behçet disease: evaluation of clinical manifestations in Turkish children

Results In 54 patients the mean age at the first symptom was 117.50±45.20 months. BD was suspected at a mean age of 143.56±39.63 months. The mean delay between the first symptom and BD suspicion was 27.36±27.15 months. The most common manifestations were oral ulcer 96.3% (n=52), uveitis 46.3% (n=25), genital ulcer 37% (n=20), pustuler lesion 37% (n=20), erythema nodosum 24.1%(n=13) respectively. Bilateral uveitis was found in 27.8% (n=15) patients. Pathergy phenomen was positive in 37% (n=20) patients. Family history of BD was present in 38.9% (n=21) patients. HLA-B51 carrier rate was 53.7% (n=29). BSAS was assessed for the 52 patients in our cohort and a moderate correlation between the BSAS and PGA was demonstrated (r=0.305, p=0.025).

Oculoauriculofrontonasal Dysplasia Syndrome With Additional Clinical Features

Oculo-auriculo-vertebral spectrum and frontonasal dysplasia are two well-known examples of dysmorphology syndromes. Oculoauriculofrontonasal syndrome (OAFNS) is a clinical entity involving the characteristics of both OAVS and FND and is thought to be a result of the abnormal development of structures in the first and the second branchial arches, including the abnormal morphogenesis of maxillary processes. Herein we report a case of OAFNS with cliteral hypertrophy, premaxillary teeth, and inguinal hernia, features not previously reported in the literature.

Developing of a new scale for assessing the adherence to colchicine treatment in pediatric patients with FMF.

Familial Mediterranean Fever (FMF) is a disease characterized by attacks and colchicine is the medication considered most effective in reducing the intensity and frequency of attacks. Adherence to the medication regiment is important not only to manage FMF symptoms, but also to prevent amyloidosis.

AB0968 Adrenomedullin Levels in Patients with Familial Mediterranean Fever: A Long Term Follow-Up

Background Familial Mediterranean Fever (FMF) is the most common periodic fever syndrome, characterized by recurrent fever and serositis attacks. It has been shown that there might be an ongoing subclinical inflammation between attacks. Adrenomedullin (ADM) is synthesized in endothelium, and has been shown to have high levels in patients with inflammation such as FMF. Colchicine is the treatment of choice and given once or twice daily depending on expert opinion. Objectives In this study, it was aimed to investigate ADM as a marker for inflammation in pediatric patients with FMF who are using colchicine in different dosage schema Methods Pediatric patients with FMF diagnosed clinically and genetically confirmed were included in the study. The colchicine was started in one or two doses randomly. The clinical and laboratory parameters were assessed on six clinical visits made every two months. After the third visit the dosing schema was changed to twice or once depending on the schema at the beginning. Results A total of 37 patients (female/male ratio: 0.94) were included in the study. Mean age of patients, age at disease onset, and age at diagnosis were 7.78±2.00, 5.05±3.04, and 7.51±2.66 years, respectively. Twenty patients received colchicine in once daily dosage while 17 patients had in twice-daily dosage at the beginning of the study. There were 10 patients with heterozygote and 27 with homozygote MEFV mutations. After the treatment was started all patients demonstrated improvement in clinical and laboratory findings such as erythrocyte sedimentation rate and C-reactive protein. However, ADM levels did not show any correlation with ESR and CRP levels. Mean ADM levels in six consecutive visits were as follows, first 322.19±161.92 ng/L; second 330.50±189.63 ng/L; third 339.54±168.03 ng/L; forth 378.11±177.63 ng/L; fifth 328.91±172.30 ng/L and sixth 326.25±165.87 ng/L. ADM levels were similar in all visits (p=0.954) and did not show any difference between the first and second three visits i.e. before and after changing the dosage schema (p=0.593). Conclusions The results indicated that patients using colchicine in once or twice daily doses did not show any significant difference according to the clinical and laboratory findings and had similar effects in controlling disease manifestations. ADM levels did not demonstrate any alterations in all visits that may suggest the continuation of subclinical inflammation in these patients. Disclosure of Interest None declared