EULAR/PReS endorsed recommendations for the management of familial Mediterranean fever (FMF): 2024 update

First author : Ozen S

Review: Annals of the Rheumatic Diseases

Reference: Ann Rheum Dis. 2025 Apr 9:S0003-4967(25)00084-6

Link to pubmed: EULAR/PReS endorsed recommendations for the management of familial Mediterranean fever (FMF): 2024 update - PubMed

2024 European Recommendations on Familial Mediterranean Fever (FMF) – Summary:

Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease worldwide. Due to its clinical and genetic variability, specialized management is essential. In 2024, the EULAR and PReS societies updated their guidelines.

General Principles:

• FMF requires specialist expertise for both diagnosis and management.

• The primary goal is complete control of inflammation, including subclinical inflammation, to prevent complications such as AA amyloidosis.

• Lifelong treatment is necessary, with strict adherence, primarily based on daily colchicine therapy.

• Care should be patient-centered, aiming to preserve quality of life.

Key Recommendations:

• Colchicine should be initiated as soon as a clinical diagnosis is made.

• The dosage must be tailored to tolerance and adherence (single or divided daily doses).

• If symptoms persist or subclinical inflammation remains, the dose should be increased within recommended limits (maximum 2 mg/day in children, 3 mg/day in adults).

• If colchicine fails despite good adherence, interleukin-1 blockers (anakinra, canakinumab) are recommended.

• Chronic musculoskeletal manifestations may require additional treatments (DMARDs, biologics).

• Regular monitoring (clinical, biological, toxicity, adherence) is essential.

• Colchicine should be continued during pregnancy and breastfeeding.

• During acute attacks, colchicine should be maintained at the same dose, with symptomatic treatment added (e.g., NSAIDs).

• A minimum core set of assessment criteria is proposed: attack frequency, quality of life, biological markers (CRP, SAA).

Quality indicators, clinical priorities (especially adherence), and implementation strategies are provided to harmonize care across centers.

Recommandations approuvées par l’EULAR et la PReS FMF.pdf

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Genetic and clinical features of Familial Mediterranean Fever in a cohort of patients with kidney failure

First author: Ahmed Sheyyab

Journal: Journal of Nephrology

Link to the article: doi.org/10.1007/s40620-025-02272-y

Author of the abstract: Rim BOURGUIBA

Introduction

Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease worldwide. In its classic form, it is mainly associated with mutations in exon 10 of the MEFV gene. AA amyloidosis is the most severe complication of FMF.

The aim of this study was to compare the frequency of MEFV variants in hemodialysis patients versus healthy controls in a Mediterranean country, Jordan.

Methods

This was a cross‑sectional study including 78 patients with end‑stage kidney disease on hemodialysis and 201 healthy controls in Jordan. All patients underwent Sanger sequencing for the main MEFV variants. The following variants were tested: p.E148Q, p.P369S, p.F479L, p.M680I (G/C), p.M680I (G/A), p.I692del, p.M694V, p.M694I, p.K695R, p.V726A, p.A744S, and p.R761H.

Patients carrying a variant were then clinically assessed according to the Tel‑Hashomer criteria. Five underwent rectal biopsy to detect amyloidosis.

Results

Among dialysis patients, 16% had at least one MEFV variant versus 12.9% in the control group (not significant). The two most frequent mutations in the hemodialysis group were M694V (p = 0.035) and V726A (p = 0.009). The variants detected in both groups are summarized in Table 1. In the control group without renal failure, 22 individuals were heterozygous for the E148Q variant. Three patients met diagnostic criteria for FMF, and one case of AA amyloidosis was confirmed by biopsy.

Conclusion

FMF is the most common autoinflammatory disease in Mediterranean countries, yet it remains underdiagnosed even in high‑risk populations. This diagnostic delay leads to complications, notably AA amyloidosis. This study shows that 4% of hemodialysis patients were diagnosed with FMF. It also confirms the non‑pathogenic nature of the E148Q variant, which was detected in 22 healthy, asymptomatic individuals.

Overall, these findings underscore the importance of testing for MEFV mutations in patients with AA amyloidosis in countries where FMF is highly prevalent, in order to offer appropriate treatment to prevent AA amyloidosis and progression to renal failure.

Genetic and clinical features of familial Mediterranean fever in a cohort of patients with.

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Adult Familial Mediterranean Fever (FMF): is a single MEFV mutation sufficient to cause severe disease?

Article title: Clinical characteristics and outcomes of adult FMF patients: comparison between those with one versus two

pathogenic MEFV exon 10 mutations

First author: Anaël Dumont

Journal: Joint Bone Spine

Link to the article: doi.org/10.1016/j.jbspin.2025.105850

Author of the abstract: Rim BOURGUIBA

Introduction

Familial Mediterranean Fever (FMF) is an autoinflammatory disease caused by mutations in MEFV. While two pathogenic mutations typically lead to a classic and more severe phenotype, the clinical expression in patients with only one pathogenic mutation remains debated. This study compared adult FMF patients according to whether they carried one or two pathogenic MEFV mutations.

Methods

A French single‑center retrospective cohort included 581 adult FMF patients: 178 with a single pathogenic mutation and 403 with two pathogenic mutations. Diagnosis used Eurofever/PRINTO criteria, and all patients underwent MEFV sequencing. A focused analysis compared M694V/E148Q versus M694V/WT.

Results

Compared with biallelic patients, heterozygous patients were older at diagnosis and disease onset, had more personal and family history of recurrent aphthous stomatitis, and a higher BMI. No AA amyloidosis was observed in heterozygotes, and they required lower colchicine doses. These differences remained significant after adjustment for age at onset. No clinical difference was found between M694V/E148Q and M694V/WT.

Conclusion

Adult FMF patients with a single pathogenic MEFV mutation show distinct clinical features and outcomes compared with those carrying two mutations. Findings highlight FMF phenotypic heterogeneity and support tailoring management to the patient’s genetic profile.

FMF adulte : une seule mutation MEFV suffit‑elle à rendre la maladie sévère.

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