Familial Mediterranean fever

Definition

Familial Mediterranean fever is an inflammatory disorder that causes recurrent fevers and painful inflammation of your abdomen, lungs and joints.

Familial Mediterranean fever (FMF) is an inherited disorder that usually occurs in people of Mediterranean origin — including Sephardic Jews, Arabs, Armenians and Turks. But it may affect any ethnic group.

Familial Mediterranean fever is typically diagnosed during childhood. While there's no cure for this disorder, you may be able to relieve signs and symptoms of familial Mediterranean fever — or even prevent them altogether — by adhering to your treatment.

Symptoms

Signs and symptoms of familial Mediterranean fever usually begin during childhood. In fact, 90 percent of all people initially diagnosed with FMF are younger than 20 years old. The signs and symptoms, which are collectively referred to as attacks, often occur with little warning. Generally, the attacks last two to three days. Typical signs and symptoms of FMF may include:

• A sudden fever, ranging from about 100 F (37.8 C) to 104 F (40 C)
• Abdominal pain
• Recurrent chest pain
• Achy, swollen joints
• Constipation followed by diarrhea (in children, usually just diarrhea)
• A red rash on your legs, especially below your knees
• Muscle aches
• A swollen, tender scrotum

Attacks usually occur sporadically, although some people report that vigorous exercise or stress provokes their attacks. Symptom-free periods may be as short as a week or as long as months. Between attacks, you'll likely feel normal.

When to see a doctor
If you or your child experiences sudden worrisome signs or symptoms, such as shortness of breath or passing out, call 911 or get emergency medical help.

See your doctor if you or your child has a sudden fever accompanied by pain in the abdomen, chest and joints so that the doctor can determine the cause.

Causes

The cause of familial Mediterranean fever is a gene defect on chromosome 16. The gene, called MEFV, carries the genetic code for a protein called pyrin, which is involved in regulating inflammation. More than 50 different mutations in the MEFV gene have been identified. Although it's not certain exactly how this defect causes familial Mediterranean fever, it may be that people with this mutation don't make pyrin, hence, inflammatory responses aren't regulated and may be quite severe.

Familial Mediterranean fever is inherited as an autosomal recessive trait, meaning that you must inherit the mutated gene from each parent in order to develop the condition.

Autosomal recessive inheritance pattern

Autosomal recessive inheritance pattern

To have an autosomal recessive disorder, you inherit two mutated genes, one from each parent. These disorders are usually passed on by two carriers. Their health is rarely affected, but they have one ...

Risk factors

If you're of Mediterranean descent or you have a blood-related relative with familial Mediterranean fever, you're at higher risk of developing the disorder. Men also are more likely to be affected.

Complications

Most complications of familial Mediterranean fever result if the condition isn't treated or if it's treated irregularly. Complications may include:

• Amyloidosis. This is the most common complication arising from untreated familial Mediterranean fever. Amyloidosis refers to a condition in which a protein called amyloid A builds up in your organs. In cases of FMF, amyloidosis often affects the kidneys, which may cause a kidney disorder called nephrotic syndrome.
• Nephrotic syndrome. Nephrotic syndrome, which is usually related to amyloidosis, occurs when your kidneys' filtering systems (glomeruli) are damaged. People with this condition may lose large amounts of protein in their urine. Nephrotic syndrome can lead to blood clots in your kidneys (renal vein thrombosis) or kidney failure.
• Infertility. Inflammation caused by familial Mediterranean fever may also affect your reproductive organs. About one-third of women with this condition are infertile, and about 25 percent of those who become pregnant experience miscarriages.
• Chronic arthritis. Arthritis is common in people with familial Mediterranean fever. The most commonly affected joints are the knee, ankle, hip and elbow. In most cases, the arthritis resolves without joint destruction.
• General discomfort. Familial Mediterranean fever can be a painful condition interfering with the flow of daily life. If your symptoms are intolerable, your doctor might recommend strong pain medication (narcotics) to help make you more comfortable.

Preparing for your appointment

If you have signs and symptoms of familial Mediterranean fever, you may begin by seeing your family doctor. You may be referred to a doctor who specializes in inflammatory diseases (rheumatologist).

Because appointments can be brief, and because there's often a lot of ground to cover, it's a good idea to arrive prepared. Here's some information to help you get ready for your appointment.

What you can do

• Write down your signs and symptoms, including how long you've been experiencing them.
• Collect your family history, as it might pertain to your condition. Note if you're of Mediterranean descent, for instance, or if you have a relative with familial Mediterranean fever.
• Take a list of all medications, as well as any vitamins or supplements you're taking.
• Write down questions to ask your doctor.

Some possible questions you might want to ask your doctor include:

• What do you think is causing my or my child's symptoms?
• What caused this condition?
• What treatments are available?
• What are the possible side effects of treatment?
• Are there any other possible treatments?
• Are there any restrictions on activity?
• Can I prevent this disorder in future children?

