Premenstrual syndrome and inflammatory activity in adolescent Familial Mediterranean Fever

• English title: Premenstrual syndrome and inflammatory activity in adolescent familial Mediterranean fever

• First author: Nigar Aliyeva

• Journal: Rheumatology

• Reference: Rheumatology (Oxford). 2026:keag169. doi: 10.1093/rheumatology/keag169. Online ahead of print.

• PubMed link: https://pubmed.ncbi.nlm.nih.gov/41936095/

• Abstracted by: Dr. Catherine Grandpeix-Guyodo

Key points - Premenstrual syndrome and inflammatory activity in adolescent familial Mediterranean fever

1. Premenstrual syndrome (PMS) is less frequent in FMF patients treated with colchicine than in healthy controls.

2. In FMF patients, PMS is associated with higher disease activity, systemic inflammation, and poorer treatment adherence. PMS severity appears to be proportional to the level of inflammation.

3. Colchicine may prevent PMS by reducing inflammation, which could explain the lower prevalence of PMS in colchicine-treated FMF patients compared with controls.

Introduction

PMS is linked to hormonal fluctuations, but immunological and inflammatory mechanisms also seem to contribute to symptom expression. Cytokine fluctuations during the menstrual cycle and the direct activation of the pyrin inflammasome by steroid catabolites support a direct link between reproductive physiology and inflammatory pathways.

However, there are limited clinical data on PMS in adolescents with FMF, and on its association with disease activity or adherence to colchicine treatment.

Patients and methods

This was a prospective, single-center Turkish study comparing adolescents aged 12 to 18 years with and without FMF, focusing on PMS. Menarche had to have occurred at least 6 months earlier; cycles had to be regular and bleeding last fewer than 7 days. FMF patients were required to have two pathogenic MEFV variants. Disease activity score (AIDAI), number of attacks per month (1 versus several), and biological inflammatory markers were collected, along with an assessment of PMS severity (PMSS).

Results

Mean age in both groups was 16 years. Mean height was significantly lower in the FMF group, while weight did not differ. Half of the FMF patients had not experienced a flare in the previous 6 months. Among 40 adolescents with FMF treated with colchicine, only 45% had PMS, compared with 75% among 40 controls. The difference in dysmenorrhea prevalence was not statistically significant, but longer menstruation and heavier bleeding were reported in FMF patients (p<0.05). PMS was more frequent and more severe in controls than in FMF patients.

Among FMF patients, those with PMS had higher AIDAI scores and more frequent FMF attacks. Blood inflammatory markers were also higher in this group. A clear correlation was observed between attack frequency and PMS severity.

There was also an association between PMS frequency and poor adherence to colchicine treatment.

Discussion

PMS appears less frequent in FMF, but PMS symptoms increase with inflammation. This suggests that colchicine, by modulating inflammation, could reduce hormonal symptoms and thus decrease PMS frequency. PMS is also more common in FMF patients with poor adherence to colchicine.

During the menstrual phase, decreased estrogen and increased IL-6 have been shown to intensify inflammation, which aligns with the observation that menstruation can trigger FMF attacks. Colchicine could therefore attenuate inflammatory fluctuations and modulate PMS.

Regarding the higher frequency of heavy bleeding during menstruation in FMF patients, one hypothesis is repeated use of anti-inflammatory drugs.

This study has limitations, including the small cohort size and its single-center design.

Conclusion

PMS is less frequent in FMF patients treated with colchicine than in healthy controls. In FMF patients, PMS is associated with higher disease activity, systemic inflammation, and poorer treatment adherence. Colchicine may prevent PMS by reducing inflammation, which could explain the lower frequency of PMS compared with the control population.

Anakinra treatment in colchicine-resistant or colchicine-intolerant Familial Mediterranean Fever: real-world experience

Summary by Dr Catherine Grandpeix-Guyodo

First author: Tuğba Ocak

Journal: Medicina

Reference: Medicina (Kaunas). 2025 Apr 25; 61: 792

Link to PubMed: https://pubmed.ncbi.nlm.nih.gov/40428750/

Introduction:

Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease worldwide. It is associated with MEFV gene mutations and is characterized by recurrent inflammatory attacks, particularly with abdominal pain. The most severe complication is AA amyloidosis. The recommended treatment is colchicine to prevent attacks and complications. In some patients, colchicine at the maximum tolerated dose is insufficient to prevent attacks, while others do not tolerate colchicine. Anti–interleukin‑1 agents are effective in cases of colchicine resistance or intolerance. This Turkish team investigated treatment with anakinra in colchicine‑resistant/intolerant FMF patients, focusing on their clinical characteristics, treatment duration, treatment response, possible extension of injection intervals, and long‑term outcomes.

Patients and methods:

This single‑center retrospective study included 68 FMF patients with colchicine resistance or intolerance who required initiation of anakinra at a dose of 100 mg/day. Colchicine resistance was defined as at least one attack per month despite the maximum tolerated daily dose of colchicine. Colchicine intolerance was defined as the inability to increase the colchicine dose because of digestive side effects.

Results:

Among these 68 patients, the median age was 40.2 years and 57.3% were women. Of the 60 patients who had undergone genetic testing, 32 patients (53%) had two pathogenic MEFV mutations, 26 (43%) were heterozygous for pathogenic mutations, and 2 had no identified mutation.

Fifteen patients had AA amyloidosis. All patients were treated with colchicine before starting anakinra, at a median dose of 2 mg/day, and 63 patients continued colchicine in parallel. Median follow‑up was 34 months.

Treatment was effective in the majority of patients, with significant reductions in the Pras score, ESR, CRP, SAA, and proteinuria when present.

In 21 patients, remission was achieved under treatment, allowing an increase in the interval between anakinra injections to every 2 days, then every 3 days. Eight of these patients were able to discontinue anakinra completely while continuing colchicine alone. Only 2 patients relapsed within the month following complete treatment withdrawal.

The main adverse events were injection‑site reactions.

Seventeen additional treatment discontinuations were reported, mostly due to insufficient response (7 patients) or adverse events (7 patients).

Four patients received anakinra during pregnancy without adverse effects in either the mother or the baby.

Six kidney‑transplant recipients were treated with anakinra, one of whom died from COVID‑19 pneumonia.

Discussion:

This study shows that treatment with anakinra in patients who are resistant or intolerant to colchicine leads to rapid and sustained improvement in clinical signs and inflammatory markers, with good tolerability. Injection intervals could be extended to every 2 or even 3 days while maintaining clinical and biological response. Proteinuria decreased in some patients, suggesting a potential benefit in those with AA amyloidosis. Treatment was also well tolerated, with no adverse effects reported in the 4 pregnant women.

In practice:

In this study of 68 Turkish adults with FMF, anakinra was rapidly effective and well tolerated in the long term in patients who were resistant or intolerant to colchicine.

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.