Familial Mediterranean fever (FMF) is an interleukin-1 (IL-1)-driven autoinflammatory disease in which pericarditis, occasionally complicated by cardiac tamponade, is a recognized manifestation, whereas hypereosinophilia is not. We report a woman in her thirties with FMF (homozygous MEFV M694V mutation) receiving colchicine 2.5 mg/day, admitted in the third trimester of pregnancy for dyspnea, fever, and cough. She had blood hypereosinophilia (2.9 G/L), bilateral lung consolidation with bronchoalveolar lavage eosinophilia (46%) and myopericarditis. Cardiac tamponade required emergency pericardiocentesis and cesarean section, with favorable maternal and neonatal outcomes; pericardial fluid contained more than 90% eosinophils. Infectious, autoimmune, drug-induced, and clonal causes were excluded. High-dose corticosteroids only transiently reduced the eosinophil count, which rebounded, while C-reactive protein remained elevated. Both parameters normalized after anakinra was started, allowing corticosteroid withdrawal, with sustained remission at 36 months. Whether hypereosinophilia was a manifestation of FMF or a coincidental association remains undetermined. IL-1 blockade nonetheless controlled both the serositis and the eosinophilia, and may limit corticosteroid exposure.

Autoinflammatory diseases are characterized by dysregulation of the innate immune system. This article provides an updated overview of autoinflammatory diseases with gastrointestinal manifestations and outlines the clinical situations in which gastroenterologists should consider these conditions. The most prevalent form worldwide is familial Mediterranean fever (FMF), which is associated with mutations in the MEFV (MEditerranean FeVer) gene and presents with recurrent episodes of serositis, primarily peritonitis, accompanied by systemic inflammation. From a biological standpoint, a peripheral inflammatory syndrome is typically observed during acute attacks; however, in some cases inflammation may persist chronically. At the molecular level, these diseases involve numerous genes encoding proteins that participate in the activation or regulation of inflammatory pathways within innate immune cells. Initially, four monogenic disorders were described FMF, TNF receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency (MKD), and cryopyrin-associated periodic syndromes (CAPS) collectively referred to as the four historical autoinflammatory diseases. Each year, new monogenic autoinflammatory diseases are identified thanks to rapid advances in genetic sequencing technologies. The recent identification of somatic forms of monogenic diseases, including certain cryopyrinopathies and, in 2020, VEXAS syndrome, has added a new level of complexity to the field.

OBJECTIVES:AA amyloidosis (AAA) is a complication of chronic inflammation whose burden is expected to decrease in the era of biological therapies. We assessed the prevalence, clinical and laboratory manifestations, management and evolution of AAA in patients with inflammatory joint diseases (IJDs). METHODS:We retrospectively assessed adults followed from 2008 to 2025 in 2 French tertiary university hospitals. AAA had to be histologically confirmed and related to one of the following IJDs: rheumatoid arthritis, spondylarthritis, juvenile idiopathic arthritis, undifferentiated arthritis or gout. RESULTS:The prevalence of rheumatoid arthritis- and spondylarthritis-related AAA was low, estimated at 0.6‰ and 0.5‰, respectively. We identified 15 patients with IJD-related AAA: 5 rheumatoid arthritis, 4 spondylarthritis, 2 juvenile idiopathic arthritis, 3 undifferentiated arthritis and 1 gout. Ten (66.7%) patients were from developing countries. All patients experienced delays in diagnosis and treatment. At AAA diagnosis, most patients (80%) were not receiving any treatment for IJD. AAA clinical manifestations were mainly renal and digestive; the median (interquartile range) C-reactive protein level was 41.5 (16.8-59.5) mg/L, serum amyloid A level 31 (13-44) mg/L and proteinuria/creatinuria ratio 3.5 (1.3-5.2) g/mmol. Biological disease-modifying anti-rheumatic drugs were started in 14 patients (1 patient lost to follow-up) and resulted in clinically inactive disease in 57.2%; normal C-reactive protein and serum amyloid A and proteinuria negativity in 71.4%. CONCLUSION:In the last 2 decades, AAA occurred in only patients with IJDs who experienced long diagnostic and therapeutic delays, mainly related to country of origin and difficulties in access to care.

