Saturday, April 21, 2012
There is a LOT of information on Familial Mediterranean Fever on this blog. It begins with Nancy's PERSONAL EXPERIENCES with FMF and continues with descriptions of the disease, the symptoms of the disease, how it works and medical documentation from a variety of sources. I am not a doctor and I can not diagnose nor prescribe. I am a patient with FMF and a patient advocate. IF you need personal help you can reach me via e-mail at:
nmorri3924@aol.com
Here is my story with Familial Mediterranean Fever:
I think that by telling you my story with Familial Mediterranean Fever, it may help you see that this disease is easily mis-diagosed as everything under the sun. I am also including here an explanation of just HOW Familial Mediterranean Fever works:
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 10 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. At that time, I was tested for the 14 known genes As I understand it there are now over 170 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. This is called CLINICAL DIAGNOSIS.
I have improved so much with that treatment . Dr. Chris Morris of Kingsport, TN, the doctor who first recognized this pattern among Melungeon descendants (and I consider myself to be a Melungeon descendant, says that a POSITIVE reaction to colchicine is a positive diagnosis of FMF for us. My own local doctor told me the same thing. (Melungeons are a fascinating group of people who are found in the southeastern United States particularly in NC/VA/KY/TN/WV. They are believed to have a Mediterranean ancestry.)
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 beginnings of fibromyalgia. 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."
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. Without a word, I got up from his examing table and walked out of his office. I never returned.
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.
HOW FMF WORKS:
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.
Tuesday, September 20, 2011
A Melungeon connection to Familial Mediterranean Fever?
Some people never give up trying to defeat a proven fact. A person who writes a blog on the Melungeons (Melungeons are a group of folks in the U.S. who we believe have a Mediterranean ancestry.) has written about Familial Mediterranean Fever, about which she knows nothing. See a response to this blog written by the "OTHERS" on FMF here and on my blog:
A Melungeon connection to Familial Mediterranean Fever?
It never fails to amaze me that some people would rather see friends and relatives die, than admit that there might even be a SLIGHT possibility of an inherited illness amongst them. Familial Mediterranean Fever can be a FATAL illness left untreated. Why would anyone suggest that a relative die? What is so scary to some people that they would write about something that they have not researched, and which they deny is even connected to them?
Years ago, N. Brent Kennedy, author of The Melungeons: The Resurrection of a Proud People, told me that IF Familial Mediterranean Fever turned out to be an Appalachian thing rather than a Melungeon 'thing,' then the importance factor of this FACT was raised.
As both a patient with FMF and a patient advocate for others with this disease, I can state that it appears this is so. Cases of Familial Mediterranean Fever are being found all over the United States and in particular amongst those families having roots in the Appalachian Mountain ranges.
I moderate two Familial Mediterranean Fever sites, a mailing list on yahoogroups,
http://health.groups.yahoo.com/group/fmf_support/messages
(subscribe - fmf_support-subscribe@yahoogroups.com )
I also moderate a website that is connected to the United States "rarediseases" organization. The rare diseases group is connected to a world-wide group of researchers and patients who are attempting to find solutions and cures for this at present incurable illness. It is written in 5 languages:
http://www.rarediseasecommunities.org/en/community/familial-mediterranean-fever
Also see NORD, National Organization for Rare Diseases
http://www.rarediseases.org/
I have researched this illness and corresponded with doctors and other researchers. It is data from these sources that allows me to recommend doctors practicing in various states and countries to patients searching for an answer to serious, life-threatening health issues and to encourage them to ask their doctors to do the research that would allow them to TRY colchicine.
Years ago, my own doctors told me that a TRIAL of colchicine given in a specific amount and for a limited time would not hurt me even if I did not have the illness. A POSITIVE response to colchicine is a POSITIVE diagnosis of Familial Mediterranean Fever. And colchicine is the ONLY medication that prevents this illness from being fatal.
A recent blog noted that: "Some people have been misinformed that having Familial Mediterranean Fever proves a Melungeon connection."