What to expect from your doctor
Your doctor is likely to ask you a number of questions, including:

• When did you first begin experiencing symptoms?
• Have your symptoms been continuous, or do they come and go?
• How long do your symptoms last?
• Can you think of anything that triggers your symptoms, or do you have warning signs that help you predict when they will occur?
• Is there anything you can do to stop or lessen the severity of your symptoms?
• Do your symptoms seem to follow a pattern?
• Do you have blood relatives with familial Mediterranean fever?

Tests and diagnosis

No specific test is available to detect familial Mediterranean fever. After ruling out other diseases, your doctor makes a diagnosis based on a combination of the following factors:

• Signs and symptoms. The most common signs and symptoms of familial Mediterranean fever are an unexplained, abrupt fever and severe pain in your abdomen, chest or joints. The abdominal pain may mimic appendicitis (inflammation of the appendix). These problems tend to improve spontaneously and then recur at a later time.
• Family history. A family history of familial Mediterranean fever increases your likelihood of developing the condition because the genetic mutation is passed from parents to their children.
• Ethnicity. Familial Mediterranean fever most often develops in people of Mediterranean origin, including Sephardic Jews, Armenians, Turks, North Africans, Arabs, and less frequently, Greeks and Italians. The condition has also been diagnosed in other ethnic groups, including Ashkenazi Jews, so FMF can't be diagnosed based on ethnicity alone.
• Blood tests. During an attack, blood tests may show elevated levels of certain markers that indicate an inflammatory condition in your body. An elevated level of white blood cells, which fight infections, is one such marker.
• Genetic testing. This test may determine if your genes have mutations that are associated with familial Mediterranean fever. Doctors don't commonly use genetic testing as a diagnostic tool because the available tests don't assess for all the gene mutations associated with the disorder. However, genetic testing may help confirm a diagnosis of FMF in people with atypical signs or symptoms.

Treatments and drugs

While there's no cure for familial Mediterranean fever, there is effective treatment. The most successful treatment for familial Mediterranean fever is a drug called colchicine. This medication is most effective when it's taken to prevent symptoms from occurring, instead of treating symptoms after they occur.

Colchicine is a drug, usually taken as a pill, which reduces inflammation in your body. Some people might need to take just one dose a day, while others might require smaller, more frequent doses to prevent attacks and to lessen side effects, such as diarrhea. People who can predict an impending attack because they feel discomfort or other predictable symptoms before an attack may be able to stop those attacks before they start by taking colchicine.

Reducing the frequency and intensity of symptoms
When you take colchicine on the schedule set by your doctor, the drug will likely reduce the frequency and intensity of your symptoms. It also lowers your risk of complications, especially amyloidosis. Colchicine can cause side effects such as muscle weakness or pain, tingling or numbness in your hands or feet, especially in older adults, in people with liver disease and in those whose kidneys aren't functioning properly. However, colchicine therapy is generally considered safe, even when taken long term. If your symptoms are not controlled by colchicine, then alpha-interferon, thalidomide, etanercept (Enbrel), infliximab (Remicade) or anakinra (Kineret) may be recommended. One study found that the antidepressant medications known as selective serotonin reuptake inhibitors (SSRIs) may be helpful in people who can't tolerate the side effects of colchicine.

Lifestyle and home remedies

These tips can help you manage familial Mediterranean fever:

• Take your medication on schedule. Sticking to your colchicine regimen is crucial for relieving your symptoms and preventing complications. Taking colchicine on a regular schedule may also reduce side effects of the medication.
• Discuss pregnancy with your doctor. If you'd like to start a family, talk to your doctor about how you can increase the chances that your baby will be healthy. Fortunately, colchicine therapy isn't associated with an increased risk of infertility or of abnormalities in a developing baby. If you become pregnant, you may find that the frequency and the severity of your symptoms lessen during pregnancy. It's not certain why symptoms may improve, but it may be related to hormonal changes.
• Fine-tune your diet. Some people with FMF notice that their attacks are lessened by following a low-fat diet. One side effect of colchicine therapy is lactose intolerance, so if you experience abdominal discomfort, such as bloating, a lactose-free diet may improve your symptoms.

Coping and support

Learning that you or your child has a chronic illness, such as familial Mediterranean fever, can be upsetting and frustrating. Here are some tips that may help you cope:

• Get educated. Learn enough about familial Mediterranean fever so that you know what to expect. Ask your doctor for brochures you can take with you, as well recommended websites to check out.
• Get support. Talking to a family member, trusted friend, or a counselor or therapist can allow you to vent your fears and frustrations. Some people also find support groups helpful because members truly understand what you're going through. Ask your doctor if there is a support group for people affected by familial Mediterranean fever in your area.