The project led by A.Ma.R.A.M APS will be presented on February 23, 2026, at the Bari Policlinic.
Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disease that primarily affects populations in the Mediterranean region. Despite its well-defined genetic basis, FMF does not manifest uniformly across countries. Genetic, environmental, and healthcare system differences significantly influence the disease course, timeliness of diagnosis, and response to treatment.
This is the context of a major international research project, closely monitored by A.Ma.R.A.M. APS – Alta Murgia Rare Diseases Association, which will be officially presented on February 23, 2026, during the training event:
“Building the future of rare disease – Networks, pathways, and clinical leadership”,
organized by the Intercompany Research and Care Center for Rare Diseases of the AOUC Policlinico di Bari – Giovanni XXIII, on the occasion of World Rare Disease Day.
The Research Project
The project is part of the healthcare, research, and teaching activities of the FMF and autoinflammatory diseases reference center at the “A. Murri” Medical Clinic (Director: Prof. Piero Portincasa, Professor of Internal Medicine), within the Department of Precision and Regenerative Medicine and Ionian Area (Director: Prof. Francesco Giorgino), University of Bari Aldo Moro (Rector: Prof. Roberto Bellotti) at the Azienda Ospedaliero-Universitaria Consorziale Policlinico (General Director: Dr. Antonio Sanguedolce, Medical Director: Dr. Donato Sivo).
Thanks to the international research team at the Medical Clinic, the study also involved the Medical Genetics Unit at the Policlinic and three Lebanese universities between Beirut and Tyre.
The research aims to better understand how FMF manifests in different contexts by comparing two Mediterranean populations: Italy (Apulia) and Lebanon. The findings contribute to strengthening clinical knowledge of the disease and improving diagnosis, treatment, and patient management.
What is FMF and why is it a complex disease?
FMF is caused by mutations in the MEFV gene, which encodes the protein pyrin, a key regulator of innate inflammation. Alterations in this mechanism lead to recurrent episodes of fever and inflammation of the serous membranes (peritoneum, pleura, and joints), with symptoms such as abdominal and chest pain, arthralgia, and myalgia.
If not properly treated, FMF can lead to a serious and potentially fatal complication: renal amyloidosis. Therefore, early diagnosis and ongoing therapy are essential.
The Study: A Comparison between Italy and Lebanon
The study analyzed 443 patients with FMF:
- 165 Italian patients
- 278 Lebanese patients
Clinical, genetic, and therapeutic data were collected, along with an in-depth questionnaire administered to a subgroup of patients to assess disease awareness, frequency and severity of attacks, diagnostic errors, and response to treatment.
Late Diagnosis and Disease Awareness
One of the most significant findings concerns diagnostic delay.
In Italy, diagnosis occurs on average 8–10 years after the onset of symptoms, while in Lebanon the delay is much shorter (about 3 years).
Lebanese patients show greater awareness of FMF before diagnosis, often due to a positive family history. In Italy, however, FMF remains underrecognized, with a high rate of misdiagnosis, especially appendicitis and gastrointestinal disorders, which in some cases leads to unnecessary surgery.
Genetics and disease severity
Significant genetic differences emerged:
- In Italian patients, variants such as R202Q, E148Q, and R761H are prevalent and are often associated with milder forms or variable expressivity.
- In Lebanese patients, “founder” mutations such as M694V, M694I, and V726A are more frequent and historically associated with more severe forms.
These genetic differences are reflected in clinical presentation: Lebanese patients experience more frequent attacks, more intense symptoms, and higher fevers, while Italian patients, on average, show a milder disease course.
Therapies and Access to Care
Colchicine remains the first-line treatment for FMF and is used in almost all patients. However, the therapeutic response is better in Italian patients, with a more marked reduction in fever and symptom severity.
A key factor is access to anti-IL-1 biological therapies (such as anakinra and canakinumab), which are more readily available in Italy than in Lebanon, where economic and healthcare system constraints limit their use.
Beyond Genetics: Environment and Healthcare System
One of the most innovative aspects of the study is the comparison between patients with identical genetic mutations. Even in these cases, Lebanese patients show earlier disease onset and more severe manifestations, confirming the crucial role of environmental, cultural, healthcare, and organizational factors.
Project presentation on February 23, 2026
The results of this important research project will be presented on February 23, 2026, during the training event:
“Building the Future of Rare Diseases – Networks, Pathways, and Clinical Leadership”
De Benedictis Hall – Bari Policlinic
8:30 AM – 5:00 PM
The event represents a key opportunity for discussion between clinicians, researchers, institutions, and patient associations, and is fully aligned with the mission of A.Ma.R.A.M. APS: promoting research, raising awareness, and improving the quality of life of people living with rare diseases.
Scientific Source
The article is based on the scientific study:
“Genetic and Clinical Features in Italian and Lebanese Subjects with Familial Mediterranean Fever (FMF)”,
written by Nour Jaber, Mohamad Khalil, Hala Abdallah, Laura Mahdi, Vita Giordano, Ahmad Daher, Fatima Shamesseddin, Ghassan Ghssein, Nicoletta Resta, Agostino Di Ciaula, Alessandro Stella e Piero Portincasa,
published in the European Journal of Internal Medicine (2026).