Nothing could be farther from the truth! Having Familial Mediterranean Fever proves that somewhere in your ancestry you have Mediterranean ancestry. Many of us who have a Melungeon connection in our family lines, do believe that the Melungeons have a Mediterranean connection. After all, the Melungeons themselves noted that they were 'Portyghee.' Portugal is a Mediterranean country and probably one of the most ethnically mixed countries in the world.
When a person writes about a medical problem, that person needs to have not only compassion, but accurate information. The person writing the blog has neither.
The blog mentioned noted that: "The most dangerous aspect of this dislusional thinking is that the advice to just TRY colchicine is very dangerous advice because colchicine is a very dangerous drug." How disingenuous!
Since colchicine requires a prescription from a doctor, that is, a licensed MD, a suggestion to TRY colchicine must pass a rigorous medical procedure before any such prescription can be given.
The statement from this blog that: "An ethical Dr. would only prescribe colchicine if the benefits outweighed the danger. Leave the prescribing to a licensed physician." would be funny, IF it were not so dangerous to the health of those of us who have suffered through dozens of doctor visits to dozens of different doctors over dozens of years arriving at several dozen different misdiagnoses in order to arrive at the correct diagnosis and receive a script for the life-saving product called COLCHICINE. One does not say, 'Doc, give me colchicine and get it.'
As with most drugs there are side effects to colchicine. Given the fact that Familial Mediterranean Fever can be a FATAL illness, weighing the benefits, LIFE against DEATH, seems to me to swing the scales in the direction of life.
I would hope that patients would choose life. Listening to tripe such as that written on the other blog can lead to death.
Nancy
Familial Mediterranean Fever blog - 'my story' w/ FMF, and LOTS of medical documentation, charts etc.
http://familialmediterraneanfever.blogspot.com/
Familial Mediterranean Fever- rarediseasescommunityhttp://www.rarediseasecommunities.org/en/community/familial-mediterranean-fever
A Melungeon connection to Familial Mediterranean Fever?
It never fails to amaze me that some people would rather see friends and relatives die, than admit that there might even be a SLIGHT possibility of an inherited illness amongst them. Familial Mediterranean Fever can be a FATAL illness left untreated. Why would anyone suggest that a relative die? What is so scary to some people that they would write about something that they have not researched, and which they deny is even connected to them?
Years ago, N. Brent Kennedy, author of The Melungeons: The Resurrection of a Proud People, told me that IF Familial Mediterranean Fever turned out to be an Appalachian thing rather than a Melungeon 'thing,' then the importance factor of this FACT was raised.
As both a patient with FMF and a patient advocate for others with this disease, I can state that it appears this is so. Cases of Familial Mediterranean Fever are being found all over the United States and in particular amongst those families having roots in the Appalachian Mountain ranges.
I moderate two Familial Mediterranean Fever sites, a mailing list on yahoogroups,
http://health.groups.yahoo.com/group/fmf_support/messages
(subscribe - fmf_support-subscribe@yahoogroups.com )
I also moderate a website that is connected to the United States "rarediseases" organization. The rare diseases group is connected to a world-wide group of researchers and patients who are attempting to find solutions and cures for this at present incurable illness. It is written in 5 languages:
http://www.rarediseasecommunities.org/en/community/familial-mediterranean-fever
Also see NORD, National Organization for Rare Diseases
http://www.rarediseases.org/
I have researched this illness and corresponded with doctors and other researchers. It is data from these sources that allows me to recommend doctors practicing in various states and countries to patients searching for an answer to serious, life-threatening health issues and to encourage them to ask their doctors to do the research that would allow them to TRY colchicine.
Years ago, my own doctors told me that a TRIAL of colchicine given in a specific amount and for a limited time would not hurt me even if I did not have the illness. A POSITIVE response to colchicine is a POSITIVE diagnosis of Familial Mediterranean Fever. And colchicine is the ONLY medication that prevents this illness from being fatal.
A recent blog noted that: "Some people have been misinformed that having Familial Mediterranean Fever proves a Melungeon connection."
