Let me tell you about my experiences with Familial Mediterranean Fever. Please note that I am not a doctor, and I can neither diagnose nor prescribe. I wanted to be a doctor but in those days girls were not encouraged to do so. I followed the traditional wisdom but continued my interest in all things scientific throughout my life. I consider myself to be a genealogist with a scientific bent. I CAN tell you about my journey to better health and how I handled this.

Just about 5 years ago I was diagnosed, with a variant of Familial Mediterranean Fever. My DNA tests for this disease came back negative for all KNOWN versions of this gene mutation. I was tested for 14 genes at that time. As I understand it there are now 72 mutations that can be tested for. I think I will likely not do any re-testing. The doctors believe that I have a variation of the gene, which has not yet been found and for hundreds of years the symptoms and the response to colchicine treatment have diagnosed FMF. I have improved so much with that treatment . Dr. Chris Morris of Kingsport, TN, the doctor who first recognized this pattern among Melungeon descendants says that a POSITIVE reaction to colchicine is a positive diagnosis of FMF for us. My own local doctor told me the same thing.

Familial Mediterranean Fever has many symptoms which do not quite fit together into a pattern that physicians can see, because in the United States it is thought to be very rare. I personally think it is not that rare. I can remember attacks of high fever and pain in my lower right side occurring as early as 8 years of age when my doctor said I had appendicitis. My mother details attacks from infancy. I would have a high fever and I would have hallucinations/nightmares during the attacks. The doctor told her he thought that I had had a mild case of polio at one point yet I had no polio after effects. I had these attacks periodically and in between I was a pretty normal child. Don't most children suffer with fevers of unknown origin from time to time?

As I grew older, the symptoms seemed to change, and I began to suffer with depression in Elementary school. Of course, it wasn't called that then, but I can recognize it now. The depression has continued all my life. In my 30s I began to experience worsening depression and the beginnin gsoffibromyalgia. By the time I was in my 40s, I was feeling a variety of symptoms, which were continuing to worsen and to remain with me for longer time periods in between periods of well being. I had had some physical accidents and some emotional traumas by that time and so my problems were blamed on that. By my late 40s, the well periods were few and far between. It got to the point that if I awakened and felt 'good' I thought something was wrong with me!

By this time, my doctors and many of my family thought that I was a hypochondriac because of the many and varied symptoms that I presented. I was told 'it is all in your head.' I was diagnosed previously and erroneously, it turns out, with fibromyalgia, (I had ALL the trigger points of fibro and my muscles ached so much at times that my mouth watered from the pain, like a popcorn hull between your teeth causes you to do. More on this symptom later.)

I was diagnosed by blood tests with rheumatoid arthritis. I had x-rays that showed osteo-arthritis. I suffered with chronic recurrent chemical depression, sleep apnea, sleep disorder with myoclonus, and Restless Leg Syndrome, colitis, spastic colon, gallbladder inflammation, appendicitis, possible kidney stones with their concurrent problems of vomiting and diarrhea, and so many other things that I can't even remember them. I had chronic respiratory problems, chest pains, sinus infections, allergies and asthma. I had thyroid problems that bounced up and down for years starting in my early teens.

FMF can affect the thyroid gland because this illness inflames the lining of all the body's organs. FMF also deposits a protein called amyloid and the thyroid can be involved in this. "Thyroid abnormalities were described in 19% of children with FMF and were more frequent among girls. A positive test for antithyroglobulin antibodies was found in several patients, but amyloid deposits were also found. Therefore careful examination for goiter, as well as measurement of serum thyroxine (T4), TSH, and antithyroid antibodies should be performed in all patients with FMF."
From:
http://home.coqui.net/myrna/peri1.htm

I had even looked into Chronic Fatigue Syndrome as a possible cause of my problems. All of these things didn't happen at once. As I said, as a child, I was pretty normal between attacks. Then I received the fibromyalgia diagnoses and lived with that for years, but the diagnoses kept being added and they grew worse as I grew older. Sound like I was a wreck? I was, but I am beginning to improve. It is like a miracle.

I came across the diagnosis of Familial Mediterranean Fever through my genealogical research. I think the number of descendants of these folks has been grossly under-estimated. Suffice it to say that I diagnosed myself, and took it to my doctor who had been treating me for 20 years. He laughed at me. I went to 2 other doctors where the same thing happened before finding the doctor where I was finally diagnosed. I explained that I was looking for a diagnosis of FMF and held up my hand, saying "Don't laugh, let me continue." I asked for the medicine colchicine as a trial. Dr. Henshaw said, "Oh, that is a very rare disease and I don't think you have that," I asked him if colchicine would cause me any harm if I took it for thirty days. He said, "NO." and I told him I wanted a trial prescription. He wrote me one. Two hours after I took the first dose, I knew it was going to work.

At the point when I took the medicine, I could not rise from a seated position without pushing or pulling myself up with my hands. My hands, arms, and shoulders in particular were in constant pain, both in the muscles and the joints. I could not hold a coffee cup or a glass of water without using two hands, no thumbs to hold them. My thumbs and wrists were red, swollen and painful to the touch. I could not raise my right arm above my head to comb my hair or put on clothes and getting it behind me to hook my bra was out of the question.

I moaned and groaned as I came down the steps in the morning, turned sideways and taking one step at a time while holding on to the rail with my finger tips from underneath the railing. My brain was foggy; I could not think clearly, nor concentrate for longer than a few minutes. I had trouble doing simple arithmetic in order to balance a checkbook. No anti-inflammatories even touched my pain and three tablets of 800mgs each of ibuprofen did not even dull it. Only high-octane narcotics, which knocked me out completely, worked and then when I awoke, I had to deal with the hangover they caused on top of everything else, so I stopped taking them and waited to die.

