Research: The Latest

Research: The Latest2019-05-23T10:46:23+00:00
  • Effect of oral Colchicine on Peripapillary retinal nerve fiber layer thickness in patients with familial Mediterranean fever.

    Related ArticlesEffect of oral Colchicine on Peripapillary retinal nerve fiber layer thickness in patients with familial Mediterranean fever. BMC Ophthalmol. 2018 Feb 05;18(1):27 Authors: Tanyıldız B, Tezcan ME, Kandemir B, Günaydın NT, Göktaş E, Tangılntız A, Arsan AK Abstract BACKGROUND: The purpose of this study is to investigate whether oral colchicine has an effect on peripapillary retinal nerve fiber layer (pRNFL) thickness of familial Mediterranean fever (FMF) patients. METHODS: We conducted a cross sectional study by comparing pRNFL thickness of FMF patients on colchicine (treated group), newly diagnosed colchicine naïve FMF patients (untreated group) and healthy controls. The study included 66 FMF patients and 32 healthy control subjects. Treated FMF patients were grouped according to colchicine use, duration of use and dosage. pRNFL thickness of the patients and controls were measured by using optical coherence tomography and the measurements were compared. RESULTS: No statistically significant difference was found between the pRNFL thickness in untreated group, treated group and the healthy control group (all p > 0.05). No statistically significant difference was found between pRNFL thickness in the healthy control group and FMF patients grouped according to duration or dosage of colchicine use (all p > 0.05). CONCLUSIONS: According to our study, FMF and oral colchicine use had no statistically significant effect on pRNFL thickness.PMID: 29402238 [PubMed - indexed for MEDLINE […]

  • Alteration of the microRNA expression profile in familial Mediterranean fever patients.

    Related ArticlesAlteration of the microRNA expression profile in familial Mediterranean fever patients. Clin Exp Rheumatol. 2017 Nov-Dec;35 Suppl 108(6):90-94 Authors: Akkaya-Ulum YZ, Balci-Peynircioglu B, Karadag O, Eroglu FK, Kalyoncu U, Kiraz S, Ertenli AI, Özen S, Yilmaz E Abstract OBJECTIVES: Phenotypic heterogeneity in familial Mediterranean fever (FMF) disease indicated that FMF is not a simple monogenic disease. Therefore it has been suggested that epigenetic factors can be one of the reason for the variations. We undertook this study to test potential involvement of miRNAs in the pathogenesis of FMF. METHODS: miRNA array was performed on whole blood RNA samples from 6 healthy controls (-/-), 6 FMF patients (M694V/M694V), 6 carriers who displayed the disease phenotype (M694V/-) and 6 healthy carriers (M694V/-). The raw data was analysed by Multi Experiment Viewer (MeV) and candidate miRNAs were determined according to fold change (more than 2.0 or less than -2.0). The validation of differentially expressed miRNAs was done by qRT-PCR. Then we performed pathway analyses with using bioinformatics tools. RESULTS: 14 miRNAs were found to be significant among groups through the analysis with MeV. miR-20a-5p, miR-197-3p, let-7d-3p and miR-574-3p were found to be associated with inflammatory pathway related genes according to DAVID analysis. MiR-20a-5p (FDR: 0,00, FCH: 5.55) was significantly up regulated whereas miR-197-3p (FDR: 0,00, FCH: -2.27) was down regulated in homozygotes patients. Both let-7d-3p (FDR: 0.00, FCH: 28.75) and miR-574-3p (FDR: 0.00, FCH: 3.95) were up regulated in heterozygote patients group. CONCLUSIONS: We showed that there are several differentially expressed miRNAs both in homozygote and heterozygote FMF patients compared to controls and healthy carriers. Thus we suggest that these miRNAs, related with inflammatory pathways may be responsible for the expression of the disease in FMF.PMID: 29224588 [PubMed - indexed for MEDLINE […]

  • Outcomes of long term treatments of type I hereditary angioedema in a Turkish family.