Nothing could be farther from the truth! Having Familial Mediterranean Fever proves that somewhere in your ancestry you have Mediterranean ancestry. Many of us who have a Melungeon connection in our family lines, do believe that the Melungeons have a Mediterranean connection. After all, the Melungeons themselves noted that they were 'Portyghee.' Portugal is a Mediterranean country and probably one of the most ethnically mixed countries in the world.
When a person writes about a medical problem, that person needs to have not only compassion, but accurate information. The person writing the blog has neither.
The blog mentioned noted that: "The most dangerous aspect of this dislusional thinking is that the advice to just TRY colchicine is very dangerous advice because colchicine is a very dangerous drug." How disingenuous!
Since colchicine requires a prescription from a doctor, that is, a licensed MD, a suggestion to TRY colchicine must pass a rigorous medical procedure before any such prescription can be given.
The statement from this blog that: "An ethical Dr. would only prescribe colchicine if the benefits outweighed the danger. Leave the prescribing to a licensed physician." would be funny, IF it were not so dangerous to the health of those of us who have suffered through dozens of doctor visits to dozens of different doctors over dozens of years arriving at several dozen different misdiagnoses in order to arrive at the correct diagnosis and receive a script for the life-saving product called COLCHICINE. One does not say, 'Doc, give me colchicine and get it.'
As with most drugs there are side effects to colchicine. Given the fact that Familial Mediterranean Fever can be a FATAL illness, weighing the benefits, LIFE against DEATH, seems to me to swing the scales in the direction of life.
I would hope that patients would choose life. Listening to tripe such as that written on the other blog can lead to death.
Nancy
Familial Mediterranean Fever blog - 'my story' w/ FMF, and LOTS of medical documentation, charts etc.
http://familialmediterraneanfever.blogspot.com/
Familial Mediterranean Fever- rarediseasescommunityhttp://www.rarediseasecommunities.org/en/community/familial-mediterranean-fever
Thursday, August 18, 2011
There is a LOT of information on Familial Mediterranean Fever on this blog. It begins with Nancy's PERSONAL EXPERIENCES with FMF and continues with descriptions of the disease, the symptoms of the disease, how it works and medical documentation from a variety of sources. I am not a doctor and I can not diagnose nor prescribe. I am a patient with FMF and a patient advocate. IF you need personal help you can reach me via e-mail at:
nmorri3924@aol.com
Here is my story with Familial Mediterranean Fever:
I think that by telling you my story with Familial Mediterranean Fever, it may help you see that this disease is easily mis-diagosed as everything under the sun. I am also including here an explanation of just HOW Familial Mediterranean Fever works:
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 10 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. At that time, I was tested for the 14 known genes As I understand it there are now over 170 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. This is called CLINICAL DIAGNOSIS.
I have improved so much with that treatment . Dr. Chris Morris of Kingsport, TN, the doctor who first recognized this pattern among Melungeon descendants (and I consider myself to be a Melungeon descendant, says that a POSITIVE reaction to colchicine is a positive diagnosis of FMF for us. My own local doctor told me the same thing. (Melungeons are a fascinating group of people who are found in the southeastern United States particularly in NC/VA/KY/TN/WV. They are believed to have a Mediterranean ancestry.)
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 beginnings of fibromyalgia. 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."
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. Without a word, I got up from his examing table and walked out of his office. I never returned.
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.
HOW FMF WORKS:
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.
nmorri3924@aol.com
Here is my story with Familial Mediterranean Fever:
I think that by telling you my story with Familial Mediterranean Fever, it may help you see that this disease is easily mis-diagosed as everything under the sun. I am also including here an explanation of just HOW Familial Mediterranean Fever works:
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 10 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. At that time, I was tested for the 14 known genes As I understand it there are now over 170 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. This is called CLINICAL DIAGNOSIS.
I have improved so much with that treatment . Dr. Chris Morris of Kingsport, TN, the doctor who first recognized this pattern among Melungeon descendants (and I consider myself to be a Melungeon descendant, says that a POSITIVE reaction to colchicine is a positive diagnosis of FMF for us. My own local doctor told me the same thing. (Melungeons are a fascinating group of people who are found in the southeastern United States particularly in NC/VA/KY/TN/WV. They are believed to have a Mediterranean ancestry.)