MY life was miserable. I was very unhappy and I hurt so much at times that I was sure I could not stand it. Stress seemed to make it more intolerable. I was forced to take early disability retirement from a position that I loved because I could no longer tell my employer that I would be there every day and from the beginning to the end of the day. I was 58 years old at this time. Remember that you may not have all these symptoms if you are younger, but you can. FMF works on the body's symptoms in a way that is best explained by the following:

In the course of day-to-day activities, people incur a lot of Micro-injuries; a muscle stretched a smidgen too far, bumping your hand on the table, and so on. Each time such an injury occurs, a substance called C5a is released. C5a is a chemotactic factor for neutrophils. A chemotactic factor is a substance that, basically, 'says', 'Come here and do this', to a cell.

Neutrophils are small white blood cells that are part of the normal non-specific immune system. They are the first cells to arrive at an injury, and have many, many functions, primarily as mediators of inflammation. They first cause the inflammation to occur; and then, when the need for inflammation is gone, they cause it to go away. They also act as scavengers, engulfing and digesting debris at the site of an injury.

They are pretty neat little cells; but, the important thing to remember is that, in the presence of C5a, they CAUSE inflammation; which, amongst other things, causes the release of more C5a. In 'normal' people, a protein called pyrin is made that INACTIVATES C5a. As long as pyrin is present, the neutrophils won't be called to the site of an injury. Now, for a micro-injury, in a healthy person, this is not a problem. The inflammatory response really isn't needed to control the site of the injury, and induce healing. In a larger injury, the amount of C5a produced overwhelms the pyrin, and the Neutrophils respond. This is a very neat feedback loop.

However in a person with FMF, the pyrin is either not present at all, or is present in less-effective forms or at lower levels. This is the reason that even very small injuries result in an inflammatory response by the neutrophils, which is inappropriate and which cause the release of more C5a, which calls more neutrophils . . . and so on. This response only stops when so many neutrophils are packed into the site of the injury that no more can get in.

This is CERTAINLY NOT a good thing. The reason that colchicine is an effective treatment for some people with FMF is that it reduces the speed and effectiveness of the neutrophil's response to C5a; thereby reducing the inflammatory response to injury. The downside of this treatment is that the neutrophils will also be sluggish in responding to a serious injury, which can compromise a person's whole immune system. I have found that my immune system had already been compromised. Before taking colchicine, it was take anti-biotics for two weeks, off of anti-biotics for two weeks and then on again. Since I started colchicine, I have had to take anti-biotics many less times than previously needed. I think this is an improvement. Understanding about FMF and its effect on my immune system allows me to better understand how to take care of myself and get the appropriate treatment.

Two researchers of FMF, Babior and Matzner (1997) suggested that the pathogenesis of FMF be as follows: Pyrin, or marenostrin, is postulated to activate the biosynthesis of a Chemotactic-factor inactivator, an enzyme that normally occurs in the serosal fluids. They suggested that a chemotactic factor (probably C5a; 113995) can be released by Sub clinical injury to the serosa during normal activities, but the amounts released are small enough that they are cleared by the inactivating enzyme before they can provoke an inflammatory reaction. In FMF the inactivating enzyme is absent, allowing the chemotactic factors to survive long enough to call in neutrophils, which then release a variety of products, including an enzyme that generates more C5a. The result is an upward spiral that culminates in a full-blown inflammatory reaction: an attack of FMF. Think of the cloud that comes with a nuclear explosion.

Picture the bottom of the column being encircled by C5a (the cause of pain) in an ever-widening spiral until it reaches the mushroom at the top of the cloud, which is the full blown FMF attack. If you have ever been told that you are overly sensitive to pain, here is the explanation. You are not overly sensitive. You have more pain because your body cannot relieve the pain the way those who are 'normal' can.

The medicine colchicine, which I started taking in 0.6mg daily doses, once daily and now take twice a day, and which the Merck Manual says can be taken in that amount 3 times a day, is made from a plant called the Autumn Crocus which grows in the Mediterranean. It is not harmful taken in small doses for a short time even if you do NOT have the disease. It needs to be carefully monitored by your doctor through periodic twice-yearly blood tests, and is available only by prescription. New information, just in, reveals that doctors in Israel find that there is relevance between familial Mediterranean fever and fibromyalgia pain.

The newest information on FMF and 'fibromyalgia' comes from Medscape Medline article that I found while searching on the Internet. You need to give your doctor the following information: To find the article, go to http://www.medscape.com. You must register and then click on MEDLINE. Type in Familial Mediterranean Fever connected to fibromyalgia. The first article to appear is the document you need to copy and take to your doctor along with the address above. The article concludes that 'the detection of FM (fibromyalgia) and definition of tenderness thresholds is relevant to this disease (FMF,) since musculoskeletal complaints are common in this group of patients but not always explained by objective findings.' With this article you can ask your doctor for a trial of the medicine because the connection is there for him to see.

Familial Mediterranean Fever, long mysterious, has now yielded up its secrets.
The cause is a lack of pyrin, a neutrophil protein, which slows down neutrophils when enough, have reached an area (Hosp. Pract. 33: 131, April 15, 1998.)
Lacking pyrin, neutrophils mob body cavities every once in a while. In addition to fever, patients may have pleuritis, arthritis, peritonitis, and/or a hot rash (looks like a strep infection) on the ankles.

Colchicine, famous for its ability to slow down neutrophils (as in acute gout), controls the attacks and prevents the dread complication of secondary amyloidosis.
As you can imagine, FMF can mimic most diseases. Don't miss it.
http://www.pathguy.com/lectures/spleen.htm#intro
Molecular genetic diagnosis: Ann. Int. Med. 129: 539, 1998.

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