Fiebre mediterránea familiar - Hoogstra

Contents

What is it family Mediterranean fever?

Familial Mediterranean fever is hereditary autoinflammatory syndrome characterized by recurrent short episodes of high fever associated with abdominal pain, inflammation of joints and other sites of the body and skin eruption. If left untreated, amyloidosis commonly develops and can be fatal. Familial Mediterranean fever is the most common periodic fever syndrome.

In familial Mediterranean fever type 2, amyloidosis is the presenting feature without a history of typical symptoms. febrile episodes

Who gets familial Mediterranean fever and why?

Familial Mediterranean fever primarily affects specific racial groups originating throughout the eastern Mediterranean Sea. These include:

Arabs
Armenians
Italians (mild form)
Jews
Turks

In these groups, 1 in 25 to 1 in 2,000 people are affected. In comparison, in Western Europeans, the predominance is 2.5 per 100,000 (1 in 40,000) people. the carrier the rate can be as high as 1 in 3 in some groups. Although previously believed to only affect Sephardic Jews, it has recently been recognized that Ashkenazi Jews suffer from a mild form of the syndrome. Two-thirds of patients develop symptoms before the age of 5 years and 90% within 20 years.

Familial Mediterranean fever is usually inherited as a autosomal recessive condition, meaning both parents must carry the defect gene and there is a one in four chance that a child will be affected (MIM 249100). There is a less common autosomal dominant form (MIM 134610).

Molecular biology and genetics

Familial Mediterranean fever is usually due to mutations in Mediterranean feverMEFV) or pyrin gene located in chromosome 16 (16p13.3). Mutations in the MEFV gene have been found in the 80% of typical cases. More than 100 different mutations related to the disease have been identified. The most commonly reported mutation, M694V, is associated with severe disease and the development of secondary amyloidosis. Other common mutations are M680I and V726A. 20% of the Ashkenazy Jews carry the E148Q MEFV mutation.

the MEFV genetic codes for a protein called pyrin (also known as marenostrin) expressed primarily by inflammatory white blood cells like neutrophils and eosinophils. The normal form of pyrin suppresses inflammation by downregulating pro-inflammatories. cytokines (cellular messenger proteins), positive regulation of anti-inflammatory cytokines and the prevention of the production of interleukin 1beta (IL-1β) by inflammasomes. Lack of functional pyrin releases the inflammatory cascade.

There are also environmental effects on the manifestations of familial Mediterranean fever. For example, Armenians with familial Mediterranean fever residing in Armenia have a incidence of amyloidosis from 25 to 48%, while Armenians residing in the US have an incidence of amyloidosis from 0%.

What are the clinical characteristics of familial Mediterranean fever?

The most common clinical characteristics of familial Mediterranean fever are:

febrile attacks that last 1 to 3 days
severe abdominal, chest and/or joint pain
Erysipelas-like changes in the lower legs.

The onset is almost always before 30 years of age. Children younger than 2 years often present with fever alone and progress to more typical attacks by the age of 5 years.

The characteristics of the recurring acute Familial Mediterranean fever episodes are described in the table below.

Symptom	Characteristics
Fever	high, sharp lasts 1-3 days
Abdominal pain	affects 95% due to inflammation of the linings of the abdominal cavity (peritonitis) severe muscle stiffness, board-like, rebound tenderness associated constipation or diarrhea can mimic symptoms and signs of appendicitis
Chest pain	affects 33-50% due to inflammation of the lining around the lungs (pleuritis) associated with shortness of breath or shallow breathing less commonly due to the inflamed sac around the heart (pericarditis, 1%)
Pain and swelling in the joints (arthralgia, arthritis)	affect up to 75% due to inflammation of the joint lining (synovitis) with neutrophils Arthralgia is common, arthritis is seen in younger patients. Three patterns of arthritis are recognized: asymmetric non-destructive arthritis presenting as swelling of 1-2 large joints, most commonly ankles, knees or wrists chronic destructive arthritis migratory polyarthritis
Skin rash	affect 40% various presentations (see below)
Scrotal painorchitis)	affects 5% especially young children
Enlarged spleen (splenomegaly)	especially in children
Muscle pain (myalgia)	most commonly muscle pain in the legs after exercise Rarely, pain and weakness can last for weeks, resulting in an inability to walk (“prolonged febrile myalgia”).
Neurological symptoms	affect 10-15% due to inflammation of the linings around the brain (aseptic meningitis) headache: one series reported 45% in association with febrile episodes abdominal epilepsy Feverish convulsions
Amyloidosis	The biggest complication of FMF can cause kidney or liver failure and death can also result in a peripheral neuropathy

What are the characteristics of the skin rash?