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 beginnings of fibromyalgia. 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."
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. Without a word, I got up from his examing table and walked out of his office. I never returned.
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.
HOW FMF WORKS:
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.
Sunday, May 8, 2011
Family Riddled with FMF needs DNA to find Middle Eastern Roots
The article noted below says that FMF can occur without Middle Eastern roots. That is not exactly true. FMF can occur when one does not know that they do indeed have Middle Eastern roots and only DNA can tell you if you do. Our genealogies will only go so far back and that may not indicate the Mediterranean ancestry that many of us have. I feel that articles like this one below can lead folks astray and we need to encourage more definitive studies of ancestry before making such a statement. See:
Familial Mediterranean fever can occur without Middle Eastern roots
Body and Mind staff
Posted: 05/04/2011 12:10 AM
"The diagnosis took them, their two equally afflicted siblings and the doctors who diagnosed and treat them by surprise. FMF is found primarily among people of Middle Eastern descent — Sephardic Jews, Arabs, Turks, Armenians — and sometimes Greeks and Italians. The background of Zelonis and DeVore is Northern and Western European.
“But familial Mediterranean fever can occur in any ethnic group,” Sachs said. "
http://mobile.pennlive.com/advpenn/db_96632/contentdetail.htm;jsessionid=10B342D08B6C9067B870F90BB1DC3213?contentguid=K0ir2b8A&detailindex=1&pn=0&ps=5&full=true
For more information on Familial Mediterranean Fever please see:
Familial Mediterranean Fever blog - 'my story' w/ FMF, and LOTS of medical documentation, charts etc.
http://familialmediterraneanfever.blogspot.com/
FMF Support mailing list:
fmf_support-subscribe@yahoogroups.com
Familial Mediterranean Fever Community
http://www.rarediseasecommunities.org/en/community/familial-mediterranean-fever
Familial Mediterranean fever can occur without Middle Eastern roots
Body and Mind staff
Posted: 05/04/2011 12:10 AM
"The diagnosis took them, their two equally afflicted siblings and the doctors who diagnosed and treat them by surprise. FMF is found primarily among people of Middle Eastern descent — Sephardic Jews, Arabs, Turks, Armenians — and sometimes Greeks and Italians. The background of Zelonis and DeVore is Northern and Western European.
“But familial Mediterranean fever can occur in any ethnic group,” Sachs said. "
http://mobile.pennlive.com/advpenn/db_96632/contentdetail.htm;jsessionid=10B342D08B6C9067B870F90BB1DC3213?contentguid=K0ir2b8A&detailindex=1&pn=0&ps=5&full=true
For more information on Familial Mediterranean Fever please see:
Familial Mediterranean Fever blog - 'my story' w/ FMF, and LOTS of medical documentation, charts etc.
http://familialmediterraneanfever.blogspot.com/
FMF Support mailing list:
fmf_support-subscribe@yahoogroups.com
Familial Mediterranean Fever Community
http://www.rarediseasecommunities.org/en/community/familial-mediterranean-fever
Wednesday, March 30, 2011
Article on colchicine price on gout patients as well as FMF patients:
What the following article fails to mention is the effect that having only one brand of colchicine has on patients who have Familial Mediterranean Fever. It seems that different brands do make a difference for different patients:
"A Giant Pain in the Wallet
How drug companies are making crucial, common drugs up to 100 times more expensive.
By Arthur AllenPosted Tuesday, March 29, 2011, at 7:09 AM ET
How did gout pills get so expensive?A drug called colchicine is all that keeps some 2 million American gout patients from suffering debilitating pain in their toes, elbows, wrists, and fingers. Doctors have prescribed the compound, derived from the seeds of the autumn crocus, for centuries. But patients who take colchicine woke up with a new symptom recently: a giant pain in the wallet."
http://www.slate.com/id/2289616/
Nancy
"A Giant Pain in the Wallet
How drug companies are making crucial, common drugs up to 100 times more expensive.
