Familial Mediterranean Fever (FMF) and the Mediterranean diet: what impact on the severity of the disease?

Title in English: Association of Mediterranean diet adherence with Familial Mediterranean Fever severity in a Lebanese cohort.

First author: R. Hammoud.

Journal: Pediatric Rheumatology

Reference: Pediatr Rheumatol Online J. 2025 Nov 21;23(1):122.

Link to PubMed: https://pubmed.ncbi.nlm.nih.gov/41272709/

Summary author: Dr Catherine Grandpeix-Guyodo

Introduction:

Familial Mediterranean Fever (FMF) is the most common autoinflammatory disease worldwide. It is associated with pathogenic variants, classically in exon 10 of the MEFV gene. The variable expressivity of this disease is linked to the type of MEFV variant (particularly M694V), but epigenetic and environmental factors probably also play a role. Previous studies have suggested that a diet rich in fat and salt may worsen FMF symptoms, whereas a diet rich in antioxidants and vitamins may improve inflammation and quality of life. The Mediterranean diet, which is recommended for the prevention of other diseases, could therefore be of interest in FMF.

This study aimed to explore the relationship between adherence to the Mediterranean diet (MD) and the severity of familial Mediterranean fever (FMF) in a Lebanese cohort. It also took into account the influence of genetic background, lifestyle, and comorbidities on FMF severity.

Patients and methods:

This was a cross‑sectional questionnaire‑based study of 101 patients with confirmed FMF in Lebanon, conducted between January 2023 and January 2024. Patients were required to be between 18 and 65 years old and to have FMF. Data were collected using a structured questionnaire on demographic information, socioeconomic status, disease manifestations, comorbidities, treatments, and lifestyle habits. The questionnaire was pre‑tested and offered in Arabic or English.

FMF severity, adherence to the Mediterranean diet, and physical activity were assessed using scores.

Results:

A total of 101 patients, 58% of whom were women, were included, with a mean age of 35.7 years, and 55% were smokers. No significant sociodemographic differences were observed according to the different levels of adherence to the Mediterranean diet.

Genotype data were available for only 51/101 patients, of whom 17.6% were M694V homozygotes, and 64.6% were other homozygotes or compound heterozygotes.

Analysis of patients diets showed low adherence to the Mediterranean diet in 34%, moderate adherence in 48%, and good adherence in 19%. Overall, consumption of fish, fruit, and vegetables was below recommendations, whereas intake of cereals, pastries, and red meat was too high.

The only significant difference observed according to Mediterranean‑diet adherence was diarrhea, which was reported almost twice as often in patients with low adherence. Other symptoms, attack frequency, and FMF severity did not differ significantly.

Obesity and the presence of comorbidities (rheumatologic, IBD, cardiovascular) were significantly associated with more severe FMF.

Patients with severe FMF had a longer smoking history and smoked more cigarettes per day. High physical activity levels were more frequent in severe forms (73%), whereas moderate activity predominated in mild (82%) and intermediate (88%) forms.

Discussion:

A potentially beneficial effect of the Mediterranean diet on the digestive tract was observed, with less diarrhea among patients adhering to this diet. This is consistent with the expected effects on the digestive mucosa, microbiota, and the reduction of pro‑inflammatory interleukin secretion.

However, no significant association was found between FMF severity and adherence to the Mediterranean diet.

The association between more severe forms of FMF and intense physical activity should be taken into account: it is advisable to recommend adapted physical activity in order to avoid mechanical stress that could trigger attacks.

The limitations of this study include the cohort size and its specific characteristics, with generally lower adherence to the Mediterranean diet than would be expected.

In conclusion:

This study, the first conducted in Lebanon on this topic, does not demonstrate a direct association between adherence to the Mediterranean diet and FMF severity, but it does suggest a potential protective effect of the Mediterranean diet against FMF‑related diarrhea. It highlights the high prevalence of poor adherence to this diet and the failure to meet nutritional recommendations for most of its components. The multifactorial nature of FMF supports a comprehensive management approach that integrates targeted dietary and lifestyle strategies alongside treatments, with personalized nutrition and behavioral interventions aimed at improving prognosis and patients quality of life.

Colchicine-resistant Familial Mediterranean Fever: triggering factors are highly prevalent and reduced under IL-1 inhibition

Article title: Do we consider enough the presence of triggering factors in the evaluation of patients with FMF? Triggering factors are highly prevalent in colchicine-resistant FMF patients.

First author: Bayram Farisogullari

Journal: Internal and Emergency Medicine

Link to the article: https://pubmed.ncbi.nlm.nih.gov/38103114/

Introduction

The objective of this study was to investigate the frequency of triggering factors in patients with Familial Mediterranean Fever (FMF) who are resistant to colchicine and in those who are responsive to colchicine, and to assess the impact of interleukin-1 (IL-1) antagonist therapy on triggering factors in colchicine-resistant patients.

Patients and Methods

Colchicine-resistant FMF patients treated with IL-1 antagonists and colchicine-responsive patients treated with colchicine and experiencing ≤ 3 attacks in the previous year were questioned about the presence of 12 different triggering factors: cold exposure, emotional stress, fatigue, intense physical activity, menstruation (for women), sleep deprivation, prolonged standing, long-distance travel, high-fat diet, prolonged fasting, infections, and trauma.

Colchicine-resistant patients were questioned for two periods: before and after initiation of IL-1 antagonist therapy.

Results

A total of 63 patients were included, comprising 28 colchicine-resistant patients (19 treated with anakinra and 9 with canakinumab) and 35 colchicine-responsive patients. Only half carried two pathogenic mutations in exon 10 of the MEFV gene (Table 1). Overall, 77.8% of patients reported at least one triggering factor, with a mean number of 2.6 per patient.

The most common triggering factors, in decreasing order of frequency, were emotional stress, menstruation, cold exposure, prolonged standing, and long-distance travel. Triggering factors accounted for approximately one-third of attacks, and 57.1% of patients reported using avoidance strategies. The frequency of triggering factors was higher in colchicine-resistant patients than in colchicine-responsive patients (89.3% vs 68.6%; p = 0.04).

Among colchicine-resistant patients, the frequency of triggering factors decreased from 89.3% to 32.1% under IL-1 antagonist therapy, and the proportion of attacks initiated by a triggering factor decreased from 27.8% to 14.4% (p < 0.001) (Table 2).

Discussion

Triggering factors were more frequent in colchicine-resistant patients than in colchicine-responsive patients. Treatment with IL-1 antagonists appeared to reduce both the number of triggering factors and the proportion of attacks induced by these factors.

Conclusion

Triggering factors are common in FMF and should be systematically assessed, particularly when colchicine resistance develops. IL-1 antagonists reduce their impact and may be useful as long-term therapy or as preventive treatment during predictable exposures.

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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