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.

Syntheses, crystal structures, Hirshfeld surface analyses and energy frameworks of two 4-amino-anti-pyrine Schiff base compounds: (E)-4-{[4-(di-ethyl-amino)-benzyl-idene]amino}-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one and (E)-4-[(4-fluoro-benzyl-idene)amino]-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one.

The title Schiff base compounds, C22H26N4O (I) and C18H16FN3O (II), were each synthesized by a single-step condensation reaction. The substituted benzyl-idene ring is inclined to the pyrazole ring mean planes by 22.92 (7)° in I and 12.70 (9)° in II. The phenyl ring of the 4-amino-anti-pyrine unit is inclined to the pyrazole ring mean plane by 54.87 (7)° in I and by 60.44 (8)° in II. In the crystal of I, the mol-ecules are linked by C-H⋯O hydrogen bonds and C-H⋯π inter-actions to form layers lying parallel to (001). In the crystal of II, the mol-ecules are linked by C-H⋯O and C-H⋯F hydrogen bonds and C-H⋯π inter-actions, thereby forming layers lying parallel to (010). Hirshfeld surface analysis was employed to further qu-antify the inter-atomic inter-actions in the crystals of both compounds.

Synthesis and structure of 4-{[(E)-(7-meth-oxy-1,3-benzodioxol-5-yl)methyl-idene]amino}-1,5-dimethyl-2-phenyl-2,3-di-hydro-1H-pyrazol-3-one.

In the title compound, C20H19N3O4, the dihedral angles between the central pyrazole ring and the pendant phenyl and substituted benzene rings are 50.95 (8) and 3.25 (12)°, respectively, and an intra-molecular C-H⋯O link generates an S(6) ring. The benzodioxolyl ring adopts a shallow envelope conformation with the methyl-ene C atom as the flap. In the crystal, the mol-ecules are linked by non-classical C-H⋯O inter-actions, which generate a three-dimensional network. Solvent-accessible voids run down the c-axis direction and the residual electron density in these voids was modelled during the refinement process using the SQUEEZE algorithm [Spek (2015 ▸). Acta Cryst. C71, 9-18] within the structural checking program PLATON.

[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.

[Interleukin-1, inflammasome and autoinflammatory diseases]. / Interleukine-1, inflammasome et maladies auto-inflammatoires.

Interleukin-1 is a major cytokine of innate immunity and inflammation. It exerts various systemic effects during the inflammatory response, such as fever induction, thrombopoiesis and granulopoiesis, or leukocyte recruitment. Its involvement has been demonstrated in many inflammatory-mediated diseases, such as diabetes or gout. Moreover, interleukin-1 plays a pivotal role in some autoinflammatory diseases, such as cryopyrinopathies or familial Mediterranean fever. In these diseases, a constitutional defect of the inflammasome, a protein complex responsible for the activation of interleukin-1, explains the hypersecretion of interleukin-1. Other autoinflammatory diseases have a more complex pathophysiology involving deregulation of the interleukin-1 pathway, upstream or downstream of the inflammasome, or through more complex mechanisms. In this review, we are detailing the synthesis, the activation, the signalling, and the regulation of interleukin-1. We then describe the autoinflammatory diseases or related-diseases where the pathological role of interleukin-1 has been demonstrated.

Intracellular survival of Burkholderia cepacia complex in phagocytic cells.

Burkholderia cepacia complex (Bcc) species are a group of Gram-negative opportunistic pathogens that infect the airways of cystic fibrosis patients, and occasionally they infect other immunocompromised patients. Bcc bacteria display high-level multidrug resistance and chronically persist in the infected host while eliciting robust inflammatory responses. Studies using macrophages, neutrophils, and dendritic cells, combined with advances in the genetic manipulation of these bacteria, have increased our understanding of the molecular mechanisms of virulence in these pathogens and the molecular details of cell-host responses triggering inflammation. This article discusses our current view of the intracellular survival of Burkholderia cenocepacia within macrophages.