By Arthur AllenPosted Tuesday, March 29, 2011, at 7:09 AM ET
How did gout pills get so expensive?A drug called colchicine is all that keeps some 2 million American gout patients from suffering debilitating pain in their toes, elbows, wrists, and fingers. Doctors have prescribed the compound, derived from the seeds of the autumn crocus, for centuries. But patients who take colchicine woke up with a new symptom recently: a giant pain in the wallet."
http://www.slate.com/id/2289616/
Nancy
Monday, February 28, 2011
URLS for Familial Mediterranean Fever Research.
A Variety of URLS for Familial Mediterranean Fever Research.
The following articles cover a wide variety of symptoms and signs of FMF and include diagnosing the illness as well as treatment. Some are more technical than others and some may be good for printing and taking to your doctors if necessary:
Shariz Medical Journal - This article has the DIAGRAM of SYMPTOMS that I have often used.
http://semj.sums.ac.ir/vol7/apr2006/fmf.htm
Jewish Genetic Diseases - FMF
http://www.mazornet.com/genetics/familial_mediterranean_fever.htm
Mayo Clinic -
Familial Mediterranean fever
http://www.mayoclinic.com/health/familial-mediterranean-fever/DS00766
GENETICS Home Reference - FMF
http://ghr.nlm.nih.gov/condition/familial-mediterranean-fever
Molecular Genetics in Clinical Practice
Familial Mediterranean Fever: The
Genetics of Inflammation - this article has the map of spread of FMF throughout the Mediterranean, by Dr. Daniel Kastner, chief researcher FMF at NIH and pretty technical but worth taking a look at:
http://www.prontodiagnostics.com/pdfs/hospital%20fmf.pdf
Genetic and Rare Diseases Info - FMF
http://rarediseases.info.nih.gov/GARD/QnASelected.aspx?diseaseID=6421
National Human Genome Research Institute
http://www.genome.gov/12510679
University of MD,
http://www.umm.edu/ency/article/000363.htm
Merck Manual - FMF
http://www.merckmanuals.com/professional/sec19/ch297/ch297b.html
An interview w/ Dr. Terry Getzug - I posted to this site a couple of times.....
http://www.jewishjournal.com/jewish_diseases/item/familial_mediterranean_fever_an_interview_with_terri_getzug_md_20100725/
Uncommon clinical pattern of FMF: protracted febrile myalgia syndrome - this is the "fibromyalgia" of FMF - many in the USA are being given this diagnosis.
http://www.springerlink.com/content/g86037681x5l1q87/
TEXTBOOK of Medicine
http://www.brown.edu/Administration/Emergency_Medicine/emr/pages/fmf.html
MEFV (NM_000243.1) sequence variants
http://fmf.igh.cnrs.fr/ISSAID/infevers/search.php?n=1
INFEVERS Home page:
The registry of Hereditary Auto-inflammatory Disorders Mutations
(includes other fever disorders)
http://fmf.igh.cnrs.fr/ISSAID/infevers/
Love and health in family ties,
Nancy
The following articles cover a wide variety of symptoms and signs of FMF and include diagnosing the illness as well as treatment. Some are more technical than others and some may be good for printing and taking to your doctors if necessary:
Shariz Medical Journal - This article has the DIAGRAM of SYMPTOMS that I have often used.
http://semj.sums.ac.ir/vol7/apr2006/fmf.htm
Jewish Genetic Diseases - FMF
http://www.mazornet.com/genetics/familial_mediterranean_fever.htm
Mayo Clinic -
Familial Mediterranean fever
http://www.mayoclinic.com/health/familial-mediterranean-fever/DS00766
GENETICS Home Reference - FMF
http://ghr.nlm.nih.gov/condition/familial-mediterranean-fever
Molecular Genetics in Clinical Practice
Familial Mediterranean Fever: The
Genetics of Inflammation - this article has the map of spread of FMF throughout the Mediterranean, by Dr. Daniel Kastner, chief researcher FMF at NIH and pretty technical but worth taking a look at:
http://www.prontodiagnostics.com/pdfs/hospital%20fmf.pdf
Genetic and Rare Diseases Info - FMF
http://rarediseases.info.nih.gov/GARD/QnASelected.aspx?diseaseID=6421
National Human Genome Research Institute
http://www.genome.gov/12510679
University of MD,
http://www.umm.edu/ency/article/000363.htm
Merck Manual - FMF
http://www.merckmanuals.com/professional/sec19/ch297/ch297b.html
An interview w/ Dr. Terry Getzug - I posted to this site a couple of times.....
