[Developments in pyoderma gangrenosum therapy in 2015]. / Actualité sur la prise en charge du pyoderma gangrenosum en 2015.

Diagnosis of pyoderma gangrenosum in 2014 continues to be made on clinical grounds, with the main form comprising an ulcer having poorly delineated purplish edges. The diagnostic criteria have been recently modified so as to rule out differential diagnoses (10% of retrospective series of pyoderma patients). The condition is commonly associated with other diseases (75%) such as emerging endocrine diseases (36.7%), and classical gastrointestinal, rheumatological and haematological diseases. The new concepts of PAPA and PASH syndromes, belonging to the category of auto-inflammatory diseases, provide new therapeutic perspectives. Corticosteroids continue to be the first-line therapy, along with immunosuppressant drugs in the event of steroid dependence. Second-line treatments consisting biotherapies show promise and interleukin-1 inhibitors have exhibited potential against pyoderma syndrome.

[Genetic mosaicism in Systemic Auto-Inflammatory Diseases: A review of the literature]. / Mosaïcisme génétique dans les maladies auto-inflammatoires : revue de la littérature.

Systemic auto-inflammatory diseases (SAIDs) are disorders associated with deregulation of innate immunity in which patients present classically with systemic inflammatory manifestations, in particular fever, skin-mucosal rashes, arthromyalgia and abdominal pain, with an increase in blood biomarkers of inflammation. At the time of their discovery, these diseases were associated with constitutional mutations in genes encoding proteins involved in innate immunity, and it was then considered that they had to begin in childhood. This dogma of constitutional mutations in SAIDs is no longer so unquestionable, since 2005 several cases of mosaicism have been reported in the literature, initially in cryopyrinopathies, but also in other SAIDs in patients with obvious clinical phenotypes and late onset of disease expression, in particular in the VEXAS syndrome (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic Syndrome) and very recently in MEVF gene. Next-generation sequencing techniques are more sensitive than Sanger for detecting mosaicisms. So, when a clinical diagnosis seems obvious but no constitutional mutation is found by low-depth genetic analysis, it is useful to discuss with expert geneticists whether to consider another genetic approach in a child or an adult. This modifies the situations in which clinicians can evoke these diseases. This review provides an update on mosaicism in SAIDs.

[Lung involvement in autoinflammatory diseases]. / Atteinte pulmonaire dans les maladies auto-inflammatoires.

Genetic autoinflammatory diseases are now a recognized and rapidly expanding group. The lung involvement historically associated with autoinflammatory diseases is inflammatory seritis, primarily seen in familial Mediterranean fever and other interleukin-1 mediated diseases. Over the last ten years, pulmonary involvement has been the core presentation of two autoinflammatory diseases associated with constitutive type I interferon activation, i.e. SAVI and COPA syndrome. Most patients with these diseases usually develop early progression to pulmonary fibrosis, which is responsible for high rates of morbidity and mortality. Other rare autoinflammatory diseases are associated with alveolar proteinosis, particularly when related to MARS mutations. Additionally, in adults, VEXAS is frequently associated with pulmonary involvement, albeit without prognosis effect. A molecular approach to autoinflammatory diseases enables not only the definition of biomarkers for diagnosis, but also the identification of targeted treatments. Examples include JAK inhibitors in SAVI and COPA syndrome, even though this therapy does not prevent progression to pulmonary fibrosis. Another illustrative example is the efficacy of methionine supplementation in alveolar proteinosis linked to MARS mutations. Overall, in autoinflammatory diseases the lung is now emerging as a possible affected organ. Continuing discovery of new autoinflammatory diseases is likely to uncover further pathologies involving the lung. Such advances are expected to lead to the development of novel therapeutic perspectives.

French practical guidelines for the diagnosis and management of AA amyloidosis.

