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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Clostridioides difficile infection as a potential trigger for Familial Mediterranean Fever attacks and fecal transplantation as a rescue

Premier auteur: Sophie Georgin-Lavialle

Revue: European Journal of Internal Medicine

Le lien vers l'article: https://doi.org/10.1016/j.ejim.2024.05.023

Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease in the world. It is associated with mutations in the MEFV gene, which encodes pyrin.

The diagnosis of Clostridium difficile infection is complex in patients with FMF, as during FMF crises, the most frequent symptoms include febrile abdominal pain accompanied by a biological inflammatory syndrome, manifestations common to both conditions.

The B toxin of Clostridium difficile is a specific activator of the pyrin inflammasome.

Clostridium difficile infection complicating FMF is a rare but serious and potentially fatal infection.

It should be suspected in FMF patients presenting with unexplained persistent inflammation and/or chronic abdominal pain and/or unusual diarrhea.

=> The B toxin of C. difficile can then be tested in stool samples to exclude a false resistance to colchicine and avoid mistakenly starting anti-interleukin 1 biotherapy.

=> C. difficile infection in an FMF patient must be actively treated, including fecal transplantation if necessary.

Clostridioides difficile infection as a potential trigger for Familial Mediterranean Fever.

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Could tocilizumab be used in familial Mediterranean fever? A systematic review

First author : P. Mertz

Review: Rheumatology

Link to article: https://doi.org/10.1093/rheumatology/keae338

Could tocilizumab be used in Familial Mediterranean Fever ?

Abstract:

Introduction:

Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease characterized by recurrent fever and serosal inflammation. Although colchicine is the primary treatment, around 10% of FMF patients do not respond to it, necessitating alternative therapies. Biologic treatments, such as IL-1β, TNF-α and IL-6 inhibitors, have been considered. However, the accessibility and cost of IL-1β inhibitors may limit their use in certain regions. Tocilizumab (TCZ), an IL-6 receptor inhibitor, offers an alternative, but its efficacy in FMF is not well-documented.

Results:

After selection, 14 articles were included: two double-blind RCTs, two retrospective studies and 10 case reports. Multicentre double-blind RCTs reported mixed results in FMF patients without AA amyloidosis due to genetic/classification heterogeneity of the available studies, possible misdiagnosed FMF patients and study design. Retrospective studies suggest that TCZ may benefit FMF patients with established renal AA amyloidosis, potentially preventing progression and managing flares more effectively. TCZ showed a safe profile with no specific adverse events, but data on its use during pregnancy or breastfeeding are lacking. There was no available data on the use of TCZ in paediatric FMF.

Conclusion:

This review summarizes the current state of research, safety and efficacy of TCZ in FMF. While IL1β inhibitors remain the first choice for colchicine-resistant or intolerant FMF patients, TCZ might be of interest in some selected FMF patients with established AA amyloidosis and resistance to colchicine and interleukin 1 inhibitors.

Could tocilizumab be used in familial Mediterranean fever?.pdf

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