http://www.jewishjournal.com/jewish_diseases/item/familial_mediterranean_fever_an_interview_with_terri_getzug_md_20100725/
Uncommon clinical pattern of FMF: protracted febrile myalgia syndrome - this is the "fibromyalgia" of FMF - many in the USA are being given this diagnosis.
http://www.springerlink.com/content/g86037681x5l1q87/
TEXTBOOK of Medicine
http://www.brown.edu/Administration/Emergency_Medicine/emr/pages/fmf.html
MEFV (NM_000243.1) sequence variants
http://fmf.igh.cnrs.fr/ISSAID/infevers/search.php?n=1
INFEVERS Home page:
The registry of Hereditary Auto-inflammatory Disorders Mutations
(includes other fever disorders)
http://fmf.igh.cnrs.fr/ISSAID/infevers/
Love and health in family ties,
Nancy
Tuesday, April 13, 2010
Wall St. Journal article on Colcrys
•Wall Street Journal
•
•
•HEALTH INDUSTRY
•APRIL 12, 2010
An Old Gout Drug Gets New Life and a New Price, Riling Patients
•By JONATHAN D. ROCKOFF
A centuries-old drug used to treat excruciating gout pain had cost just pennies a tablet—until last year. Now, the retail price has skyrocketed to more than $5 and some of the manufacturers have ceased production amid a battle over marketing rights.
The tale of how this common gout drug, colchicine, became the costlier branded drug Colcrys offers a window into the Byzantine world of drug pricing. The price rise is a consequence of a Food and Drug Administration effort to improve the safety of long-used but unapproved drugs, with a trade-off often made between drug affordability and safety.
In July 2009, a Philadelphia drug maker received FDA approval to exclusively market colchicine for gout attacks for three years. The company, URL Pharma Inc., was taking advantage of a push to bring medicines predating the FDA, like colchicine, under the agency's regulatory umbrella. The FDA offers exclusive marketing rights if a drug maker conducts clinical trials.
URL Pharma had commissioned studies that confirmed its colchicine product's safety and efficacy, while demonstrating it should be taken at a lower dose than typical and not used with certain other medicines. The company is marketing its drug as Colcrys—and the retail cost averages $5 per pill, according to DestinationRx, a health-care data provider.
URL is also suing longtime manufacturers of unapproved colchicine, saying the companies are now illegally marketing their products. Some of the companies are fighting the lawsuits. Some themselves have raised prices—including one increase of just under a dollar per tablet to $1.17, according to DestinationRx. The higher price for Colcrys was first reported by Kaiser Health News.
There were 3.5 million prescriptions and $6.4 million in sales in 2008, according to the most recent data available from IMS Health, a drug-data firm.
"It's not a new product. It's been out for hundreds of years. To all of a sudden have to pay $125 or $150 a month, after it only cost $5 or $10 a month, is a real problem," said Stanley Cohen, a Dallas doctor who is the president of the American College of Rheumatology. He met with the FDA to express concern about the price increase.
The chief executive of URL Pharma, Richard Roberts, said that it priced Colcrys in line with other approved, branded drugs used to treat gout pain. To help patients afford Colcrys, Dr. Roberts said, the company is offering to pay a portion of co-pays, and it is providing a three-months' supply to low-income patients for $15.
Eileen Wood, vice president of pharmacy and health-quality programs at CDPHP, an insurer in New York state, said insurers will have to absorb much of the added expense. URL's contribution was "not any new therapeutic tool, not new science; they just added cost," she said.
Nancy Sparks Morrison, a retired schoolteacher who suffers from familial Mediterranean fever, an inflammatory disorder that's treated with colchicine, said she is buying colchicine from Canada because she can't afford Colcrys. Ms. Morrison said she plans to get help from URL Pharma to pay for Colcrys because the company has just expanded its assistance program. "I'm retired on Social Security, and I have a small pension," said Ms. Morrison, 71 years old, who lives outside Charleston, W.Va.
