Familial Mediterranean Fever in Pediatric Age
Introduction to Familial Mediterranean Fever in Pediatric Age
Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disorder characterized by recurrent episodes of fever and serositis. It primarily affects populations of Mediterranean descent, including Sephardic Jews, Armenians, Turks, and Arabs. FMF is caused by mutations in the MEFV gene, which encodes the pyrin protein involved in regulating inflammation.
In pediatric patients, FMF typically manifests before the age of 20, with a significant proportion experiencing their first attack in childhood. Early diagnosis and treatment are crucial to prevent complications and improve quality of life.
Epidemiology of Familial Mediterranean Fever in Children
FMF is most prevalent in populations from the Mediterranean basin:
- Incidence: 1/200 to 1/1000 in high-risk populations
- Carrier frequency: Up to 1 in 5 in some ethnic groups
- Age of onset: 90% of patients present before age 20
- Gender distribution: Slightly more common in males
While traditionally associated with specific ethnic groups, FMF is increasingly recognized worldwide due to global migration and improved genetic testing.
Pathophysiology of Familial Mediterranean Fever
FMF is caused by mutations in the MEFV gene, which encodes the pyrin protein. Key aspects of the pathophysiology include:
- Pyrin inflammasome dysregulation: Mutated pyrin leads to uncontrolled activation of the inflammasome complex.
- Excessive IL-1β production: Activated inflammasomes trigger overproduction of pro-inflammatory cytokine IL-1β.
- Neutrophil activation: IL-1β promotes neutrophil recruitment and activation in affected tissues.
- Serosal inflammation: Recurring inflammation affects serosal surfaces, causing typical FMF symptoms.
Understanding this pathophysiology is crucial for developing targeted therapies and managing the disease effectively in pediatric patients.
Clinical Presentation of FMF in Pediatric Patients
FMF attacks in children typically last 12-72 hours and may include:
- Fever: High-grade, recurrent fever is the hallmark symptom
- Abdominal pain: Severe pain mimicking acute abdomen
- Chest pain: Pleuritic pain due to serositis
- Joint pain: Typically monoarthritis affecting large joints
- Skin manifestations: Erysipelas-like erythema, usually on lower extremities
In children, attacks may be less severe or atypical compared to adults. Some patients may experience prodromes before full-blown attacks.
Diagnosis of Familial Mediterranean Fever in Children
Diagnosis of FMF in pediatric patients is based on:
- Clinical criteria: Tel-Hashomer criteria or more recent pediatric-specific criteria
- Genetic testing: Identification of MEFV gene mutations
- Family history: Especially in high-risk ethnic groups
- Response to colchicine: Therapeutic trial can support diagnosis
Laboratory findings during attacks may include elevated acute phase reactants (CRP, ESR, fibrinogen). Between attacks, these markers typically normalize. Genetic testing should be interpreted cautiously, as some patients with clinical FMF may not have identifiable mutations.
Treatment of FMF in Pediatric Patients
Management of FMF in children focuses on preventing attacks and complications:
- Colchicine: First-line therapy, typically 0.5-2 mg/day based on age and weight
- IL-1 inhibitors: For colchicine-resistant or intolerant cases (e.g., anakinra, canakinumab)
- NSAIDs: For symptomatic relief during attacks
- Lifestyle modifications: Stress reduction, adequate hydration, and balanced diet
Regular monitoring of treatment efficacy, side effects, and growth parameters is essential. Genetic counseling should be offered to families.
Complications of Familial Mediterranean Fever in Children
Potential complications of FMF, especially if untreated, include:
- Amyloidosis: Most serious complication, leading to renal failure
- Growth retardation: Due to chronic inflammation
- Joint damage: From recurrent arthritis
- Infertility: Particularly in females with untreated disease
- Psychological impact: Chronic pain and unpredictable attacks can affect mental health
Early diagnosis and appropriate treatment significantly reduce the risk of these complications in pediatric patients.
Prognosis of FMF in Pediatric Patients
With proper management, the prognosis for children with FMF is generally good:
- Most patients respond well to colchicine, with reduced attack frequency and severity
- Risk of amyloidosis is significantly decreased with regular treatment
- Normal life expectancy can be achieved with adherence to therapy
- Quality of life improves with appropriate management and support
Long-term follow-up is crucial to monitor for complications and adjust treatment as needed. Transition of care from pediatric to adult services should be planned carefully.
Familial Mediterranean Fever in Pediatric Age
- What is Familial Mediterranean Fever (FMF)?
An autosomal recessive autoinflammatory disorder characterized by recurrent fevers and serositis - Which gene is mutated in FMF?
MEFV gene (Mediterranean Fever gene) - What is the function of the protein encoded by the MEFV gene?
Pyrin, involved in regulating inflammation and innate immunity - Which ethnic groups are most commonly affected by FMF?
People of Mediterranean descent (Sephardic Jews, Armenians, Turks, and Arabs) - What is the typical age of onset for FMF?
Before 20 years of age, often in early childhood - What is the characteristic feature of fever in FMF?
Recurrent, self-limited episodes lasting 12-72 hours - Which body cavities are commonly affected by serositis in FMF?
Peritoneum, pleura, and synovium - What is the most common symptom of FMF?
Abdominal pain due to peritonitis - Which skin manifestation is characteristic of FMF?
Erysipelas-like erythema, typically on the lower legs - What is the typical duration of an FMF attack?
1-3 days - Which laboratory findings are characteristic during an FMF attack?
Elevated acute phase reactants (ESR, CRP, fibrinogen, and serum amyloid A) - What is the gold standard for diagnosing FMF?
Genetic testing for MEFV mutations - Which diagnostic criteria are commonly used for FMF?
Tel Hashomer criteria or the more recent Eurofever/PRINTO classification criteria - What is the first-line treatment for FMF?
Colchicine - What is the primary goal of colchicine therapy in FMF?
Prevention of attacks and development of amyloidosis - Which complication is the most serious long-term consequence of untreated FMF?
AA amyloidosis - What percentage of untreated FMF patients develop amyloidosis?
Approximately 60-80% if left untreated - Which organ is most commonly affected by amyloidosis in FMF?
Kidneys - What is the role of biological agents in FMF treatment?
Used in colchicine-resistant or intolerant cases, particularly IL-1 inhibitors - Which IL-1 inhibitor has been approved for colchicine-resistant FMF?
Canakinumab - What is the recommended colchicine dosage for children with FMF?
0.5-2 mg/day, adjusted based on age and response - Which type of arthritis can occur in FMF?
Acute monoarthritis, typically affecting large joints - What is the role of genetic counseling in FMF?
Important for family planning and screening of relatives - Which cardiac complication can occur in FMF?
Pericarditis - What is the prognosis for children with FMF who are adequately treated?
Generally good, with normal life expectancy if amyloidosis is prevented - Which factor can trigger FMF attacks?
Stress, menstruation, fatty meals, or extreme temperature changes - What is the role of SAA (Serum Amyloid A) monitoring in FMF management?
Used to assess subclinical inflammation and risk of amyloidosis - Which imaging modality can be used to diagnose acute abdominal attacks in FMF?
Ultrasound or CT scan - What is the impact of FMF on growth and development in children?
Can lead to growth retardation if not adequately treated
