An update on autoinflammatory diseases

First author: S. Georgin-Lavialle

Abstract:

Autoinflammatory diseases (AIDs) are defined as disorders of innate immunity. They were initially defined in opposition to autoimmune diseases, due to the absence of involvement of the adaptive immune system and circulating autoantibodies. The 4 IADs first described are known as the “historic” IADs and include: familial Mediterranean fever (associated with mutations in the MEFV gene), cryopyrinopathies (associated with mutations in NLRP3), tumor necrosis factor receptor-associated periodic syndrome (associated with mutations in TNFRSF1A) and mevalonate kinase deficiency (associated with mutations in MVK). Over the past 10 years, more than 50 new monogenic IBDs have been discovered thanks to advances in genetics. Diagnosis is facilitated by personal and family history-taking and detailed analysis of the signs and symptoms associated with febrile attacks, which must be associated with the presence of elevated blood biomarkers of inflammation. Increasingly powerful genetic analysis techniques can help refine the diagnosis. This chapter describes the main types of IJD, and helps to guide the clinician in the suspicion and diagnosis of IJD.

MAi en français.pdf

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Break down the barriers of auto-inflammation:How to deal with a monogenic auto-inflammatorydisease and immuno-haematological features in 2022?

First author : Hélène Vergneault

Review: Immunology

Link to article: DOI: 10.1111/imm.13579

Principales caractéristiques immuno-hématologiques en fonction du principal mécanisme physiopathologique impliqué.

Abstract:

In the past few years, the spectrum of monogenic systemic auto-inflammatory diseases (MSAID) has widely expanded beyond the typical recurrent fever. Immunohaematological features, as cytopenias, hypogammaglobulinemia, hypereosinophilia,lymphoproliferation and immunodeficiency, have been described in association of several MSAID. The objective of this review was to describe these particular MSAID. MSAID must be suspected in front of immuno-haematological features associated with non-infectious recurrent fever, chronic systemic inflammation, inflammatory cutaneous manifestations, arthritis or inflammatory bowel disease. Genes and cellular mechanisms involved are various but some of them are of special interest. Defects in actine regulation pathway are notably associated with cytopenia and immune deficiency. Because of their frequency, ADA2 deficiency and Vacuoles, E1-Enzyme, X-linked, auto-inflammatory, Somatic (VEXAS) syndrome deserve to be noticed. ADA2 deficiency results in polyarteritis nodosalike presentation with a wide panel of manifestations including cytopenia(s), lymphoproliferation and immune deficiency. Neutrophilic dermatosis or chondritis associated with macrocytic anaemia or myelodysplasia should lead to screen for VEXAS. Of note, most of MSAID are associated with inflammatory anaemia. We proposed here a clinical and pragmatic approach of MSAID associated with immuno-haematological features.

Vergneault - Break down the barriers of auto‐inflammation How to deal with a monogenic AI.

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Characteristics of familial Mediterranean fever after 65 years of age

First author: François Rodrigues et al.

Link to article: https://doi.org/10.1016/j.ejim.2024.10.010

              Familial Mediterranean Fever (FMF) is an autosomal recessive disease caused by mutations in MEFV, characterized by recurrent febrile attacks. The natural history of the disease, which began in children and had a high mortality rate in the last century, is unknown in people over 65.

        This retrospective study included the records of 59 patients with FMF followed at Hôpital Tenon (Paris, France), representing 9% of the total number of patients followed for FMF. The median age was 73 years. Although all patients were treated with colchicine, the study population, born in the 1940s-1950s, had a late diagnosis (median age 28 years) and a delayed initiation of colchicine (35 years, median year of introduction 1980). 73% of patients had an elevated intercritical CRP on colchicine, and 37% had to receive an inteleukin-1 inhibitor, with good tolerability. The prevalence of AA amyloidosis was 10%. The most frequent comorbidities were cardiovascular (59% of patients) and, unexpectedly, hepatic (37%), with a high frequency of non-alcoholic, non-viral cirrhosis (27%) and no associated diabetes, suggesting a link with FMF. Nine patients (15%) had died at the time of collection, two from complications of FMF, two from hepatic cirrhosis, and five from infections.

             In conclusion, the study indicates that FMF can remain active after the age of 65, motivating specialized lifelong follow-up with CRP monitoring between attacks, as well as the prescription of biotherapy in the event of unsatisfactory disease control.

Caractéristiques de la fièvre méditerranéenne familiale après 65 ans.pdf

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