Dr. Müge Bıçakçıgil Kalaycı

Familial Mediterranean fever(FMF)

Familial Mediterranean feverRecurrent, short-lived episodes of fever

accompanied by peritoneal, pleural, or arthritic inflammation.

the mechanisms leading to the clinical manifestations of the disease are still unknown

The inheritance of familial Mediterranean feverThe disease may become manifest as early

as during the first year of life, although in most cases onset is later.

In two-thirds of patients the first manifestations appeared during the first decade of life; by the end of the second decade 90 per cent are affected.

Only rarely is the onset delayed beyond the age of 40.

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

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 .

AttacksThe febrile, painful attacks that are the

hallmark of the disease are characterized by; marked elevation of body temperature, acute inflammation of the peritoneum,

synovia, or pleura, a duration of 12 to 48 h, and complete health between attacks .Repeated attacks at irregular intervals and in

an unpredictable sequence

Abdominal attackThe most frequent manifestation experienced by 90 per cent of patients They are marked by the sudden onset of fever

(often with chills) Pain spreading over the entire abdomen from

variable points of origin.Guarding, rebound tenderness, board-like

rigidity, distension, and absence of peristalsis appear.

Multiple, small fluid levels in the small bowel on radiography

Suggest an acute abdominal catastrophe.

Abdominal attackAfter 6 to 12 h the signs and symptoms

recede, and within 24 to 48 h the attack is usually over, leaving the patient as well as before.

Organization of the exudate may result in fibrous adhesions, mechanical ileus sterility in some affected women .

pleural attack45 % of patients, and in 5 % it was the

presenting sign .abrupt onset, rapid resolution, and

unpredictable recurrence. Breathing is painful and breath sounds are

diminished on the affected side. small exudate in the costophrenic angle,

which is difficult to aspirate and which resolves within 48 h.

Pericarditis-a rare feature of familial Mediterranean

fever.No permanent sequelae have been reported.

Muscle pains (20%)lasts from a few hours to 1 to 2 days, and subsides with rest or non-steroidal anti-

inflammatory drugs.

articular attackthe second most common form of attack.

(75%)Arthritic attacks may recur for years as the

only feature of the disease, before other forms appear .

Large joints are involved, particularly those of the lower extremities.

In two forms: acute, or chronic and protracted.

In the acute form:

the onset is abrupt, fever ranges from 38 to 40°C, and the affected single joint is tender, swollen, and

held immobile The signs and symptoms usually peak in 1 to 2

days and then gradually subside, leaving no residue.

The attacks can sometimes be precipitated by minor trauma or effort, such as prolonged walking. Synovial effusion is often demonstrable.

Resolution of a short attack can occur in as soon as 2 to 3 days, but more commonly takes a week and sometimes nearly a month.

Chronic-protracted attacks (5%)persist for more than a month. Usually the hip or knee are involved , the joint remains markedly swollen and painful,

presenting a picture of chronic monoarthritis or chronic oligoarthritis.

After several weeks or months, sometimes even after a year or more, the pain subsides spontaneously.

During such protracted attacks in a joint, short attacks involving other joints, the abdomen, or chest may occur .

   

Erysipelas-like erythema (11%)one of the most characteristic manifestations

of FMF. usually combined with arthritis.Rather sharply bordered red patches, hot,

tender, and swollen, and 10 to 35 cm2 in area, appear on the skin of the lower extremities.

They are usually located between the knee and ankle, or on the dorsum of the foot or ankle region, and are also accompanied by abrupt elevation of body temperature and last about 24 to 48 h .

Orchitis an acute, unilateral, painful swelling and

redness of the testis it subsides spontaneously after 12 to 24 h,

without anatomical residue .

Mild splenomegaly of 1 to 4 cm, unrelated to amyloidosis.

Haematuria, sometimes only microscopic.

Amyloidosis is major cause of mortality in FMF.

Tel-Hashomer Diagnostic criteria

 Major criteria 1.Painful inflammatory manifestations in the

abdomen, chest, joints, or skin, associated with the fever.

2.Nephropathic amyloidosis.3.Dramatic response to continuous colchicine

treatment in abolishing or reducing febrile attacksMinor criteria4.Short attacks of fever recurring at irregular

intervals.5. Family history6. Erysipelas like rash

Diagnosis- 2 major or 1 major 2 minor criteria

Laboratory findingsnon-specific. The erythrocyte sedimentation rate is

accelerated and acute-phase proteins such as a2-globulin

and fibrinogen are increased, especially during attacks, but also in between

Leucocytes increasedCrp and ESR elevated

Laboratory findingsSerum amyloid A is raised

acute-phase protein

the familial Mediterranean fever (FMF) gene located on the short arm of chromosome 16

Treatment-to prevent attacksDaily prophylactic treatment with colchicine Treatment is started with 1 mg

colchicine/day, regardless of age or severity of attacks.

This dose is increased if necessary to 1.5 to 2 mg, until remission from attacks is achieved.

Continuous prophylactic treatment with colchicine in patients inhibits the development of nephropathic amyloidosis

.