    Related ArticlesOutcomes of long term treatments of type I hereditary angioedema in a Turkish family. An Bras Dermatol. 2017 Sep-Oct;92(5):655-660 Authors: Akoglu G, Kesim B, Yildiz G, Metin A Abstract BACKGROUND: Hereditary angioedema is a rare autosomal dominantly inherited immunodeficiency disorder characterized by potentially life-threatening angioedema attacks. OBJECTIVE: We aimed to investigate the clinical and genetic features of a family with angioedema attacks. METHODS: The medical history, clinical features and C1-INH gene mutation of a Turkish family were investigated and outcomes of long-term treatments were described. RESULTS: Five members had experienced recurrent swellings on the face and extremities triggered by trauma. They were all misdiagnosed as familial Mediterranean fever (FMF) depending on frequent abdominal pain and were on colchicine therapy for a long time. They had low C4 and C1-INH protein concentrations and functions. A mutation (c.1247T>A) in C1-INH gene was detected. They were diagnosed as having hereditary angioedema with C1-INH deficiency (C1-INH hereditary angioedema) for the first time. Three of them benefited from danazol treatment without any significant adverse events and one received weekly C1 esterase replacement treatment instead of danazol since she had a medical history of thromboembolic stroke. STUDY LIMITATIONS: Small sample size of participants. CONCLUSION: Patients with C1-INH hereditary angioedema may be misdiagnosed as having familial Mediterranean fever in regions where the disorder is endemic. Medical history, suspicion of hereditary angioedema and laboratory evaluations of patients and their family members lead the correct diagnoses of hereditary angioedema. Danazol and C1 replacement treatments provide significant reduction in hereditary angioedema attacks.PMID: 29166502 [PubMed - indexed for MEDLINE […]

  • Recurrent pleural effusion is an important diagnostic clue to distinguish familial Mediterranean fever from Behçet's disease.

    Related ArticlesRecurrent pleural effusion is an important diagnostic clue to distinguish familial Mediterranean fever from Behçet's disease. Clin Exp Rheumatol. 2017 Nov-Dec;35 Suppl 108(6):135 Authors: Yamaguchi F, Tajika M, Inoue D, Shikama Y, Kishida D, Nakamura A PMID: 29148417 [PubMed - indexed for MEDLINE […]

  • Exacerbation of Behçet's syndrome and familial Mediterranean fever with menstruation.

    Related ArticlesExacerbation of Behçet's syndrome and familial Mediterranean fever with menstruation. Clin Exp Rheumatol. 2017 Nov-Dec;35 Suppl 108(6):95-99 Authors: Guzelant G, Ozguler Y, Esatoglu SN, Karatemiz G, Ozdogan H, Yurdakul S, Yazici H, Seyahi E Abstract OBECTIVES: Menstruation triggers several conditions such as migraine, recurrent aphthous stomatitis and acne vulgaris in healthy individuals. There is evidence that Behçet's syndrome (BS) and familial Mediterranean fever (FMF) may exacerbate during menstruation. The aim is to assess whether BS and FMF patients experience menstrual flares. METHODS: Females of reproductive age with BS and FMF seen consecutively at the outpatient clinic of Cerrahpasa Medical Faculty at Istanbul, as well as apparently healthy hospital workers were studied using a standardised questionnaire. BS patients were asked whether they experienced increased skin-mucosa lesions during the menstrual period. A similar questionnaire assessing this time the frequency of abdominal pain, chest pain and fever attacks was given to the patients with FMF. The healthy controls received both questionnaires. RESULTS: A total of 200 BS patients, 240 FMF patients and 250 healthy controls were studied. The most commonly reported symptom among both BS patients (51%) and healthy controls (62%) was the acneiform lesion. At least 79% patients with FMF reported attacks with menstruation, notably abdominal pain which, majority thought, could be differentiated from dysmenorrhea. Additionally, 76% of healthy controls reported having abdominal pain consistent most probably with dysmenorrhea. CONCLUSIONS: This survey showed that, in 68% of the patients with BS at least one skin mucosa lesion was exacerbated with menstruation, this was most commonly acneiform lesion. Menstruation had a slightly stronger effect on FMF, triggering at least one symptom in 79%. The main limitation of the study was the self-reported assessment methodology.PMID: 29148415 [PubMed - indexed for MEDLINE […]

  • A high and equal prevalence of the Q703K variant in NLRP3 patients with autoinflammatory symptoms and ethnically matched controls.

