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The needed daily dose of colchicine in patients with Familial Mediterranean Fever may be higher in women: a study on behalf of the JIR cohort.

Author: Di Cola et al.

Ref : Di Cola et al, Arthritis Res Ther. 2025 Mar 19;27(1):59.


La dose quotidienne nécessaire de colchicine chez les patients atteints de Fièvre Méditerranéenne Familiale pourrait être plus élevée chez les femmes

Summary


To date, no data exist on the relationship between daily colchicine dosage and body weight in patients with Familial Mediterranean Fever (FMF). This question is frequently raised by patients or their parents during consultations. The objective of our study was to describe the daily colchicine dosage in a cohort of patients with FMF.


We conducted a retrospective analysis from 2016 to 2023 on adult FMF patients who were prospectively followed at the French National Reference Center for Auto-inflammatory Diseases at Tenon Hospital.


Among the 272 patients studied, 149 were women (57.8%), with a mean age of 43 years. The average weight was 67.8 kg, and the mean BMI was 24.2 kg/m². Colchicine was taken by 96% of the patients. A subgroup of 30 patients was receiving 2.5 mg/day of colchicine: the majority were women (n=23; 76.7%; p=0.018), with a significantly lower average weight (p=0.019); in fact, 26 out of 30 (87%) weighed less than 50 kg. Female sex was associated with a higher daily dose of colchicine (p=0.0208), whereas no significant correlation was found with weight (p=0.4073).


No signs of toxicity were observed in patients receiving 2.5 mg/day of colchicine, including those weighing under 50 kg, the majority of whom were women.


One hypothesis is that this increased need for colchicine in some women may be related to hormonal factors, with a possible hyperactivation of pyrin.


This is the first study to examine the relationship between weight and colchicine dosage in adults with FMF, highlighting a potential link with female sex.


This work provides reassurance to patients receiving 2.5 mg/day of colchicine: there is no toxicity at this dose in the absence of renal impairment.




Liver disease complicating Familial Mediterranean Fever: a study on 66 patients out of 533 adult from the JIR cohort

Updated: Mar 18

First author: M. DELPLANQUE et al,

Journal: Liver International

Liver disease complicating Familial Mediterranean Fever:

Abstract:

Background: Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease, associated with MEFV mutations. FMF patients can experience liver involvement, potentially leading to cirrhosis.

Objectives: This study aimed to evaluate liver involvement in FMF patients at a French tertiary center for adult FMF.


Methods: We conducted an observational study with FMF patients displaying 2 pathogenic MEFV mutations at the Adult National Reference Centre for Autoinflammatory Diseases and Inflammatory Amyloidosis (CEREMAIA) in Paris and included in the JIR cohort. MEFV heterozygous patients and those with other liver disease causes were excluded.


Results: Among 533 FMF patients 12.4% had chronic liver abnormalities, with 30% who developed cirrhosis 54 years [36-57] in median after disease onset. Forty-seven percent were colchicine resistant, and 41% received interleukin-1 inhibitors. Cirrhotic patients experienced delayed hepatopathy diagnosis, prolonged FMF diagnosis delay, and late-onset treatment initiation compared to those with only liver function test abnormalities. Colchicine resistance and interleukin-1 inhibitor use were more common in cirrhotic patients. Body mass index and AA amyloidosis rates did not differ significantly between groups. Twenty-one patients undergone liver biopsies including 14 cirrhotic patients revealing steatohepatitis in 12 cases and probable steatohepatitis in 4. Other lesions, like iron overload and sinusoidal dilatation, were sporadically observed.


Conclusion: FMF patients are at risk of chronic liver disease. Regular liver function monitoring is crucial, particularly in case of persistent inflammation, due to the risk of progression to cirrhosis and its associated morbidity and mortality.


Lay Summary

More than, 10% of FMF patients develop chronic liver abnomalities over time and 4% cirrhosis. High-risk includes those with 2 MEFV mutations and colchicine resistance and chronic liver disease often begins after age 55 in FMF patients. In FMF patient with impaired liver function optimizing treatment targeting chronic inflammation is a key point in their care.

 

Liver biopsy of FMF patient

a. Liver biopsy with cirrhosis (sirius red staining)

b. Same liver biopsy with steatohepatitis associating steatosis, hepatocellular ballooning and inflammation (H&E staining)


Biopsie du foie d'un patient atteint de FMF
Biopsie du foie d'un patient atteint de FMF

Complications of cirrhosis in FMF patients

(A) Esophageal varices visualized by upper gastrointestinal endoscopy

(B) Hepatomegaly and ascite of a cirrhotic FMF patient detected in an abdominal CT scan

(C) Hepatomegaly and ascite of a cirrhotic FMF patient detected in an abdominal CT scan


Complications de la cirrhose chez les patients atteints de FMF
Complications de la cirrhose chez les patients atteints de FMF

Table 1. Demographic and clinical characteristics of the enrolled cohort.

Table 1. Demographic and clinical characteristics of the enrolled cohort.

Data are presented as median [Q1-Q3]. N= number of patients

††CRP C protein reactive, BMI Body Mass Index, FMF Familial Mediterranean fever, W women, M men



Table 4. Complication and Child Pugh Score of FMF patients with cirrhosis (n=20)

Table 4. Complication and Child Pugh Score of FMF patients with cirrhosis (n=20)

Transjugular intrahepatic portosystemic shunts (TIPS)

(% among cirrhotic patients)



Diagnosis traps for patients with acquired NLRP3 mutation (CAPS)

First author: M. DELPLANQUE et al,

Journal: European Journal of Internal Medicine

Pièges diagnostiques chez les patients atteints d'une mutation acquise de NLRP3 (CAPS)

Summary:

The article highlights the diagnostic challenges of cryopyrin-associated periodic syndromes CAPS, caused by NLRP3 gene mutations. These autoinflammatory diseases include three main forms: familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and Chronic Infantile Neurological Cutaneous and Articular (CINCA) syndrome.

The study presents two cases of patients with acquired somatic NLRP3 mutations, illustrating the difficulty of diagnosis due to atypical phenotypes:

  • Patient 1 (P1): A 46-year-old woman with neuroinflammatory symptoms (persistent headaches, aseptic meningitis, hearing loss), initially misdiagnosed. A somatic M406I mutation was identified after 10 years of diagnostic wandering, explaining her atypical presentation. Treatment with anti-IL-1 drastically improved her condition.

  • Patient 2 (P2): A male patient with severe CINCA syndrome since infancy, presenting with urticaria, arthritis, and growth delay. His genetic diagnosis was challenging, and the M406V mutation was only detected at the age of 15 using deep sequencing techniques.

The authors emphasize that somatic mutations in the NACHT domain of NLRP3 lead to constitutive activation of the inflammasome, resulting in excessive IL-1β production and severe chronic inflammation. The study underscores the importance of advanced genetic sequencing to detect these mutations, particularly in atypical cases.

Conclusion

Identifying somatic mutations in NLRP3 is crucial to avoid misdiagnosis and ensure effective treatment. Diagnostic delays can be prolonged in the absence of classic clinical signs (such as urticaria), and next-generation sequencing is essential for detecting low-percentage mosaicism.



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