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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., (Copyright © 2022 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Familial Mediterranean fever (FMF) patients may have hepatic cytolysis, although its origin is not formally elucidated. We aimed to evaluate liver involvement in familial Mediterranean fever (FMF) using non-invasive methods. All adult FMF patients harboring two non-ambiguous mutations of the MEFV gene with hepatic cytolysis were identified in a French tertiary adult center for FMF. Liver impairment was explored with FibroMax (a non-invasive method to estimate hepatic steatosis, necrosis, inflammation and fibrosis) and liver ultrasound. Among 520 FMF adult patients, 43 had persistent hepatic cytolysis and 20 patients were included (11 women, median age at inclusion: 49.5 years). According to the FibroMax results, patients were classified as having steatosis, fibrosis, and possible or definite nonalcoholic steato-hepatitis in 10 (50%), 9 (45%) and 7 (35%) of cases, respectively. The score of steatosis did not seem associated with the usual metabolic risk factors. No significant association was found between the cumulated dose of colchicine and any of the scores included in FibroMax. In adult FMF patients with persistent hepatic cytolysis, steatosis is the first cause to consider even in the absence of usual metabolic risk factors, suggesting other mechanisms. Colchicine did not seem to be involved in this toxicity., (© 2022. The Author(s).)

Introduction: Familial Mediterranean fever (FMF) is the most frequent monogenic autoinflammatory disorder; and leads to the uncontrolled production of interleukin (IL)-1β. Multiple sclerosis (MS) is an inflammatory disease of the central nervous system; and its development seems to be partly correlated with IL-1β levels. It is hypothesized that FMF could be associated with MS. We aim to describe the features of patients displaying both diseases and to investigate the MEFV mutation rate in MS patients., Methods: Patients with definite MS were retrieved from the cohort of FMF patients in the Reference Center for Rare Auto-inflammatory Diseases and Amyloidosis (CEREMAIA). We also performed a systematic literature review of articles from PubMed that were published from 1990 to 2020., Results: Twenty-four patients were included in the case series: five patients (1.3%) from our cohort of 364 and 19 patients from the literature. The sex ratio was 2:1. The mean age at diagnosis of FMF was 19 years old; and that for MS was 29 years old. Seven studies investigating the MEFV mutation rate in MS patients were included. Three studies found a higher mutation rate in MS patients than in the control group., Conclusion: FMF and MS features were comparable to those of patients with unrelated diseases; and MEFV mutation carriage was not positively correlated with MS. However; MS prevalence in FMF patients was higher than was expected in a healthy population. To a lesser extent; FMF prevalence in MS patients was higher than expected in a healthy population and the difference might not be significant. These data suggest that FMF could be associated with MS; and further studies are needed to investigate a potential causal association., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: Familial Mediterranean Fever (FMF), the most common monogenic auto-inflammatory disease, is characterized by recurrent febrile abdominal pain. Helicobacter pylori infection (HPI), one of the most frequent infections worldwide, can mimic an FMF attack., Objectives: Identify FMF patients with HPI in a cohort of French FMF patients and the literature and identify features allowing to distinguish HPI from an FMF attack., Methods: A retrospective study of all HPI cases was performed on the cohort of FMF patients fulfilling the Livneh criteria from the French Reference Center for rare Auto-Inflammatory Diseases and Amyloidosis (CEREMAIA). A systematic literature review of HPI in FMF patients was conducted according to the PRISMA guidelines., Results: Eight French patients developed HPI, whose symptoms of epigastralgia, diarrhea, anorexia/weight loss, and nausea/vomiting differed from their typical abdominal FMF attacks. A total of 112 FMF patients with HPI have been described in the literature, including 61 adults. Diagnosis of HPI was made by gastroscopy (n = 43), labelled urea test (n = 55) or IgG serology by ELISA (n = 12). When performed, C-reactive protein was always elevated. Ten cases of interaction between colchicine and antibiotic therapy for HPI (clarithromycin (n = 9) and azithromycin (n = 1)) were reported., Conclusion: We described a total of 120 patients with typical FMF and HPI. When FMF patients develop atypical abdominal symptoms, upper gastrointestinal endoscopy with biopsies is essential to eliminate underlying HPI. Untreated HPI can lead to misdiagnosis of colchicine resistance with inappropriate prescription of an interleukin-1 inhibitor at a non-negligible cost., (© 2021 John Wiley & Sons Ltd.)

Background and Objective: Familial Mediterranean fever (FMF) is the most frequent hereditary autoinflammatory disease. Its diagnosis relies on a set of clinical criteria and a genetic confirmation on identification of biallelic pathogenic MEFV variants. MEFV encodes pyrin, an inflammasome sensor. Using a kinase inhibitor, UCN-01, we recently identified that dephosphorylation of FMF-associated pyrin mutants leads to inflammasome activation. The aim of this study was to assess whether quantifying UCN-01-mediated inflammasome activation could discriminate FMF patients from healthy donors (HD) and from patients with other inflammatory disorders (OID)., Methods: Real-time pyroptosis and IL-1β secretion were monitored in response to UCN-01 in monocytes from FMF patients (n=67), HD (n=71) and OID patients (n=40). Sensitivity and specificity of the resulting diagnostic tests were determined by receiver operating characteristic curve analyses., Results: Inflammasome monitoring in response to UCN-01 discriminates FMF patients from other individuals. Pyroptosis assessment leads to a fast FMF diagnosis while combining pyroptosis and IL-1β dosage renders UCN-01-based assays highly sensitive and specific. UCN-01-triggered monocytes responses were influenced by MEFV gene dosage and MEFV mutations in a similar way as clinical phenotypes are., Conclusions: UCN-01-based inflammasome assays could be used to rapidly diagnose FMF, with high sensitivity and specificity., Competing Interests: Competing interests: YJ, FM, AB, AM and TH are coinventors and owners of a patent 'Methods and kits for diagnosis of familial Mediterranean fever' (WO/2019/048569)., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Familial Mediterranean fever (FMF) can be complicated by AA amyloidosis (AAA), though it remains unclear why only some patients develop amyloidosis. We examined the gut microbiota composition and inflammatory markers in patients with FMF complicated or not by AAA., Methods: We analysed the gut microbiota of 34 patients with FMF without AAA, 7 patients with FMF with AAA, 19 patients with AAA of another origin, and 26 controls using 16S ribosomal RNA gene sequencing with the Illumina MiSeq platform. Associations between bacterial taxa and clinical phenotypes were evaluated using multivariate association with linear models statistical method. Blood levels of interleukin (IL)-1β, IL-6, tumour necrosis factor-α and adipokines were assessed by ELISA; indoleamine 2,3-dioxygenase (IDO) activity was determined by high-performance liquid chromatography., Results: Compared with healthy subjects, specific changes in faecal microbiota were observed in FMF and AAA groups. Several operational taxonomic units (OTUs) were associated with FMF. Moreover, two OTUs were over-represented in FMF-related AAA compared with FMF without AAA. Additionally, higher adiponectin levels and IDO activity were observed in FMF-related AAA compared with FMF without AAA (p<0.05)., Conclusion: The presence of specific changes in faecal microbiota in FMF and in FMF-related AAA suggests that intestinal microorganisms may play a role in the pathogenesis of these diseases. These findings may offer an opportunity to use techniques for gut microbiota manipulation., Competing Interests: Competing interests: None., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)