Familial Mediterranean fever, from pathogenesis to treatment: a contemporary review
Abdurrahman Tufan1, Helen J Lachmann2
1Department of Internal Medicine, Division of Rheumatology, Gazi University, Ankara, Turkey
Abstract:
Familial Mediterranean fever (FMF) (OMIM #249100) is the most common hereditary autoinflammatory disease in the world. FMF is caused by gain of function mutations of MEFV gene which encodes an immune regulatory protein, pyrin. Over the last few years, we have witnessed several new developments in the pathogenesis, genetic testing, diagnosis, comorbidities, disease related damage and treatment approaches to FMF. Elucidation of some of the pathogenic mechanisms has led to the discovery of pathways involved in inflammatory, metabolic, cardiovascular and degenerative diseases. The use of next generation sequencing in FMF has revealed many new gene variants whose clinical significance may be clarified by developing functional assays and biomarkers. Clinically, although FMF is considered an episodic disease characterized by brief attacks, recent systematic studies have defined several associated chronic inflammatory conditions. Colchicine is the mainstay of FMF treatment, and interleukin (IL)-1 antagonists are the treatment of choice in refractory or intolerant cases. Experience of IL-1 antagonists, anakinra and canakinumab, is now available in thousands of colchicine resistant or intolerant FMF patients. In this contemporary review, we surveyed current FMF knowledge in the light of these recent advances.
Insights
Familial Mediterranean fever (FMF) is a common autoinflammatory disease caused by MEFV gene mutations. Recent advances have improved understanding of its pathogenesis, genetics, and treatment, including IL-1 antagonists for resistant cases.
Area of Science:
- Genetics and immunology
- Autoinflammatory diseases
- Molecular medicine
Background:
- Familial Mediterranean fever (FMF) is the most prevalent hereditary autoinflammatory disorder globally.
- FMF arises from gain-of-function mutations in the MEFV gene, encoding the pyrin immune protein.
- Recent years have seen significant progress in understanding FMF's pathogenesis, genetics, diagnosis, comorbidities, and treatment.
Purpose of the Study:
- To provide a contemporary review of Familial Mediterranean fever (FMF).
- To highlight recent advancements in FMF pathogenesis, genetic testing, diagnosis, comorbidities, and therapeutic strategies.
- To discuss the evolving landscape of FMF management, including novel treatment options.
Main Methods:
- Comprehensive literature review of recent developments in FMF research.
- Analysis of new findings in genetic testing, including next-generation sequencing.
- Evaluation of current treatment modalities, including colchicine and IL-1 antagonists.
Main Results:
- Elucidation of pathogenic mechanisms has revealed links to inflammatory, metabolic, cardiovascular, and degenerative diseases.
- Next-generation sequencing has identified new MEFV gene variants requiring further functional validation.
- Systematic studies have defined chronic inflammatory conditions associated with FMF, beyond episodic attacks.
- Interleukin (IL)-1 antagonists (anakinra, canakinumab) show efficacy in colchicine-resistant or intolerant FMF patients.
Conclusions:
- Significant progress has been made in understanding FMF, driven by genetic and molecular research.
- Next-generation sequencing and functional assays are crucial for clarifying the clinical significance of new gene variants.
- FMF management has evolved, with IL-1 antagonists offering effective alternatives for refractory cases.
- A comprehensive understanding of FMF encompasses its episodic nature, chronic inflammatory comorbidities, and advanced treatment options.
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