    Related ArticlesA high and equal prevalence of the Q703K variant in NLRP3 patients with autoinflammatory symptoms and ethnically matched controls. Clin Exp Rheumatol. 2017 Nov-Dec;35 Suppl 108(6):82-85 Authors: Lidar M, Brantz Y, Shinar Y, Reznik-Wolf H, Livneh A, Ben Zvi I, Cohen R, Berkun Y, Hashkes PJ, Peleg H, Kessel A, Slobodin G, Rozenbaum M, Goldzweig O, Pras E Abstract OBJECTIVES: Cryopyrin associated periodic syndromes (CAPS) comprise a spectrum of autoinflammatory disorders of varying severity caused by mutations in the NLRP3 gene. The NLRP3-Q703K allele has been reported both as a functional polymorphism and as a low penetrance mutation. METHODS: To describe the clinical phenotype of subjects with the Q703K allele and to report the frequency of this allele among patients with autoinflammatory symptoms and healthy controls. To this end, a cohort of 10 ethnically-matched controls per each Q703K-carrying patient, was composed. RESULTS: Ninety patients suspected of harboring a systemic autoinflammatory disease (SAID), exclusive of FMF, were referred to our center for genotyping between 2012 and 2015. Fourteen of them (15.5%) were found to carry the Q703K allele, compared to 22 of 130 (16.9%) healthy, ethnically matched controls. CONCLUSIONS: The similar carrier rate of the NLRP3-Q703K allele among patients with manifestations of a SAID and an ethnically matched control group suggest that this variant, does not determine the clinical phenotype. This reiterates the importance of testing a control group to avoid erroneously attributing a causative role to a gene polymorphism.PMID: 29148409 [PubMed - indexed for MEDLINE […]

  • Other autoinflammatory disease genes in an FMF-prevalent population: a homozygous MVK mutation and a novel heterozygous TNFRSF1A mutation in two different Turkish families with clinical FMF.

    Related ArticlesOther autoinflammatory disease genes in an FMF-prevalent population: a homozygous MVK mutation and a novel heterozygous TNFRSF1A mutation in two different Turkish families with clinical FMF. Clin Exp Rheumatol. 2017 Nov-Dec;35 Suppl 108(6):75-81 Authors: Karacan İ, Uğurlu S, Tolun A, Tahir Turanlı E, Ozdogan H Abstract OBJECTIVES: No MEFV mutations are detected in approximately 10% of the patients with clinical FMF in populations where the disease is highly prevalent. Causative mutations were searched in other genes in two such families with "MEFV negative clinical FMF". METHODS: Father and daughter of family A had attacks of fever, abdominal pain and AA amyloidosis. The two sibs of family B complained of febrile episodes with abdominal pain and arthritis. The patients were clinically investigated. Exome analysis in the daughter in family A and linkage analysis and candidate gene sequencing for the members of family B were performed. All patients were re-evaluated in the light of the genetic findings. RESULTS: In the daughter in family A, filtering of the exome file for variants in 25 autoimmune/inflammatory disease-related genes revealed two heterozygous missense variants in TNFRSF1A, novel p.Cys72Phe and frequent p.Arg121Gln. In family B, novel, homozygous missense p.Cys161Arg in MVK was identified. A clinical re-evaluation of the patients revealed a phenotype consistent with FMF rather than TRAPS in family A and an overlap of FMF with HIDS in family B. CONCLUSIONS: In high risk populations of FMF a proportion of patients without MEFV mutations may carry causative mutations in other genes, and the clinical findings may not be fully consistent with the phenotype expected of the mutation identified but rather resemble FMF or an overlap syndrome.PMID: 29148404 [PubMed - indexed for MEDLINE […]

  • Comparison of patients with familial Mediterranean fever accompanied with sacroiliitis and patients with juvenile spondyloarthropathy.

