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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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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Anti-proinflammatory cytokine biotherapy can prevent the progression of AA amyloidosis to end-stage renal disease.

First author: Kvacskay P

Revue : Annals of Rheumatic disease

Reference:  PMID: 38653531 ; DOI: 10.1136/ard-2023-225114

Lien vers pubmed: https://pubmed.ncbi.nlm.nih.gov/38653531/

Introduction:

AA amyloidosis (AA) can be the consequence of any chronic inflammatory disease. AA is associated with chronic inflammatory diseases (cid+AA), autoinflammatory syndromes (auto+AA) or AA of unknown origin or idiopathic AA (idio+AA). The major organ manifestation is renal AA that can progress to end-stage renal disease (ESRD) and multiple organ failure.

Materials and methods:

This study is a monocentric retrospective analysis of the renal outcome and survival of patients with cid+AA (n=34), auto+AA (n=24) and idio+AA (n=25) who were treated with cytokine-inhibiting biological disease-modifying antirheumatic drugs (bDMARDs).

Results

83 patients with renal AA amyloidosis were identified and followed for a mean observation period of 4.82 years.

The patients were 34 with cid+AA (40.5%), including 18 with rheumatoid arthritis and 8 with chronic inflammatory bowel disease; 25 with idio+AA (30.5%) and 24 with auto+AA (29%), including 22 with familial Mediterranean fever and 2 with cryopyrinopathies.

Levels of C-reactive protein (CRP), serum amyloid A protein (SAA) and proteinuria were significantly reduced under treatment with biotherapy.

With biotherapy, progression to ESRD was prevented in 88% of patients in the auto+AA group, 81% in the idio+AA group and 60% in the cid+AA group during the study period.

Thirty-four patients received tocilizumab in the cid+AA (n=18) and idio+AA (n=16) arms. Tocilizumab was more effective in reducing CRP and progression to ESRD and death than other biotherapies. No patient taking tocilizumab during the study period died.

Patients with autoinflammatory diseases were excluded from this analysis with tocilizumab as this biotherapy is not indicated for inflammatory diseases.

Conclusion

Anti-proinflammatory cytokine biotherapies reduce systemic inflammation in various diseases associated with the development of AA amyloidosis, leading to a reduction in proteinuria and prevention of ESRD.

In this retrospective series, tocilizumab tested in 34 patients with AA amyloidosis complicating chronic or idiopathic inflammatory disease was more effective than other biotherapies in controlling systemic inflammation, leading to improved renal and overall survival in these patients.

Figures

Figure 1. Serum biomarkers and proteinuria are analysed in subgroups of AA patients with chronic inflammatory disease cid+AA (cid+AA), autoinflammatory disease auto+AA (auto+AA) and idiopathic disease (idio+AA).

Biotherapy was initiated at the first visit (baseline) and compared with the last documented visit 4 to 6 years later. CRP (A), SAA (B), serum creatinine (C), sample proteinuria (D), serum albumin (E), total serum protein (F), serum IgG (G) and NT-BNP (H) were analysed at the first and last visits.

Figure 2: Patients treated with Tocilizumab (TOC) were compared with other biotherapies.

(A): Patients with cid+AA (cid+AA) and idio+AA were followed every 6 months until the last visit.

(B) and (C): Analyses of cid+AA (cid+AA) and idio+AA subgroups are shown. (D) Across the cohort tocilizumab (TOC) prevented progression of AA to other organs and death (D).

bDMARD can prevent the progression of AA.pdf

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