Introduction
FMF is an autoinflammatory genetic disorder causing inflammation of the abdomen, lungs, and joints. This condition occurs before the age of 20 years. The first attack is found to appear in childhood. Sometimes, it may occur with a rash or headache. It is a hereditary disorder affecting people of Mediterranean and Middle Eastern origin. The characteristic of this condition is periodic fever syndrome.
What Is FMF?
FMF is a rare disease occurring throughout the world. It can affect individuals of Sephardic Jewish, Armenian, Arab, and Turkish heritage. The availability of genetic testing has been a help in identifying more people with such a condition with Mediterranean roots, including Ashkenazi Jews, Italians, Greeks, Spaniards, and Cypriots, and occasional cases may be found in other ethnicities. The condition may affect one in 200 to 1000 people in this population.
This condition exhibits recurrent inflammation with fever due to a defect in the immune system. The other name of this condition is hereditary periodic fever syndrome. Anyone may be affected by this condition without discrimination of gender.
What Are the Causes of FMF?
FMF is caused mainly due to the mutation of a gene called MEFV.The affected children receive copies of faulty genes from both parents. Some children may develop the same symptoms even though only one gene is inherited from one of the parents. It was noticed that MEFV mutations are of 300 types but very few may lead to FMF.
It was observed that MEFV is responsible for making a protein called pyrin. Pyrin is considered important for the functioning of the immune system. When a mutation of MEFV occurs, it cannot produce sufficient protein called pyrin. This may affect the immune system, and there is an increased production of inflammatory cytokines called interleukin 1B. This may further lead to inflammation and fevers.
A gene called SAA1 can modify the course of FMF. Studies have observed that a particular variant of the SAA1 gene, especially the alpha variant, increases the risk of amyloidosis among those with FMF.
What Are the Symptoms of FMF?
The symptoms of FMF begin at the ages of 5 and 15 years. Inflammation of the lining of the abdominal cavity, chest cavity, skin, or joints with high-grade fever that may rise in 12 to 24 hours may be observed. The symptoms occur in bouts called attacks that may last for one to three days. Arthritic attacks may last for weeks or months. People affected are found to be symptom-free in between the attacks.
The symptoms of FMF include:
-
Experience abdominal pain.
-
The chest pain experienced is sharp and becomes worse while taking a breath.
-
Experience fever or fever and chills alternatively.
-
Joint pain is observed.
-
Skin sores that appear red and swollen and 5 to 20 cm in diameter.
-
Experience constipation followed by diarrhea.
-
Muscle pain may be observed.
-
Pericarditis (tissue inflammation around the outside of the heart) may be observed.
-
Meningitis (Inflammation of the tissue around the brain and spinal cord).
-
Inflammation of the testicles may be observed.
-
The spleen gets enlarged.
-
Amyloidosis (protein buildup in urine) may be caused, and this can lead to kidney damage.
What Are the Atypical Presentations of FMF?
The symptoms of FMF differ from one to another, even in the same family. The repeated attacks occur without warning signs and may remain for one to four days. Attacks get triggered by weakness, stress, and physical activities.
-
Repeated fevers may be experienced among children ranging from 100 to 104 degrees Fahrenheit. It may be associated with other symptoms or may occur alone.
-
Inflammation of serous tissues (membranes of the abdomen, lung, and heart) may be observed. It is also known as serositis.
-
Abdominal symptoms may be from bloating to inflammation of the lining of the abdomen, known as peritonitis. The symptoms related to the abdomen include
-
Pain in the abdomen.
-
Abdominal muscles become rigid and tight, and they appear board-like.
-
The abdomen may become swollen or distended.
-
Abdominal symptoms may accompany constipation, and diarrhea may appear after the attack ends.
-
The joint pain and inflammation may be observed due to the inflammation of the lining of the joints (synovium).
-
The joint pain may be severe, and swelling may be observed.
-
During the attack, the movements of joints should be minimal. The attacks of inflammation of joints (arthritis) may occur suddenly and may last for seven days.
-
The attacks of joint pain may be due to minor trauma or sustained exertion like prolonged walking.
-
The attacks most often involve large joints like the knee, ankle, or hip.
-
-
The chest pain may be due to inflammation of the lining of the lungs (pleuritis).
-
The attacks may begin suddenly and last for 48 hours.
-
Affected individuals experience painful breathing and decreased breathing sounds.
-
Shortness of breath and rapid, shallow breathing may be observed.
Other symptoms or presentations include:
Erysipelas: Painful, swollen, and bright red lesions may appear on the lower legs, similar to erysipelas. These lesions are warm or hot to the touch and usually appear between the ankle and the knee.
Pericarditis: Pericarditis (inflammation of the heart's lining) may occur. This may be associated with pain in the sternum and this may worsen during swallowing.
Meninges and Meningitis: Headaches may appear due to inflammation of the membrane (meninges) lining the brain and the spinal cord (meningitis).
Myalgia: Muscle pain is observed as severe and widespread (diffuse).
-
Myalgia may be associated with other symptoms.
-
Myalgia attacks may last for short or longer periods.
Spleenomegaly: Spleenomegaly (enlarged spleen) may be observed among children.
Amyloidosis: Serious complications known as amyloidosis may develop among the few affected by FMF. Amyloidosis is a condition in which deposition of amyloid a fatty-like substance may occur in different parts of the body.
Orchitis: Orchitis may occur which is an inflammation of the testes. Redness, swelling, and pain may be observed in the testes.
Vasculitis: Inflammation of blood vessels, known as vasculitis, may be observed. These may include Bechet’s disease, polyarteritis nodosa, and Henoch-Schonlein purpura. Affected with FMF may exhibit an increased risk for ulcerative colitis, Crohn’s disease, and rheumatoid arthritis. Atypical meningitis involves chronic aseptic meningitis.
Conclusion
Familial Mediterranean Fever is a genetic disorder caused due to mutations of genes. It causes inflammation of various organs of the body. Joint pains are also common to occur. Many complications of this disorder can be observed. Hence, it is important to know about FMF, its causes, and atypical and typical presentations.
