Familial Mediterranean fever FMF

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Familial Mediterranean fever (FMF)

• DR.NIZAR ALHARBAT
• CONSALTANTE OF PEDIATRIC
• ARAB BORD

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PATTERN OF INHERITANCE

• Autosomal recessive trait
• FMF is most prevalent in individuals of
• Sephardic Jewish (1 in 6 8 )
• Armenian (1 in 7 )
• Ashkenazi (1 in 12 )
• Turkish
• Arab descent

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The FMF gene ( MEFV )

• MEFV is located on the short arm of chromosome 16
• MEFV encodes a 781 amino acid protein
• Sites, 694 and 726, are widely distributed.
• M694V is more severe than that of V726A
• at least 23 mutations have been identified .

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CLINICAL MANIFESTATIONS

• The initial attack occurs before the age of 10 in
  65 , and in 90 before the age of 20 .
• The typical manifestations of the disease are
  recurrent attacks of severe pain and fever,
  lasting one to three days, and then resolving
  spontaneously.
• In between attacks, patients feel entirely well.

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CLINICAL MANIFESTATIONS

• Pain and fever are usually abrupt and reach their
  peak soon after onset
• The frequency of attacks is highly variable
• Vigorous exercise is regarded as an attack
  trigger by a few patients
• Attacks tend to abate during the second half of
  pregnancy

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CLINICAL MANIFESTATIONS (Peritonitis )

• 95 of patients with FMF have painful attacks
  localized to the abdomen
• Pain and tenderness may initially be focal, and
  then progress to become more generalized
• Guarding, rebound tenderness, rigidity, and an
  adynamic ileus are often present
• Recurrent attacks of peritonitis may lead to
  adhesions, with the potential for causing small
  bowel obstruction

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CLINICAL MANIFESTATIONS (Pleuritis )

• Painful FMF attacks may also be localized to the
  chest.
• They may reflect either direct inflammation of
  the pleura or referred pain from subdiaphragmatic
  inflammation .
• Pleural inflammation typically manifests as
  unilateral pleuritic chest pain with a small,
  transient pleural effusion .
• These episodes usually resolve within three days,
  but may last up to one week.

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CLINICAL MANIFESTATIONS (Synovitis)

• Arthritis is another common manifestation of FMF
  .
• Its incidence correlates with the patient's
  ethnicity.
• The arthritis is most often monoarticular or
  oligoarticular .
• The joints most often affected are the knee,
  ankle, hip, and elbow, in order of frequency.

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CLINICAL MANIFESTATIONS (Synovitis)

• Joint effusions are common during attacks of
  synovitis.
• The arthritis often occurs independently of the
  other manifestations of FMF, and may last for
  weeks to months.
• The synovitis usually resolves completely without
  joint destruction.

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CLINICAL MANIFESTATIONS Other acute
manifestations

• Pericarditis has been described in several
  patients with FMF ( 0.7 )
• Self-limited orchitis and recurrent aseptic
  meningitis also can occur.
• A few patients with FMF have reported protracted
  bouts of febrile myalgia that may last as long as
  one month, and sometimes involve the abdominal
  muscles .
• An enhanced incidence of some vasculitides, such
  as polyarteritis nodosa and Henoch-Schonlein
  purpura, has been described .

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DIAGNOSIS

• The cloning of the FMF gene in 1997 makes genetic
  testing possible .
• currently available genetic tests do not assess
  for all mutations associated with FMF
• the diagnosis can be made upon clinical grounds
  and rests upon both the characteristic clinical
  features and the exclusion of other illnesses.

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DIAGNOSIS

• The three major findings are
• Intermittent episodes of fever
• Concomitant serositis
• Absence of an alternative cause

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DIAGNOSIS

• The following findings may or may not be present
• Amyloidosis
• Positive family history
• Mediterranean ancestry
• Responsiveness to colchicine

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Diagnostic criteria
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Diagnostic criteria
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DIAGNOSIS

• Other proposed tests for FMF
• metaraminol provocation test .
• measurement of the serum concentration of
  dopamine beta-hydroxylase (DBH).

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Differential diagnosis

• 1 - Surgical emergencies appendicitis,
  intussusception,
  perforated peptic ulcer, etc.
• 2 - Hereditary angioedema
• 3 - Acute intermittent porphyria
• 4 - Relapsing pancreatitis
• 5 - Systemic lupus erythematosus and
  vasculitis
• 6 - Hypertriglyceridemia
• 7 - Abdominal epilepsy and abdominal migraine
• 8 - Other rare hereditary periodic fevers
  tumor necrosis factor receptor-1-associated
  periodic syndrome (also called TRAPS), hyper-IgD
  syndrome, Muckle-Wells syndrome, and familial
  cold autoinflammatory syndrome .

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Therapy

• Therapy for FMF are twofold
• Symptomatic relief from the acute attacks
• Prevention of the development and
• progression of amyloidosis

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Therapy ( COLCHICINE )

• Colchicine is a cheap, effective, and safe way of
  managing FMF when used as a continuous,
  preventive therapy.
• The dose is 0.6 mg PO BID (TID, rarely QID )
• Patients who already have significant proteinuria
  should receive a dose of 1.5 to 2.0 mg/day.

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Therapy

• For the few patients who are not benefited by
  colchicine , several approaches can be tried
• interferon alpha (single dose 3 to 10 million
  I.U. s.c )
• alpha blocker prazosin (3 mg BID)
• Adhering to a very low fat diet

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PREVENTION OF AMYLOIDOSIS WITH COLCHICINE

• Among untreated patients with FMF, AA amyloidosis
  has been found to occur with variable frequency,
  depending upon the ethnic origin of the patient
  (Turkish 60 , non-Askenazi Jews 30 , Armenians
  2 )
• Colchicine, as preventive therapy, can markedly
  reduce the incidence of clinical renal disease
  and stabilize the glomerular filtration rate in
  patients with mild proteinuria
• Among FMF patients with the nephrotic syndrome,
  prevention of disease progression and a reduction
  in protein excretion can be achieved (1.5 to 2.0
  mg/day )

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PREVENTION OF AMYLOIDOSIS WITH COLCHICINE

• Colchicine is not likely to be effective in
  patients who already have chronic renal failure .
• It can prevent recurrent disease (as manifested
  by proteinuria) in the transplant .
• The optimal colchicine dose in this setting is
  1.5 to 2.0 mg/day lower doses are less
  predictably effective.

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• Assalam Aleekum