Familial Mediterranean Fever Page 1 of 12 Familial Mediterranean fever • Is a hereditary autoinflammatory disorder characterized by recurrent bouts of fever and serosal inflammation. • The initial attack occurs before the ages of 10 and 20 years in 65 and 90 percent of cases. • In rare cases, the initial attack can occur in individuals older than 50 years of age. • As the name indicates, FMF occurs within families and is much more common in individuals of Mediterranean descent than in persons of any other ethnicity Epidemiology In adults, FMF is more prevalent in men than in women. • It mainly occurs in families of Mediterranean area. • Age: 50-60% are younger than 10 years. 80-95% are younger than 20 years. 5-10% are older than 20 years at onset. • Onset in people older than 40 years is rare Pathophysiology • Mutations in the MEFV (Mediterranean fever) gene on chromosome 16 appear to cause the disease in many cases. MEFV produces a protein called pyrin (derived from the association with predominant fever); the protein is also called marenostrin (derived from the phrase "our sea," because of the Mediterranean heritage of most patients). • Pyrin acts without a known provocation, the outcome of this process is secretion of interlukin IL-1,IL-18 and other mediators of inflammation which enhances chemotaxis and neutrophilia including an attack of FMF leading to episodes of inflammation (with accompanying fever) in the peritoneum, pleura, and joints; persistent subclinical inflammation is also common. • The inflammatory episodes in persons with FMF lead to the excess production of amyloid A protein in the acute phase and reactant serum amyloid A with subsequent deposition in the kidneys. Only patients with specific MEFV haplotypes develop amyloidosis.
12
Embed
Familial Mediterranean fever...Familial Mediterranean Fever Page 1 of 12 Familial Mediterranean fever • Is a hereditary autoinflammatory disorder characterized by recurrent bouts
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Familial Mediterranean Fever
Page 1 of 12
Familial Mediterranean fever
• Is a hereditary autoinflammatory disorder characterized by recurrent bouts of
fever and serosal inflammation.
• The initial attack occurs before the ages of 10 and 20 years in 65 and 90 percent
of cases.
• In rare cases, the initial attack can occur in individuals older than 50 years of age.
• As the name indicates, FMF occurs within families and is much more common in
individuals of Mediterranean descent than in persons of any other ethnicity
Epidemiology In adults, FMF is more prevalent in men than in women.
• It mainly occurs in families of Mediterranean area.
• Age:
50-60% are younger than 10 years.
80-95% are younger than 20 years.
5-10% are older than 20 years at onset.
• Onset in people older than 40 years is rare
Pathophysiology
• Mutations in the MEFV (Mediterranean fever) gene on chromosome 16 appear
to cause the disease in many cases. MEFV produces a protein called pyrin
(derived from the association with predominant fever); the protein is also called
marenostrin (derived from the phrase "our sea," because of the Mediterranean
heritage of most patients).
• Pyrin acts without a known provocation, the outcome of this process is secretion
of interlukin IL-1,IL-18 and other mediators of inflammation which enhances
chemotaxis and neutrophilia including an attack of FMF leading to episodes of
inflammation (with accompanying fever) in the peritoneum, pleura, and joints;
persistent subclinical inflammation is also common.
• The inflammatory episodes in persons with FMF lead to the excess production of
amyloid A protein in the acute phase and reactant serum amyloid A with
subsequent deposition in the kidneys. Only patients with
specific MEFV haplotypes develop amyloidosis.
Familial Mediterranean Fever
Page 2 of 12
Clinical manifestations
• Episodes last for one to three days and then resolve spontaneously
• The intervals between episodes are irregular, ranging from one week to several
months or years, and patients are asymptomatic between attacks.
• Patients may have a stereotypic prodrome before their attacks; it may include
various constitutional and physical signs, such as restlessness at the site where the
symptom is about to occur, anxiety, irritability, increased appetite, and taste
alterations.
• vigorous exercise, emotional stress, intercurrent infections, exposure to cold,
surgery, and menstruation have been associated with an attack in some patients
• During pregnancy, the course of FMF may worsen in about a third of the patients,
improve in another third of patients, and remain unchanged in the rest.
