From the Guidelines
MEFV heterozygotes should be treated with colchicine if they experience symptoms, starting at a dose of 0.6 mg once or twice daily, with adjustments based on symptom control and side effects, as recommended by the EULAR guidelines 1. The management of MEFV heterozygotes involves a comprehensive approach, considering the potential for developing Familial Mediterranean Fever (FMF) symptoms, the role of colchicine in treatment, and the importance of genetic counseling.
- MEFV heterozygotes may experience milder symptoms or remain asymptomatic, but some can develop FMF-like symptoms including recurrent fevers, abdominal pain, chest pain, and joint inflammation.
- Colchicine is the standard treatment for symptomatic MEFV heterozygotes, with a typical starting dose of 0.6 mg once or twice daily, which can be adjusted based on symptom control and side effects, with a maximum recommended dose usually being 2.4 mg daily 1.
- The EULAR recommendations emphasize the importance of treating FMF to prevent clinical attacks and minimize subclinical inflammation, with the ultimate goal of improving quality of life and preventing long-term complications such as amyloid A (AA) amyloidosis 1.
- Regular monitoring for side effects such as gastrointestinal issues and rare complications like myopathy or myelosuppression is crucial, and genetic counseling may be beneficial for MEFV heterozygotes, especially when family planning is considered, given the 50% chance of passing the mutation to offspring if the other parent is unaffected.
- The EULAR guidelines also recommend that FMF should be diagnosed and initially treated by a physician with experience in FMF, and that patients should be reviewed by a physician with experience of FMF at least once per year in the long term 1.
From the Research
MEFV Heterozygote
- The MEFV gene is associated with familial Mediterranean fever (FMF), an autosomal-recessive inherited inflammatory disease 2.
- Heterozygous patients with MEFV mutations may exhibit a range of clinical features, including fever, abdominal pain, arthralgia, chest pain, and erysipelas-like lesions 2.
- The most frequent MEFV mutations in heterozygous patients are M694V, E148Q, V726A, and M680I 2.
- Regular colchicine treatment is effective in approximately 83% of heterozygous patients with MEFV mutations 2.
- However, some patients may not respond to colchicine treatment, and alternative therapies such as anti-IL-1 agents (e.g., anakinra) may be effective in reducing attack frequency and improving quality of life 3, 4, 5, 6.
Clinical Features and Treatment Response
- Heterozygous patients with MEFV mutations may experience a range of clinical features, including:
- Treatment with anti-IL-1 agents (e.g., anakinra) has been shown to be effective in reducing attack frequency and improving quality of life in patients with FMF who are unresponsive to colchicine treatment 3, 4, 5, 6.
- Anakinra treatment has been associated with significant improvements in attack frequency, disease severity, and quality of life in patients with FMF 3, 5.