Iron Deficiency in Familial Mediterranean Fever: A Studyon 211 Adult Patients From the JIR Cohort

First author: Ilenia Di Cola et al

Review: American Journal of Hematology

Link to article: https://doi.org/10.1002/ajh.27549

Familial Mediterranean Fever (FMF) is the most common monogenic autoinflammatory disease worldwide, associated with mutations in the MEFV gene. Patients experience recurrent and self-limited episodes of fever, abdominal pain, and chest pain. There is no specific association between anemia and FMF, except that patients with chronic inflammation may have inflammatory microcytic anemia.

However, chronic anemia can lead to fatigue, and fatigue is known to be a trigger for FMF. Therefore, patients with fatigue due to anemia may experience more frequent flare-ups of the disease and a reduced quality of life. Iron deficiency can cause fatigue even in the absence of anemia. Fatigue is also commonly reported in FMF. Therefore, it may be beneficial to check for iron deficiency without anemia as one of the causes of fatigue in FMF, especially since fatigue can be considered a trigger for their flare-ups.

Our study explores the prevalence of iron deficiency in 211 adult patients with Familial Mediterranean Fever (FMF). The main goal was to determine the association between iron deficiency (defined by ferritin < 27 ng/mL) and various clinical, biological, and therapeutic parameters.

In total, 31.8% of FMF patients had ferritin < 27 ng/mL, mostly young women. Iron deficiency, even without anemia, potentially contributes to fatigue, a frequent trigger of inflammatory flare-ups. Possible causes include excessive menstrual losses not compensated by a diet rich in iron, low consumption of animal proteins, or digestive bleeding exacerbated by the use of NSAIDs.

Patients with low ferritin had lower hemoglobin (Hb) levels and BMI, and required higher doses of colchicine (2 mg/day on average). The impact of colchicine on intestinal iron absorption remains to be studied.

This work highlights the importance of monitoring ferritin levels in Familial Mediterranean Fever (FMF) due to the simplicity and global accessibility of this test, including in emerging countries. In the case of significant iron deficiency, supplementation is recommended to alleviate symptoms such as fatigue and anemia, which can trigger FMF flare-ups and maintain a vicious cycle of fatigue in patients.

Iron deficiency in FMF.pdf

Download PDF • 288KB

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.

Download • 331KB

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

Download PDF • 1.08MB