BACKGROUND:AA amyloidosis (AAA) remains a life-threatening yet largely preventable complication of monogenic autoinflammatory diseases (AIDs). METHODS:We retrospectively described patients with AAA secondary to one of the four historical monogenic AIDs (familial Mediterranean fever [FMF], cryopyrin-associated periodic syndrome [CAPS], mevalonate kinase deficiency [MKD] and tumour necrosis factor receptor-associated periodic syndrome [TRAPS]) followed at the French National Referral Centre for Monogenic AIDs and Inflammatory Amyloidosis (2012-2025). RESULTS:Among 181 patients followed for AAA, 50 (28%) had one of the four monogenic AIDs (FMF n = 41, CAPS n = 4, MKD n = 3, TRAPS n = 2), corresponding to an overall prevalence of 5% among all patients with monogenic AIDs. AAA preceded the diagnosis of the underlying AID in 40% of patients, particularly those with non-FMF diseases. Disease burden remained high, with 46% of patients requiring kidney transplantation, whereas mortality reached 26% during follow-up. CONCLUSION:AAA continues to reflect delayed diagnosis, highlighting the need for increased awareness among adult healthcare providers, systematic genetic evaluation of unexplained AAA and early inflammatory control.

ABSTRACTBackgroundFamilial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease, associated with MEFV mutations. FMF patients can experience liver involvement, potentially leading to cirrhosis.ObjectivesThis study aimed to evaluate liver involvement in FMF patients at a French tertiary centre for adult FMF.MethodsWe conducted an observational study with FMF patients displaying 2 pathogenic MEFV mutations at the National Reference Center for Autoinflammatory Diseases and Inflammatory Amyloidosis (CEREMAIA) in Paris and included in the JIR cohort. MEFV heterozygous patients and those with other liver disease causes were excluded.ResultsAmong 533 FMF patients 12.4% had chronic liver abnormalities, with 30% who developed cirrhosis 54 years [36–57] in median after disease onset. Forty‐seven per cent were colchicine resistant, and 41% received interleukin‐1 inhibitors. Cirrhotic patients experienced delayed hepatopathy diagnosis, prolonged FMF diagnosis delay and late‐onset treatment initiation compared to those with only liver function test abnormalities. Colchicine resistance and interleukin‐1 inhibitor use were more common in cirrhotic patients. Body mass index and AA amyloidosis rates did not differ significantly between groups. Twenty‐one patients had undergone liver biopsies including 14 cirrhotic patients revealing steatohepatitis in 12 cases and probable steatohepatitis in 4. Other lesions, like iron overload and sinusoidal dilatation, were sporadically observed.ConclusionFMF patients are at risk of chronic liver disease. Regular liver function monitoring is crucial, particularly in case of persistent inflammation, due to the risk of progression to cirrhosis and its associated morbidity and mortality.

Systemic autoinflammatory diseases (SAIDs) are associated with a dysregulation of innate immunity leading to recurrent or chronic inflammation. There are both well-characterized monogenic forms, such as familial Mediterranean fever, cryopyrinopathies and VEXAS syndrome, and multifactorial forms defined by classification criteria, such as Still's disease, Schnitzler syndrome and SITRAME. However, a significant proportion of patients, estimated at up to 73% in some series, present with an autoinflammatory phenotype without any identified pathogenic variant or established diagnosis based on classification criteria. These situations are grouped under the term undifferentiated systemic autoinflammatory diseases (USAID). In adults, the most common manifestations are recurrent fever, fatigue, myalgia, arthralgia, cutaneomucous and digestive features, ENT or ocular involvement. Clinical heterogeneity contributes to delayed diagnosis, which can take several years. Diagnosis is based on repeated documentation of a biological inflammatory syndrome, the progression of symptoms over at least six months, the exclusion of common differential diagnoses (infections, cancers, haematological disorders or autoimmune diseases) and the absence of criteria allowing to classify the patient to a defined entity. Investigations include repeated biological tests, screening for immune deficiencies or autoantibodies, and sometimes genetic testing to detect monogenic diseases with either germinal or somatic variants. In the absence of specific criteria, response to treatments targeting innate immunity, such as colchicine or cytokine inhibitors (IL-1, IL-6, TNF, JAK), may confirm the diagnosis. USAID in adults is an emerging entity, on the borderline between monogenic and multifactorial diseases, the recognition of which is essential to reduce diagnostic uncertainty and adapt management.

