French protocol for the diagnosis and management of familial Mediterranean fever.

Familial Mediterranean fever is the most common monogenic auto-inflammatory disease in the world. It mainly affects people originating from the Mediterranean region. The mutated gene is MEFV, which codes for pyrin. Transmission is autosomal recessive. Patients present with recurrent attacks of fever since childhood associated with abdominal and/or thoracic pain lasting an average of 2-3days and a biological inflammatory syndrome. Other symptoms include arthralgia or arthritis in large joints such as the knees and ankles, myalgia in the lower limbs and pseudo-erysipelas in the ankles. The most serious complication is inflammatory amyloidosis, which can lead to kidney failure. Treatment is based on colchicine, which helps to prevent flares and the onset of renal amyloidosis. This paper proposes national guidelines for the diagnosis, management and follow-up of familial Mediterranean fever in France, where we estimate there are between 5000 and 10,000 patients with the disease at all stages of life. The diagnosis is suspected on the basis of clinical and anamnestic factors and confirmed by genetic analysis. These guidelines also suggest a "treat-to-target" approach to disease management, particularly in case of suspected colchicine resistance - a very rare situation that should remain a diagnosis of elimination, especially after colchicine compliance has been verified. Two special situations are also addressed in these guidelines: kidney failure and pregnancy.

[Complement inhibitors: A global point of view]. / Les inhibiteurs du complément : une vue d'ensemble.

Innate immunity, and more specifically the complement system, has arised renewed interest in the medical field in recent years. Many innovative complement-inhibiting drugs have appeared, acting at various levels of the complement cascade. These drugs have made it possible to transform poor prognosis of certain diseases. Many of them are currently being tested in clinical trials for various indications. Many questions appear about their optimal use and their future indications. This article recalls the fundamental role of the complement system in the human organism. It then discusses the diseases in which the complement is involved on the pathophysiological level. The third part details the different classes of complement inhibitors and briefly recalls the indications for which these treatments seem the most promising. Finally, we end with a discussion that highlights the different aspects and questions induced by these new treatments.

Is neutrophilic dermatosis a manifestation of familial Mediterranean fever?

Objectives: Familial Mediterranean fever (FMF) is the most frequent monogenic autoinflammatory disease. It is associated with MEFV mutations. Its main features are recurrent episodes of fever and serositis. Patients can display dermatological manifestations such as erysipelas-like erythema, generally considered as a neutrophilic dermatosis (ND). It has been suggested that FMF can be associated with other types of ND. Our aim was to perform a systematic review of the literature to assess the link between ND and FMF.Method: A systematic review of the literature was performed using MEDLINE from 1946 to 2018. Three independent investigators identified reports of non-erysipelas-like erythema neutrophilic dermatosis (NEND) associated with FMF, selected the criteria to establish the diagnosis of FMF and ND, and evaluated the link between the two conditions. FMF-associated NEND was supported by confirmation of both diagnoses and exclusion of other causes of ND.Results: Eighteen articles were selected. Nine articles reported FMF patients with the following NEND: neutrophilic panniculitis (n = 4), Sweet syndrome (n = 6), and pyoderma gangrenosum (n = 1). None of these cases was supported by histological confirmation, fulfilled diagnostic criteria for definitive or probable FMF, or confirmed the exclusion of all the most frequent diseases associated with NEND. As a result, there is insufficient evidence to support a potential relationship between NEND and FMF.Conclusions: The association between FMF and NEND remains unclear. In FMF patients with NEND, every differential diagnosis and alternative cause of NEND should be excluded before drawing any conclusions about a potential causal relationship.

[Adult-onset Still's disease complications]. / Complications de la maladie de Still de l'adulte.

Adult-onset Still's disease (AOSD), first described in 1971 by Bywaters, is a rare systemic auto-inflammatory disorder of unknown etiology, characterized by a symptomatic triad associating prolonged fever, polyarthritis and rash. The management of this disease has significantly improved since its first description, and, although the overall prognosis of the AOSD is good, with a low attributable mortality, below 3% (but up to 18% depending on the series), some rare complications are still possible, can be life-threatening and change the prognosis of the disease. A literature search was performed to review AOSD's complications: reactive hemophagocytic lymphohystiocytosis, coagulation disorders, fulminant hepatitis, cardiovascular (pericarditis, myocarditis, HTAP) or pulmonary complications, neurologic, renal complications, and AA amyloidosis. For most of AOSD-related complications, corticosteroids remain the first-line treatment, in association with supportive care measures in case of severe complications. In case of inadequate response, multidisciplinary care with concil from a referral center is advised, and IL-1 or IL-6 blockers, but also ciclosporine, are the molecule to use in second intention.

AA amyloidosis secondary to adult onset Still's disease: About 19 cases.

OBJECTIVE: Adult onset Still's disease (AOSD) is an inflammatory disorder characterized by high spiking fever, evanescent rash, polyarthritis, and many other systemic manifestations. Recurrent or persistent disease can lead to AA amyloidosis (AAA). Our objectives were to present 3 French cases and perform a systematic review of the literature, in order to determine the prevalence, characteristics, predisposing factors, and therapeutic response of AOSD-related AAA. METHODS: A systematic literature review was performed by searching MEDLINE from 1971 to 2018. Two independent investigators selected reports of AAA complicating AOSD. New French cases were identified with the help of the Reference Center for rare Auto-Inflammatory Diseases and Amyloidosis (CEREMAIA). Patients with juvenile idiopathic arthritis were excluded. RESULTS: The prevalence of AAA in AOSD was 0.88% (95%CI [0.49-1.28]) based on 45 articles. In addition to 3 new cases from the CEREMAIA, 16 patients were assessed for clinical presentation, risk factors, and therapeutic response of AOSD-related AAA. Mean age at AOSD onset was 29.6 ±â€¯12.6 years, with a mean delay before AAA diagnosis of 16.75±5.8 years. Renal involvement was the most common manifestation of AAA. The majority of patients presented active AOSD at AAA diagnosis. Various treatments of AOSD-related AAA were attempted including corticosteroids and biotherapies. CONCLUSION: AAA is a rare and severe complication that may occur during the course of uncontrolled active AOSD. It could be prevented by early diagnosis and better control of AOSD, with more frequent use of biotherapies.