1) Recurrent fever:
• It is one of the most constant characteristics, presents in almost all cases during
attacks (38° to 40°C), the duration is brief, lasting between 12 hours and three
days
• It may be the first and only symptom of FMF, especially in toddlers.
• FMF patients who are treated with colchicine, an acute attack may occur without
fever.
2) Abdominal pain
• It occurs in 95% in patients, presents locally and then progress to become more
generalized.
• It is caused by inflammation of the peritoneum, signs of peritonitis such as
guarding; rebound tenderness, rigidity, and a dynamic ileus are often present.
• These findings can be mistaken for an acute surgical abdomen leading to
diagnosis delay and sometimes even to futile operations.
3) Chest pain:
• It occurs in 33-84 %of patients, depending on the patient’s ethnic origin.
(Armenian have a higher rate of pleuritic involvement compared with other ethnic
groups).
Familial Mediterranean Fever
Page 3 of 12
• May be due to inflammation of the pleura or referred pain from subdiaphragmatic
inflammation.
• Manifests as unilateral chest pain that is worse with inspiration or coughing and
small, transient pleural effusion.
• Episodes usually resolve within three days, but may last up to one week.
4) Joint pain
• The joint attacks are usually monoarticular, involving one of the large joints
(knee, ankle, hip)
• The synovial fluid analysis is typically sterile, with a nucleated white cell count
ranging from 200 to >100,000 white blood cells/mm3
• episodes usually lasts 24 to 48 hours, which resolve completely without leading to
joint destruction, but in severely protracted cases, it can result in permanent
deformity, functional limitation, osteoporosis around the affected joint, and
aseptic necrosis.
5) Erysipelas-like skin lesion:
• It occurs in 12 to 40%
• The lesion is typically 10 to 35 cm2 in area, tender, raised, and erythematous and
occurs on the lower leg, ankle, or foot.
• Lesions may be transiently warm without associated pain or tenderness
• In children, it may be misdiagnosed as an infectious erysipelas or cellulitis.
• Recovery is spontaneous and does not require antibiotics
Other rare manifestations:
• Exertional myalgia: involves lower limbs (thighs and calves) in children, not
treated by colchicine, resolves with rest and NSAIDs
• Acute pericarditis: include chest pain (sharp and pleuritic, improved by sitting
up and leaning forward), pericardial friction rub, and widespread ST segment
elevation on electrocardiogram
Familial Mediterranean Fever
Page 4 of 12
• Acute scrotum: unilateral gradual swelling of the scrotum in children.
• Protracted febrile myalgia: have an increased ESR but a normal serum creatine
kinase level
• Headache and aseptic meningitis.
Long-term complications:
• Secondary (AA) amyloidosis
• Small bowel obstruction
• Infertility
DIAGNOSIS:
• FMF is suspected in individuals with recurrent febrile episodes accompanied by
peritonitis, synovitis or pleuritis, recurrent erysipelas-like erythema, repeated
laparotomies for an acute abdomen with no identifiable underlying pathology, a
first-degree relative with FMF, and/or membership in an at-risk ethnic group.
• Genetic testing for FMF serves to support the diagnosis in patients who meet
clinical criteria for FMF
• Six-month trial of colchicine therapy that results in a relief of attacks and
recurrence after cessation of treatment. (In patients who met the clinical criteria
but genetic testing was not diagnostic).
FMF is diagnosed in patients with any of the following:
• ≥1 major criteria
• ≥2 minor criteria
Elevation of serum markers of systemic
inflammation
Elevated erythrocyte sedimentation rate
(ESR)
Elevated C-reactive protein (CRP)
Elevated serum amyloid A (SAA)
protein
Elevated fibrinogen.
Serum homocysteine and lipoprotein(a)
Familial Mediterranean Fever
Page 5 of 12
• 1 minor plus 5 supportive criteria
• 1 minor criterion plus ≥ 4 of the first
five supportive criteria
Differential diagnosis:
* It varies with the patient's predominant clinical features