AA amyloidosis is secondary to the deposit of excess insoluble Serum Amyloid A (SAA) protein fibrils. AA amyloidosis complicates chronic inflammatory diseases, especially chronic inflammatory rheumatisms such as rheumatoid arthritis and spondyloarthritis; chronic infections such as tuberculosis, bronchectasia, chronic inflammatory bowel diseases such as Crohn's disease; and auto-inflammatory diseases including familial Mediterranean fever. This work consists of the French guidelines for the diagnosis workup and treatment of AA amyloidosis. We estimate in France between 500 and 700 cases in the whole French population, affecting both men and women. The most frequent organ impaired is kidney which usually manifests by oedemas of the lower extremities, proteinuria, and/or renal failure. Patients are usually tired and can display digestive features anf thyroid goiter. The diagnosis of AA amyloidosis is based on detection of amyloid deposits on a biopsy using Congo Red staining with a characteristic green birefringence in polarized light. Immunohistochemical analysis with an antibody directed against Serum Amyloid A protein is essential to confirm the diagnosis of AA amyloidosis. Peripheral inflammatory biomarkers can be measured such as C Reactive protein and SAA. We propose an algorithm to guide the etiological diagnosis of AA amyloidosis. The treatement relies on the etiologic treatment of the undelying chronic inflammatory disease to decrease and/or normalize Serum Amyloid A protein concentration in order to stabilize amyloidosis. In case of renal failure, dialysis or even a kidney transplant can be porposed. Nowadays, there is currently no specific treatment for AA amyloidosis deposits which constitutes a therapeutic challenge for the future.

[Transition from pediatric to adult care: Recommendations of the French network for autoimmune and autoinflammatory diseases (FAI2R)]. / La transition de la pédiatrie à l'âge adulte : recommandations de prise en charge de la filière des maladies auto-immunes et auto-inflammatoires rares FAI2R.

Autoimmune and autoinflammatory diseases (AIDs) are a heterogeneous group of diseases. They can occur in childhood and account for significant morbidity and mortality. Transitioning from pediatric to adult healthcare can be difficult for patients and their families. It can interfere with patient follow-up and management, and eventually lead to complications. Although recommendations exist for the successful transition of patients with chronic diseases, few are specifically adapted to children and adults with AIDs (Suris et al., 2015-Solau-Gervais, 2012). The French working group on transition of the rare autoimmune and autoinflammatory diseases presents its reflections and recommendations for a successful transition. Preparation for transition should start early. Its goals are to empower adolescents by providing them with the knowledge to manage their own care, respond appropriately to changes in their condition, and evolve within the adult healthcare system. This requires the active participation of the patient, his or her family, as well as the pediatric and adult medical teams. The transition process involves multidisciplinary care and dedicated therapeutic education programs. Finally, the identification of medical specialists by region, trained in rare AIDs and accompanied by expert patients, may improve the management of patients with rare AIDs from adolescence to adulthood.

[Clinical overview of auto-inflammatory diseases]. / Panorama des maladies auto-inflammatoires.

Monogenic auto-inflammatory diseases are characterized by genetic abnormalities coding for proteins involved in innate immunity. They were initially described in mirror with auto-immune diseases because of the absence of circulating autoantibodies. Their main feature is the presence of peripheral blood inflammation in crisis without infection. The best-known auto-inflammatory diseases are mediated by interleukines that consisted in the 4 following diseases familial Mediterranean fever, cryopyrinopathies, TNFRSF1A-related intermittent fever, and mevalonate kinase deficiency. Since 10 years, many other diseases have been discovered, especially thanks to the progress in genetics. In this review, we propose the actual panorama of the main known auto-inflammatory diseases. Some of them are recurrent fevers with crisis and remission; some others evaluate more chronically; some are associated with immunodeficiency. From a physiopathological point of view, we can separate diseases mediated by interleukine-1 and diseases mediated by interferon. Then some polygenic inflammatory diseases will be shortly described: Still disease, Schnitzler syndrome, aseptic abscesses syndrome. The diagnosis of auto-inflammatory disease is largely based on anamnesis, the presence of peripheral inflammation during attacks and genetic analysis, which are more and more performant.

[Inflammasomes in human diseases]. / Les inflammasomes et les maladies humaines.

The understanding of the innate immunity, the first line of the host defence, was significantly modified following the sequential discovery of innate immune receptors such as the Toll-like receptors (TLRs) and the NOD-like receptors (NLRs). In response to recognition of microbial patterns or danger signals, some NLRs assemble a multimolecular platform termed as the inflammasome. Inflammasome assembly leads to the activation of the proinflammatory caspase-1. Consequently, an inflammatory immune response is mounted along with a programmed cell death, called pyroptosis. This review summarizes recent advances in the knowledge of the inflammasome and its role in auto-inflammatory diseases, autoimmune diseases, and most common metabolic, cardiovascular or rheumatic diseases.