EULAR recommendations for the management of familial Mediterranean fever

Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease, but many rheumatologists are not well acquainted with its management. The objective of this report is to produce evidence-based recommendations to guide rheumatologists and other health professionals in the treatment and follow-up of patients with FMF. A multidisciplinary panel, including rheumatologists, internists, paediatricians, a nurse, a methodologist and a patient representative, was assembled. Panellists came from the Eastern Mediterranean area, Europe and North America. A preliminary systematic literature search on the pharmacological treatment of FMF was performed following which the expert group convened to define aims, scope and users of the guidelines and established the need for additional reviews on controversial topics. In a second meeting, recommendations were discussed and refined in light of available evidence. Finally, agreement with the recommendations was obtained from a larger group of experts through a Delphi survey. The level of evidence (LoE) and grade of recommendation (GR) were then incorporated. The final document comprises 18 recommendations, each presented with its degree of agreement (0-10), LoE, GR and rationale. The degree of agreement was greater than 7/10 in all instances. The more controversial statements were those related to follow-up and dose change, for which supporting evidence is limited. A set of widely accepted recommendations for the treatment and monitoring of FMF is presented, supported by the best available evidence and expert opinion. It is believed that these recommendations will be useful in guiding physicians in the care of patients with FMF

Recommendations for the management of autoinflammatory diseases.

Autoinflammatory diseases are characterised by fever and systemic inflammation, with potentially serious complications. Owing to the rarity of these diseases, evidence-based guidelines are lacking. In 2012, the European project Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) was launched to optimise and disseminate regimens for the management of children and young adults with rheumatic diseases, facilitating the clinical practice of paediatricians and (paediatric) rheumatologists. One of the aims of SHARE was to provide evidence-based recommendations for the management of the autoinflammatory diseases cryopyrin-associated periodic syndromes (CAPS), tumour necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) and mevalonate kinase deficiency (MKD). These recommendations were developed using the European League Against Rheumatism standard operating procedure. An expert committee of paediatric and adult rheumatologists was convened. Recommendations derived from the systematic literature review were evaluated by an online survey and subsequently discussed at a consensus meeting using Nominal Group Technique. Recommendations were accepted if more than 80% agreement was reached. In total, four overarching principles, 20 recommendations on therapy and 14 recommendations on monitoring were accepted with ≥ 80% agreement among the experts. Topics included (but were not limited to) validated disease activity scores, therapy and items to assess in monitoring of a patient. By developing these recommendations, we aim to optimise the management of patients with CAPS, TRAPS and MKD

Analysis of MEFV exon methylation and expression patterns in familial Mediterranean fever

<p>Abstract</p> <p>Background</p> <p>MEFV mutations and decreased expression level of the gene are related to FMF pathology. DNA methylation at CpG islands is a well-known mechanism for transcriptional silencing. MEFV has a CpG island, spanning a part of the first intron and the whole of the second exon of the gene covering 998 bp region. Here, we tested the hypothesis that the MEFV transcript level in FMF patients correlates with its methylation level, and methylation, by allowing transcription silencing, has a role in FMF ethiopathogenesis.</p> <p>Methods</p> <p>The study group was composed of pediatric FMF patients (N = 51) and age-gender matched healthy controls (N = 21). The relative expression level of MEFV was assessed via quantitative real-time PCR (qRT-PCR) and bisulfite sequencing (BS) was performed to analyse the methylation level quantitatively.</p> <p>Results</p> <p>MEFV expression in FMF patients were decreased compared to healthy controls (<it>P </it>= 0.031). Methylation level of exon 2 of MEFV was found to be slightly higher in FMF patients compared to healthy controls (76% versus 74%) (<it>P </it>= 0.049). The expression level of the MEFV was negatively correlated with the methylation level of the CpG island in both FMF and healthy controls groups (cor = -0.29, <it>P </it>= 0.041) but more so in the FMF only group (cor = -0.36, <it>P </it>= 0.035).</p> <p>Conclusions</p> <p>In this study, the relation between reduced MEFV expression level and FMF was confirmed. Observed slight increase in methylation in FMF patients, and correlation of methylation with expression might be indicative of its role in FMF, however a larger dataset is needed to confirm our preliminary findings.</p

Development of normative data for cylindrical grasp pressure

Normative data of grasp strength (GS) are commonly used in working and clinical environments. Squeezing two parallel bars of a handgrip instrument is a common method to measure GS. These instruments require the use of hook grasp position which differentiates from the other types of power grasp in terms of inclusion of the thumb. Therefore, strength performance measured with these types of dynamometers cannot be generalizable to the other types of power grasp. Although several studies have been conducted to form normative data of hook and spherical grasp strengths, a satisfactory cylindrical grasp strength norm has not been reported yet. The measurement of grasp pressure (GP) is another way of establishing the grasping capabilities of the hand and the preferred method for fragile and weak hands. The purposes of the study were to develop normative data of cylindrical GP in a healthy population and to analyze the changes in the means according to physical demands of the subjects' jobs. 770 healthy subjects (382 females, 388 males) were found to be eligible to participate in the study. A custom-made adapted sphygmomanometer having a cylindrical air-filled bag was used to measure GP. Occupational categories of the subjects were determined based on the classification in the Dictionary of Occupational Titles. The subjects were accommodated to 12 age groups per gender of five-year intervals. The mean GP of the male subjects were higher than those of female subjects in each age group. There were significant differences between the dominant and non-dominant hands in both sexes. Subjects older than 70 years achieved the lowest values. The changes of the means over age were in compliance with the curvilinear function. Only age factor was found to be resulted in significant differences in GP means at both hands of the subjects. The minimum GP means were in the "sedentary" category at both sexes (F: 225, M: 315 mmHg in the dominant hands). Male subjects in the "very heavy" category produced the highest test means (M: 371 mmHg). Further analysis on 52 male subjects demonstrated that hand length, hand circumference and palm length had the highest correlations with GP scores in sequence

Effects of serial casting in the treatment of flexion contractures of proximal interphalangeal joints in patients with rheumatoid arthritis and juvenile idiopathic arthritis: A retrospective study

Aim: To analyze the effects of serial casting (SC) in the treatment of proximal interphalangeal (PIP) joint flexion contractures in patients with rheumatoid arthritis and juvenile idiopathic arthritis

Canakinumab for the treatment of familial Mediterranean fever

Introduction: Familial Mediterranean fever (FMF) is the most frequent of all hereditary autoinflammatory syndromes. It is characterized by recurrent attacks of fever and serositis. If not treated it may be complicated with AA amyloidosis. It is caused by mutations in the MEFV gene that encodes pyrin which is involved in the regulation of IL-1. The mainstay of treatment is colchicine, however a subset of patients requires an alternative treatment either due to inadequate response or intolerance. The accumulating data indicates that anti IL-1 drugs are effective in treating colchicine resistant FMF cases and improving their quality of life.Areas covered: This review focuses on canakinumab, a fully human anti IL-1 antibody, treatment in FMF. The data obtained from case reports, case series, two Phase II studies and an ongoing double-blind, randomized, placebo controlled Phase III trial are analyzed. Efficacy and safety profiles of canakinumab are discussed.Expert commentary: Canakinumab became the first approved therapy by the Food and Drug Administration for FMF very recently, which highlights its importance as the alternative treatment in FMF