    Related ArticlesComparison of patients with familial Mediterranean fever accompanied with sacroiliitis and patients with juvenile spondyloarthropathy. Clin Exp Rheumatol. 2017 Nov-Dec;35 Suppl 108(6):124-127 Authors: Sönmez HE, Batu ED, Demir S, Bilginer Y, Özen S Abstract OBJECTIVES: Familial Mediterranean fever (FMF) is the most common autoinflammatory disease manifesting with self-limited recurrent febrile attacks and polyserositis. Acute recurrent monoarthritis is the most common form of musculoskeletal involvement in FMF; however, up to 5% of FMF patients may develop chronic joint diseases including sacroiliitis. It is difficult to distinguish whether sacroiliitis is a musculoskeletal finding of FMF or whether this is the coexistence of two diseases, FMF and SpA. In this study, we aimed to evaluate FMF patients with sacroiliitis, and compare their features with juvenile spondyloarthropathy (SpA) patients, all of whom had sacroiliitis. METHODS: 15 paediatric FMF patients with sacroiliitis and 30 patients with juvenile SpA followed between 2014-2016 at the Department of Paediatric Rheumatology at Hacettepe University, Ankara, were included in the study. RESULTS: The median (min-max) age at diagnosis of sacroiliitis was 11 (7-15) for FMF+sacroiliitis, and 11.5 (7-16) years for juvenile SpA patients. All patients suffered from hip pain and morning stiffness. Only two FMF+sacroiliitis patients had enthesitis, while nearly half of juvenile SpA patients (46.7%) had enthesitis. Four FMF patients suffered from lower back pain, although none of them had spinal involvement. On the other hand, approximately one third of juvenile SpA patients had spinal involvement. The median white blood cell count, erythrocyte sedimentation rate, and C reactive protein values in FMF+sacroiliitis patients were higher (10.1x103/mm3 vs 7.8x103/mm3, p = 0.002; 41 vs 28 mm/h, p<0.001; 4.6 vs 1.3 mg/dl, p<0.001; respectively) than juvenile SpA patients. HLA B27 positivity was more common in juvenile SpA than FMF+sacroiliitis patients (86.6% vs 26.7%, respectively, p=0.001). The most common MEFV (MEditerranean FeVer) mutation was M694V in FMF patients. All juvenile SpA patients but one were negative for MEFV mutations. One juvenile SpA patient was heterozygous for E148Q. CONCLUSIONS: We demonstrated that paediatric patients with FMF+sacroiliitis showed different characteristics (higher inflammatory markers, less frequent spinal and enthesitis involvement and HLA-B27 positivity) from patients with juvenile SpA. Whether FMF is a triggering factor for SpA or sacroiliitis is a feature of FMF, is still a matter of debate.PMID: 28980897 [PubMed - indexed for MEDLINE […]

  • The liver in familial Mediterranean fever: is it involved?

    Related ArticlesThe liver in familial Mediterranean fever: is it involved? Clin Exp Rheumatol. 2017 Nov-Dec;35 Suppl 108(6):108-112 Authors: Ben-Chetrit E, Yazici H Abstract OBJECTIVES: Familial Mediterranean fever (FMF) is characterised by recurrent attacks of fever and serositis. It may affect the peritoneum, pleura, synovia and the skin. Usually the liver is intact in FMF. Recently, this concept was challenged by some groups which claimed that hepatitis is a feature of FMF and that non-alcoholic liver disease (NAFLD) and cryptogenic cirrhosis are more common among FMF patients. Scope of this paper is to critically review the relevant literature and to answer the question whether or not the liver is involved in FMF. METHODS: We used Medline, Embase, Scopus and Web of Science database for searching articles dealing with FMF and the liver since 1960. We also reviewed some manuscripts which were not identified by the above searching engines. RESULTS: Some cases reported that hepatitis is a feature of FMF based upon transaminase elevations without liver biopsy. Due to this questionable diagnosis and the paucity of similar reports, it seems that hepatitis is not a feature of FMF. Cryptogenic cirrhosis is considered as the end stage of NAFLD. Since NAFLD is prevalent in 25% of the general population it is more plausible to relate the occurrence of cryptogenic cirrhosis in FMF patients to NAFLD rather than to FMF. M694V mutation carriage was relatively more frequent among FMF patients with cryptogenic cirrhosis or "hepatitis". CONCLUSIONS: The literature review indicates that FMF and liver disease are not generally associated. However, carriage of M694V mutations may play a role in the pathogenesis of liver disease.PMID: 28598780 [PubMed - indexed for MEDLINE […]

