Familial Mediterranean fever

Familial Mediterranean fever (FMF) is a genetic autoinflammatory disorder that causes recurrent fevers and painful inflammation of your abdomen, chest and joints.

FMF is an inherited disorder that usually occurs in people of Mediterranean origin — including those of Jewish, Arab, Armenian, Turkish, North African, Greek or Italian ancestry. But it can affect people in any ethnic group.

FMF is typically diagnosed during childhood. While there's no cure for this disorder, you may be able to relieve or even prevent signs and symptoms of FMF by following your treatment plan.

Signs and symptoms of familial Mediterranean fever usually begin during childhood. They occur in bouts called attacks that last 1-3 days. Arthritic attacks may last for weeks or months.

Signs and symptoms of FMF attacks vary, but can include:

• Fever
• Abdominal pain
• Chest pain, which can make it hard to breathe deeply
• Painful, swollen joints, usually in the knees, ankles and hips
• A red rash on your legs, especially below your knees
• Muscle aches
• A swollen, tender scrotum

The attacks generally resolve spontaneously after a few days. Between attacks, you'll likely feel back to your typical health. Symptom-free periods may be as short as a few days or as long as several years.

In some people, the first sign of FMF is amyloidosis. With amyloidosis, the protein amyloid A, which is not typically found in the body, builds up in organs — especially the kidneys — causing inflammation and interfering with their function.

See your health care provider if you or your child has a sudden fever accompanied by pain in the abdomen, chest and joints.

Familial Mediterranean fever is caused by a gene change (mutation) that's passed from parents to children. The gene change affects the function of an immune system protein called pyrin, causing problems in regulating inflammation in the body.

In people with FMF, change occurs in a gene called MEFV. Many different changes in MEFV are linked to FMF. Some changes may cause very severe cases, while others may result in milder signs and symptoms.

It's unclear what exactly triggers attacks, but they may occur with emotional stress, menstruation, exposure to cold, and physical stress such as illness or injury.

Factors that may increase the risk of familial Mediterranean fever include:

• Family history of the disorder. If you have a family history of FMF, you have a higher risk of the disorder.
• Mediterranean ancestry. If your family can trace its history to the Mediterranean region, your risk of the disorder may be increased. FMF can affect people in any ethnic group, but it may be more likely in people of Jewish, Arab, Armenian, Turkish, North African, Greek or Italian descent.

Complications can occur if familial Mediterranean fever isn't treated. Inflammation can lead to complications such as:

• Amyloidosis. During attacks of FMF, your body may produce a protein called amyloid A, not typically found in the body. Buildup of this protein causes inflammation, which can cause organ damage.
• Kidney damage. Amyloidosis can damage the kidneys, causing nephrotic syndrome. Nephrotic syndrome occurs when your kidneys' filtering systems (glomeruli) are damaged. People with nephrotic syndrome 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.
• Joint pain. Arthritis is common in people with FMF. The most commonly affected joints are the knees, ankles and hips.
• Infertility. Untreated inflammation caused by FMF may affect the reproductive organs, causing infertility.
• Other complications. These can include inflammation in the heart, lungs, spleen, brain and superficial veins.

Tests and procedures used to diagnose familial Mediterranean fever include:

• Physical exam. Your health care provider may ask you about your signs and symptoms and do a physical exam to gather more information.
• Review of your family medical history. A family history of FMF increases your likelihood of developing the condition because this genetic change is passed from parents to their children.
• Lab tests. During an attack, blood and urine 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. Protein in the urine that may indicate amyloidosis is another.
• Genetic testing. Genetic testing may determine if your MEFV gene contains a gene change that is associated with FMF. Genetic tests aren't advanced enough to test for every gene change that's linked to FMF, so there is a possibility of false-negative results. For this reason, health care providers typically don't use genetic tests as the sole method of diagnosing FMF.

Genetic testing for FMF may be recommended for your first-degree relatives, such as parents, siblings or children, or for other relatives who may be at risk. Genetic counseling can help you understand gene changes and their effects.

There's no cure for familial Mediterranean fever. However, treatment can help relieve symptoms, prevent attacks and prevent complications caused by inflammation.

Medications used to relieve symptoms and prevent attacks of FMF include:

• Colchicine. Colchicine (Colcrys), taken in pill form, reduces inflammation in your body and helps prevent attacks and the development of amyloidosis. Work with your doctor to determine the best dosing strategy for you. Some people take one dose a day, while others need smaller, more-frequent doses. Common side effects include abdominal pain, nausea and diarrhea. Treatment is generally lifelong.
• Other drugs to prevent inflammation. For people whose signs and symptoms aren't controlled with colchicine, medications that block a protein called interleukin-1, which is involved in inflammation, may be prescribed. Canakinumab (Ilaris) is approved by the U.S. Food and Drug Administration (FDA) for FMF. Although not FDA-approved specifically for FMF, other options include rilonacept (Arcalyst) and anakinra (Kineret).

Colchicine is effective in preventing attacks for most people. To lessen the severity of symptoms during an attack, your health care provider may recommend intravenous fluids and medications to reduce fever and inflammation and control pain.

Regular appointments with your health care provider are important to monitor your medications and your health.

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:

• Learn about FMF. Find out enough about FMF so that you feel comfortable making decisions about your or your child's care. Ask your health care provider for good sources of information to get you started.
• Find someone to talk with. Talking to a family member, trusted friend, or a counselor or therapist can allow you to express your fears and frustrations. Some people also find support groups helpful because members truly understand what you're going through. Ask your health care provider if there is a support group for people who have FMF in your area.

If you have signs and symptoms of familial Mediterranean fever, you may begin by seeing your family health care provider. Your health care provider may refer you to a specialist in inflammatory diseases (rheumatologist).

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

What you can do

• Be aware of any pre-appointment restrictions. At the time you make the appointment, be sure to ask if there's anything you need to do in advance, such as restrict your diet to prepare for testing.
• Make a list of any symptoms you're experiencing, including any that may seem unrelated to the reason for the appointment.
• Make a list of key personal information, including any major stresses or recent life changes.
• Make a list of all medications, vitamins or supplements that you're taking, and the doses.
• Consider taking a family member or friend along. Sometimes it can be difficult to remember all the information provided during an appointment. Someone who accompanies you may remember something that you missed or forgot.
• Make a list of questions to ask your health care provider.

Your time with your health care provider is limited, so preparing a list of questions can help you make the most of your time together. List your questions from most important to least important in case time runs out. Questions you might want to ask 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?
• If other health problems are present, how can they be treated as well?
• Are there any restrictions on activity?
• Should my family members be tested?
• If I want to have more children, can I protect them from this disorder?

What to expect from your doctor

Your health care provider 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?
• What seems to trigger your symptoms, and what warning signs help you predict when they will occur?
• Is there anything you 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?