Cutaneous characteristics of familial Mediterranean fever
Erysipelas-type lesions	the most distinctive of skin changes occur in 15-20% of children good-demarcated, warm, red and painful plates commonly on the front of the legs between the ankle and knee, but characteristically the top of the foot or over the medium ankle malleoli up to 15 cm in diameter often associated with joint pain whether it's unilateral or symmetrical
Henoch-Schönlein purple	reported in 5% of children
Non-specific purple	reported in 5% of children seen on the face, trunk and extremities a common finding in children
Polyarteritis nodosa	queer tends to occur at an early age associated with peri-renal hematoma
Angioedema	rarely reported
Redness of the palms	rarely reported
Raynaud's phenomenon	rarely reported

What triggers the attacks?

The frequency of episodes is variable, from weekly to every few years. Attacks can be caused by:

Exercise
Infection
Menstruation
Stress.

Acute attacks occur spontaneously. Between episodes, health is normal.

How is familial Mediterranean fever diagnosed?

The diagnosis of familial Mediterranean fever is made using the Tel-Hashomer criteria:

The diagnosis is definitive if 2 major criteria or 1 major + 2 minor criteria are met.
The diagnosis is probable if 1 major + 1 minor criterion are met.

Main criteria

Recurrent febrile episodes associated with peritonitis, pleuritis or synovitis.
Type AA amyloidosis without a predisposing disease
Favorable response to daily colchicine.

Minor criteria

Recurrent febrile episodes
Erysipelas erythema
A positive history of familial Mediterranean fever in a first-degree relative

Research on familial Mediterranean fever.

Blood tests during an attack can show:

Increased white blood cell count (leukocytosis), erythrocytes sedimentation rate (ESR), serum fibrinogen, C-reactive protein (CRP)
Increased serum IgD in 10%.

X-rays of the abdomen often reveal multiple levels of fluid suggesting an “acute abdomen.”

A skin biopsy erysipelas type injury can show a heavy infiltrate of neutrophils (white blood cells). Leukocytoclastic vasculitis it's seen in biopsies of Henoch-Schönlein purpura or polyarteritis nodosa type lesions.

Investigations for myalgia (muscle pain) reveal normal muscle enzymes, electromyography (EMG) and muscle biopsy.

La amiloidosis se presenta con mayor frecuencia como proteinuria sin glóbulos rojos o presión arterial elevada.

La secuenciación de genes puede ser realizada por laboratorios especializados como análisis de mutaciones específicas (buscando las mutaciones más comunes) o análisis de secuencia de exones seleccionados (observando el exón 10 y posiblemente otros). Una vez que se han identificado las mutaciones genéticas en el paciente, el estado de portador de los padres, la detección de otros parientes consanguíneos de primer grado, incluso si asymptomaticand prenatal El diagnóstico puede ser determinado. La identificación de individuos asintomáticos pero genéticamente afectados significa que se puede comenzar el tratamiento para prevenir el desarrollo de amiloidosis.

What is the treatment of familial Mediterranean fever?

La colchicina, tomada por vía oral todos los días de por vida, es el fármaco de elección para la fiebre mediterránea familiar para:

reducir la frecuencia de los ataques
reducir la gravedad de los ataques
prevenir secundaria systemic amyloidosis.

La colchicina es potencialmente toxic Por lo tanto, es muy importante no tomar una dosis excesiva.

La dosis de colchicina se incrementa gradualmente hasta una dosis máxima de 2.5 mg / día. La dosis generalmente está determinada por la frecuencia y la gravedad de los ataques. La colchicina produce una mejora notable en los síntomas para el 90-95% de los pacientes, y el 75% tiene prácticamente completa remission. No se sabe cómo funciona.

Other treatment

Los ataques agudos se tratan con fármacos anti-inflamatorios no esteroideos (NSAID) y alivio del dolor.

La fiebre prolongada con dolor muscular responde a los corticosteroides sistémicos.

La razón más común para no responder a la colchicina es el mal cumplimiento debido al malestar gastrointestinal. Sin embargo, del 5 al 10% no responde a la colchicina y esto puede deberse a ABCB1 gene polymorphisms afectando la captación de colchicina por las células mononucleares.

Talidomida y agentes biológicos, como diariamente subcutaneous anakinra (una interleucina-1 receiver antagonista) o etanercept, pueden considerarse para prevenir ataques y el desarrollo de amiloidosis. Para reducir la gravedad de un ataque, se ha informado que la dosis única de metilprednisolona o anakinra al comienzo de los episodios alivia los síntomas.

Familial Mediterranean fever