  • Multiplexed Point-of-Care Testing - xPOCT.

    Related ArticlesMultiplexed Point-of-Care Testing - xPOCT. Trends Biotechnol. 2017 08;35(8):728-742 Authors: Dincer C, Bruch R, Kling A, Dittrich PS, Urban GA Abstract Multiplexed point-of-care testing (xPOCT), which is simultaneous on-site detection of different analytes from a single specimen, has recently gained increasing importance for clinical diagnostics, with emerging applications in resource-limited settings (such as in the developing world, in doctors' offices, or directly at home). Nevertheless, only single-analyte approaches are typically considered as the major paradigm in many reviews of point-of-care testing. Here, we comprehensively review the present diagnostic systems and techniques for xPOCT applications. Different multiplexing technologies (e.g., bead- or array-based systems) are considered along with their detection methods (e.g., electrochemical or optical). We also address the unmet needs and challenges of xPOCT. Finally, we critically summarize the in-field applicability and the future perspectives of the presented approaches.PMID: 28456344 [PubMed - indexed for MEDLINE […]

  • A survey of resistance to colchicine treatment for French patients with familial Mediterranean fever.

    Related ArticlesA survey of resistance to colchicine treatment for French patients with familial Mediterranean fever. Orphanet J Rare Dis. 2017 Mar 16;12(1):54 Authors: Corsia A, Georgin-Lavialle S, Hentgen V, Hachulla E, Grateau G, Faye A, Quartier P, Rossi-Semerano L, Koné-Paut I Abstract BACKGROUND: Colchicine is the standard treatment for familial Mediterranean fever (FMF), preventing attacks and inflammatory complications. True resistance is rare and yet not clearly defined. We evaluated physicians' definition of colchicine resistance and report how they manage it. PATIENTS AND METHODS: We recruited patients with a clinical diagnosis of FMF, one exon-10 Mediterranean fever (MEFV) gene mutation and considered resistant to colchicine, via networks of expert physicians. Clinical, biological characteristics and information about colchicine treatment (dose adjustment, compliance) were collected. The severity of FMF was assessed by the Tel Hashomer criteria. RESULTS: We included 51 patients, most females (55%), mean age 34 ± 23.1 years years (range 4.7-86.3). Overall, 58% (27/47) patients had homozygous M694 MEFV gene mutations. Seventeen of 42 patients (40%) declared full adherence to colchicine treatment, greater for children (48%) than adults (22%). Physicians considered colchicine resistance with > 6 attacks/year (n = 21/51, 42%), > 4 attacks in the last 6 months (n = 13/51, 26%), persistent inflammation (n = 23/51, 45%), renal amyloidosis in (n = 6/28, 22%) of adult patients and intolerance to an increase in colchicine dose (n = 10/51, 19%), and other reasons (n = 13/51, 23%), including chronic arthralgia (n = 6/51, 12%). Interleukin 1-targeting drugs represented the only alternative treatments in addition to daily colchicine. CONCLUSION: Resistance to colchicine is rare (<10% of patients) and mostly observed in severe MEFV genotypes. The main reasons for physicians assessing resistance were severe clinical symptoms, persistent subclinical inflammation, and secondary amyloidosis. Low adherence to colchicine treatment is a key component of resistance.PMID: 28302131 [PubMed - indexed for MEDLINE […]

  • Normal arterial stiffness in familial Mediterranean fever. Evidence for a possible cardiovascular protective role of colchicine.