The price increase is an unintended consequence of the FDA's nearly four-year-old initiative to regulate unapproved drugs. These medicines were sold before the FDA was established, and therefore weren't required to undergo approval. After decades of use, the medicines are considered safe by doctors, but haven't been proven to satisfy the agency's standards. Colchicine's use has been traced back to the sixth century, according to the FDA.
Seventy drugs that were grandfathered have been approved since the FDA began its initiative, most notably pain reliever Vicodin, from Amneal Pharmaceuticals LLC, the FDA said.
The FDA had hoped a significant price increase wouldn't follow Colcrys's approval and regrets the increase, said Janet Woodcock, director of the agency's Center for Drug Evaluation and Research. Dr. Woodcock encouraged more competition, saying another company could seek approval for colchicine's regular use in gout, rather than the acute use that URL Pharma received approval for.
There had been no standard for dosage before FDA approval. Colchicine's excessive use can cause side-effects, such as severe diarrhea that is potentially fatal. The FDA said it receives reports of five deaths a year, on average, involving patients who took colchicine tablets.
"We took bad guidance, even guesswork, and made this evidence-based medicine," Dr. Roberts said.
Closely held URL Pharma, which is owned by a hedge fund, a private investor and employees, is a longtime seller of generic drugs, including colchicine. When the FDA launched its push, the company began searching for those with safety risks whose patients could benefit from clinical testing, Dr. Roberts said.
URL Pharma said its 17 clinical trials of colchicine involved a total of 988 patients. The trials showed that gout patients need take two tablets after an attack and one more an hour later, the FDA said. Trials also demonstrated side-effects from use with certain other medicines, including some antibiotics and antihypertensive medicines. Those are now flagged on the label of Colcrys.
After obtaining FDA approval of Colcrys, URL Pharma went to federal court to sue manufacturers of colchicine, including Excellium Pharmaceutical Inc., Vision Pharma LLC, Watson Pharmaceuticals Inc. and West-Ward Pharmaceutical Corp., saying they have been illegally marketing their colchicine products since Colcrys's approval. A fifth company, Qualitest Pharmaceuticals, settled and stopped production. The four companies are fighting the lawsuits.
"You have this product out for at least a hundred years and all of a sudden it's no good?" said Lou Dretchen, who oversees sales and marketing at Excellium of Fairfield, N.J. Mr. Dretchen said the small, closely held generic drug maker stopped colchicine production after URL Pharma sued. The other companies declined to comment.
Mon Apr 12, 2010 1:43 pm
--------------------------------------------------------------------------------
•
•
•HEALTH INDUSTRY
•APRIL 12, 2010
An Old Gout Drug Gets New Life and a New Price, Riling Patients
•By JONATHAN D. ROCKOFF
A centuries-old drug used to treat excruciating gout pain had cost just pennies a tablet—until last year. Now, the retail price has skyrocketed to more than $5 and some of the manufacturers have ceased production amid a battle over marketing rights.
The tale of how this common gout drug, colchicine, became the costlier branded drug Colcrys offers a window into the Byzantine world of drug pricing. The price rise is a consequence of a Food and Drug Administration effort to improve the safety of long-used but unapproved drugs, with a trade-off often made between drug affordability and safety.
In July 2009, a Philadelphia drug maker received FDA approval to exclusively market colchicine for gout attacks for three years. The company, URL Pharma Inc., was taking advantage of a push to bring medicines predating the FDA, like colchicine, under the agency's regulatory umbrella. The FDA offers exclusive marketing rights if a drug maker conducts clinical trials.
URL Pharma had commissioned studies that confirmed its colchicine product's safety and efficacy, while demonstrating it should be taken at a lower dose than typical and not used with certain other medicines. The company is marketing its drug as Colcrys—and the retail cost averages $5 per pill, according to DestinationRx, a health-care data provider.