Les maladies auto-inflammatoires systémiques (MAIS) sont associées à une dérégulation de l’immunité innée qui entraîne une inflammation récurrente ou chronique. On distingue parmi les MAIS des formes monogéniques bien caractérisées, comme la fièvre Méditerranéenne familiale, les cryopyrinopathies ou le syndrome VEXAS ; et des formes multifactorielles définies par des critères de classification, telles que la maladie de Still, le syndrome de Schnitzler ou le SITRAME. Toutefois, une proportion importante de patients, estimée jusqu’à 73 % dans certaines séries, présente un phénotype auto-inflammatoire sans variant pathogène identifié et ne répondant pas à des critères de classification. On parle alors de maladies auto-inflammatoires systémiques indifférenciées (MAISI) ou undifferentiated systemic autoinflammatory diseases (USAID). Chez l’adulte, les manifestations les plus fréquentes des MAISI sont la fièvre récurrente, la fatigue, les myalgies, les arthralgies, les éruptions cutanéomuqueuses, les atteintes digestives ou encore ORL ou oculaires. L’hétérogénéité clinique contribue au retard du diagnostic, pouvant aller jusqu’à plusieurs années. Le diagnostic de MAISI repose sur la documentation répétée d’un syndrome inflammatoire biologique, l’évolution des symptômes depuis au moins six mois, l’exclusion des diagnostics différentiels fréquents (infections, cancers, hémopathies ou maladies auto-immunes) et l’absence de critères de classification pour une entité définie. Les explorations associent des bilans biologiques répétés, la recherche de déficits immunitaires ou d’auto-anticorps ; parfois des analyses génétiques pour dépister des formes monogéniques germinales ou somatiques. En l’absence de critères spécifiques, la réponse aux traitements ciblant l’immunité innée, comme la colchicine ou les inhibiteurs de cytokines pro-inflammatoires (IL-1, IL-6, TNF, JAK), peut conforter le diagnostic. Les MAISI de l’adulte constituent une entité émergente, à la frontière entre les maladies monogéniques et multifactorielles, dont la reconnaissance est essentielle pour réduire l’errance diagnostique et optimiser la prise en charge.

Auto-inflammatory diseases (AIDs) are characterized by excessive activation of innate immunity. Current biomarkers, such as C-reactive protein (CRP) and serum Amyloid A (SAA), are not disease-specific and cannot reflect disease severity. Interleukin-18 (IL-18), a pro-inflammatory cytokine of the IL-1 superfamily, has been recently studied as, biomarker for AIDs; This study aims to evaluate total serum IL-18 levels in a large cohort of AID patients from the adult French national reference center for AID. We conducted a retrospective analysis of 708 IL-18 measurements from 516 patients. The highest IL-18 levels were observed in diseases involving the pyrin inflammasome, such as Familial Mediterranean fever, mevalonate kinase deficiency, CDC42-associated AID and PSTPIP1-associated AID. Receiver operating characteristic (ROC) curve analysis demonstrated an AUC of 0.87 for IL-18, with a sensitivity of 83.4 % and specificity of 76.2 % at a cut-off value of 412 pg/mL, in differentiating pyrin inflammasome-related diseases from other monogenic inflammatory diseases. Our findings suggest the utility of total serum IL-18 as a diagnostic tool, particularly for pyrin inflammasome-related AIDs, that could in the future help to personalized treatment strategies.