    Related ArticlesNormal arterial stiffness in familial Mediterranean fever. Evidence for a possible cardiovascular protective role of colchicine. Clin Exp Rheumatol. 2017 Nov-Dec;35 Suppl 108(6):32-37 Authors: Kukuy O, Livneh A, Mendel L, Benor A, Giat E, Perski O, Feld O, Kassel Y, Ben-Zvi I, Lidar M, Holtzman EJ, Leiba A Abstract OBJECTIVES: Familial Mediterranean fever (FMF) is an autoinflammatory disorder with episodic and persistent inflammation, which is only partially suppressed by continuous colchicine treatment. While chronic inflammation is considered an important cardiovascular risk factor in many inflammatory disorders, its impact in FMF is still disputed. We measured arterial stiffness, a marker of atherosclerotic cardiovascular disease, in a group of FMF patients, in order to evaluate the cardiovascular consequences of inflammation in FMF and the role of colchicine in their development. METHODS: Eighty colchicine treated FMF patients, without known traditional cardiovascular risk factors, were randomly enrolled in the study. Demographic, genetic, clinical and laboratory data were retrieved from patient files and examinations. Arterial stiffness was measured using pulse wave velocity (PWV). The recorded values of PWV were compared with those of an age and blood pressure adjusted normal population, using internationally endorsed values. RESULTS: FMF patients displayed normal PWV values, with an even smaller than expected proportion of patients deviating from the 90th percentile of the reference population (5% vs. 10%, p=0.02). The lowest PWV values were recorded in patients receiving the highest dose of colchicine (≥2 mg vs. 0-1 mg, p=0.038), and in patients of North African Jewish origin, whose disease was typically more severe than that of patients of other ethnicities; both observations supporting an ameliorating colchicine effect (p=0.043). CONCLUSIONS: Though subjected to chronic inflammation, colchicine treated FMF patients have normal PWV. Our findings provide direct evidence for a cardiovascular protective role of colchicine in FMF.PMID: 28229824 [PubMed - indexed for MEDLINE […]

  • A position for tumor necrosis factor inhibitors in the management of colchicine-resistant familial Mediterranean fever?

    Related ArticlesA position for tumor necrosis factor inhibitors in the management of colchicine-resistant familial Mediterranean fever? Immunol Lett. 2016 12;180:77-78 Authors: Rigante D, Manna R PMID: 27984066 [PubMed - indexed for MEDLINE […]

  • Cytokine signatures in hereditary fever syndromes (HFS).

    Related ArticlesCytokine signatures in hereditary fever syndromes (HFS). Cytokine Growth Factor Rev. 2017 Feb;33:19-34 Authors: Ibrahim JN, Jéru I, Lecron JC, Medlej-Hashim M Abstract Hereditary fever syndromes (HFS) include a group of disorders characterized by recurrent self-limited episodes of fever accompanied by inflammatory manifestations occurring in the absence of infection or autoimmune reaction. Advances in the genetics of HFS have led to the identification of new gene families and pathways involved in the regulation of inflammation and innate immunity. The key role of several cytokine networks in the pathogenesis of HFS has been underlined by several groups, and supported by the rapid response of patients to targeted cytokine blocking therapies. This can be due to the direct effect of cytokine overproduction or to an absence of receptor antagonist resulting in dysbalance of downstream pro- and anti-inflammatory cytokine networks. The aim of this study was to present an overview and to discuss the major concepts regarding the cellular and molecular immunology of HFS, with a particular focus on their specific cytokine signatures and physiopathological implications. Based on their molecular and cellular mechanisms, HFS have been classified into intrinsic and extrinsic IL-1β activation disorders or inflammasomopathies, and protein misfolding disorders. This review integrates all recent data in an updated classification of HFS.PMID: 27916611 [PubMed - indexed for MEDLINE […]