[Familial Mediterranean fever]. / La fièvre méditerranéenne familiale.

Familial Mediterranean Fever (FMF) is the most frequent monogenic auto-inflammatory disease. FMF is an autosomal recessive disease, which affects populations from Mediterranean origin and is associated with MEFV gene mutations encoding for the protein pyrin. Pyrin activation enhances the secretion of interleukin 1 by myelo-monocytic cells. Main features of the disease are acute attacks of serositis mainly located on the abdomen, less frequently on chest and joints, accompanied by fever and biological inflammatory markers elevation. Usually attacks last 1 to 3 days and spontaneously stop. A daily oral colchicine intake of 1 to 2mg/day is able to prevent attack's occurrence, frequency, intensity and duration among most patients. Colchicine is also able to prevent the development of inflammatory amyloidosis, the most severe complication of FMF. This state of the art article will focus on the diagnosis of FMF, the treatment and an update on the pathophysiology including the recent described dominant form of MEFV-associated new auto-inflammatory diseases.

Subchondral tibial bone texture analysis predicts knee osteoarthritis progression: data from the Osteoarthritis Initiative: Tibial bone texture & knee OA progression.

OBJECTIVES: To examine whether trabecular bone texture (TBT) parameters assessed on computed radiographs could predict knee osteoarthritis (OA) progression. METHODS: This study was performed using data from the Osteoarthritis Initiative (OAI). 1647 knees in 1124 patients had bilateral fixed flexion radiographs acquired 48 months apart. Images were semi-automatically segmented to extract a patchwork of regions of interest (ROI). A fractal texture analysis was performed using different methods. OA progression was defined as an increase in the joint space narrowing (JSN) over 48 months. The predictive ability of TBT was evaluated using logistic regression and receiver operating characteristic (ROC) curve. An optimization method for features selection was used to reduce the size of models and assess the impact of each ROI. RESULTS: Fractal dimensions (FD's) were predictive of the JSN progression for each method tested with an area under the ROC curve (AUC) up to 0.71. Baseline JSN grade was not correlated with TBT parameters (R < 0.21) but had the same predictive capacity (AUC 0.71). The most predictive model included the clinical covariates (age, gender, body mass index (BMI)), JSN and TBT parameters (AUC 0.77). From a statistical point of view we found higher differences in TBT parameters computed in medial ROI between progressors and non-progressors. However, the integration of TBT results from the whole patchwork including the lateral ROIs in the model provided the best predictive model. CONCLUSIONS: Our findings indicate that TBT parameters assessed in different locations in the joint provided a good predictive ability to detect knee OA progression.

Developing and validating a practical decision support tool (DST) for biomass selection on marginal land.

Marginal, often contaminated, sites exist in large areas across the world as a result of historic activities such as industry, transportation and mineral extraction. Remediation, or other improvements, of these sites is typically only considered for sites with high exploitation pressure and those posing the highest risks to human health or the environment. At the same time there is increasing competition for land resources for different needs such as biofuel production. Potentially some of this land requirement could be met by production of biomass on brownfield or other marginal land, thereby improving the land while applying the crop cultivation as part of an integrated management strategy. The design and decision making for such a strategy will be site specific. A decision support framework, the Rejuvenate DST (decision support tool) has been developed with the aim of supporting such site specific decision making. This tool is presented here, and has been tested by applying it to a number of case study sites. The consequent SWOT (strength, weakness, opportunities and threats) analysis is discussed and evaluated. The DST was found to be systematic, transparent, and applicable for diverse sites in France, Romania and Sweden, in addition to the sites to which it was applied through its development. The DST is regarded as especially useful if applied as a checklist in an iterative way throughout the decision process, from identifying potential crops to identifying knowledge gaps, working/non-working management strategies and potential risks. The DST also provides a structure promoting effective stakeholder engagement.

[Repositioning accuracy of cerebral fractionated stereotactic radiotherapy using CT scanning]. / Evaluation par tomodensitométrie du repositionnement en radiothérapie stéréotaxique fractionnée cérébrale.

PURPOSE: To evaluate the accuracy of patient repositioning in fractionated cerebral stereotactic radiotherapy using a Brain Lab stereotactic cranial mask in conjunction with standard dental fixation. PATIENTS AND METHODS: Fifty planning and checking CT scans were performed in 25 patients. The check CT scan was performed before or after one of the three sessions of treatment. Coregistration to the planning CT scan was used to assess alignment of the isocentre to the reference markers. The relative position of the PTV with regard to isocentre allowed us to determine its total displacement (3D vector). RESULTS: Mean isocentre translations (+/-SD) taking into account direction were -0.01+/-0.7, -0.2+/-1.3 and 0.07+/-0.5mm in mediolateral, craniocaudal and anteroposterior directions respectively. Mean rotations (+/- SD) were -0.02+/-0.6, -0.08+/-0.3 and -0.1+/-0.3 degree in mediolateral, craniocaudal and anteroposterior axes respectively. Mean overall PTV displacement was 1.8+/-1.5mm. PTV displacement was smaller than 2 and 3mm in 19/25 and 23/25 patients respectively. CONCLUSION: The accuracy of patient positioning using a stereotactic cranial mask system is similar to those reported in the literature and shows a satisfactory reproducibility with a standard dental fixation.