URL is also suing longtime manufacturers of unapproved colchicine, saying the companies are now illegally marketing their products. Some of the companies are fighting the lawsuits. Some themselves have raised prices—including one increase of just under a dollar per tablet to $1.17, according to DestinationRx. The higher price for Colcrys was first reported by Kaiser Health News.
There were 3.5 million prescriptions and $6.4 million in sales in 2008, according to the most recent data available from IMS Health, a drug-data firm.
"It's not a new product. It's been out for hundreds of years. To all of a sudden have to pay $125 or $150 a month, after it only cost $5 or $10 a month, is a real problem," said Stanley Cohen, a Dallas doctor who is the president of the American College of Rheumatology. He met with the FDA to express concern about the price increase.
The chief executive of URL Pharma, Richard Roberts, said that it priced Colcrys in line with other approved, branded drugs used to treat gout pain. To help patients afford Colcrys, Dr. Roberts said, the company is offering to pay a portion of co-pays, and it is providing a three-months' supply to low-income patients for $15.
Eileen Wood, vice president of pharmacy and health-quality programs at CDPHP, an insurer in New York state, said insurers will have to absorb much of the added expense. URL's contribution was "not any new therapeutic tool, not new science; they just added cost," she said.
Nancy Sparks Morrison, a retired schoolteacher who suffers from familial Mediterranean fever, an inflammatory disorder that's treated with colchicine, said she is buying colchicine from Canada because she can't afford Colcrys. Ms. Morrison said she plans to get help from URL Pharma to pay for Colcrys because the company has just expanded its assistance program. "I'm retired on Social Security, and I have a small pension," said Ms. Morrison, 71 years old, who lives outside Charleston, W.Va.
The price increase is an unintended consequence of the FDA's nearly four-year-old initiative to regulate unapproved drugs. These medicines were sold before the FDA was established, and therefore weren't required to undergo approval. After decades of use, the medicines are considered safe by doctors, but haven't been proven to satisfy the agency's standards. Colchicine's use has been traced back to the sixth century, according to the FDA.
Seventy drugs that were grandfathered have been approved since the FDA began its initiative, most notably pain reliever Vicodin, from Amneal Pharmaceuticals LLC, the FDA said.
The FDA had hoped a significant price increase wouldn't follow Colcrys's approval and regrets the increase, said Janet Woodcock, director of the agency's Center for Drug Evaluation and Research. Dr. Woodcock encouraged more competition, saying another company could seek approval for colchicine's regular use in gout, rather than the acute use that URL Pharma received approval for.
There had been no standard for dosage before FDA approval. Colchicine's excessive use can cause side-effects, such as severe diarrhea that is potentially fatal. The FDA said it receives reports of five deaths a year, on average, involving patients who took colchicine tablets.
"We took bad guidance, even guesswork, and made this evidence-based medicine," Dr. Roberts said.
Closely held URL Pharma, which is owned by a hedge fund, a private investor and employees, is a longtime seller of generic drugs, including colchicine. When the FDA launched its push, the company began searching for those with safety risks whose patients could benefit from clinical testing, Dr. Roberts said.
URL Pharma said its 17 clinical trials of colchicine involved a total of 988 patients. The trials showed that gout patients need take two tablets after an attack and one more an hour later, the FDA said. Trials also demonstrated side-effects from use with certain other medicines, including some antibiotics and antihypertensive medicines. Those are now flagged on the label of Colcrys.
After obtaining FDA approval of Colcrys, URL Pharma went to federal court to sue manufacturers of colchicine, including Excellium Pharmaceutical Inc., Vision Pharma LLC, Watson Pharmaceuticals Inc. and West-Ward Pharmaceutical Corp., saying they have been illegally marketing their colchicine products since Colcrys's approval. A fifth company, Qualitest Pharmaceuticals, settled and stopped production. The four companies are fighting the lawsuits.
"You have this product out for at least a hundred years and all of a sudden it's no good?" said Lou Dretchen, who oversees sales and marketing at Excellium of Fairfield, N.J. Mr. Dretchen said the small, closely held generic drug maker stopped colchicine production after URL Pharma sued. The other companies declined to comment.
Mon Apr 12, 2010 1:43 pm
--------------------------------------------------------------------------------
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