IVN & Fibromyalgia
By Doctor Erich Ryll DISCUSSED BY: ERICH D. RYLL, M.D.
Assistant Clinical Professor of Medicine
Division of infectious & Immunologic Diseases
Department of International Medicine
University of California
In the spring and summer of 1975, there was a major, severe epidemic of a communical, apparent viral disease at the Mercy San Juan Hospital in Carmicheal, a suburb of Sacramento, California. It occurred in February, and the bulk of the disease happened between July and November of 1975. Cases continued to occur, although few, until 1978
The epidemic involved all departments of the hospital. It was equally severe in all departments.
I was appointed chairmen of a committee to investigate the outbreak. At the time, I feared that there might be fatalities and so Asked that the CDC (Communicable Disease Center, Atlanta, Georgia) become involved. An epidemiologist fro there spent a week at the hospital. Another epidemiologist from the State came for the day.
Cultures were obtained for all known viruses, bacteria, and rickettsiae, and all were negative. The disease was apparently due to a new agent of disease.
At the time, we did a literature search and found three reports of outbreaks that were called EPIDERMIC PHLEBODYNIA (meaning painful veins). While the disease at Mercy San Juan was somewhat similar, it included many more features that were subscribed in epidermic phlebodynia and so at the time, I believed it was not the same disease. Later , additional literature search showed that the disease was very similar to epidermic neuromyasthenia/ myalgic encephalomyelitis. But toublingly, very few if any, vascular features were mentioned.
Since the very beginning, I have followed these patients on a virtual daily basis-in 1992, now for 17 years. This continuos observation and study is perhaps the longest interval that anyone has ever studied such an disease. I have, throughout the years, learned all the nuances of the disease. Because the symptoms are so many and often seemingly bizarre, I often attempted to disclaim them as being real. But I learned that the patience were always right and that I had to have an open mind. This disease is humbling.
One must remember what a famous French physician said a year ago, Jean Martin Charcot:
"DISEASE IS VERY OLD AND NOTHING ABOUT IT HAS CHANGED. IT IS WE WHO CHANGE AS WE LEARN TO RECOGNIZE WHAT FORMERLY HAS BEEN IMPERCEPTIBLE."
Infectious venulitis (IVN) is a disease caused by an as yet unidentified virus. This disease begins by an in fluenza-like onset with headaches, sore throat, fever, dizziness, runny nose, congested head, nausea, vomiting, muscle aching, extremity pain, and other features. Unlike ordinary flu, however, this initial phase of IVN can last as long as a year and longer without let up. During this initial flu state, that I call a flu-storm because it lasts so long in many patients, sufferers are very drowsy at times - almost in a light coma. The extremity discomfort is often described as a burning, searing sensation. Joint pains can be sever cases, patients have frequent bruises for unexplained reasons and swollen, painful veins.
After the initial flu state leaves, the patients are still not well. They have a constant plateau of illness punctuated by unpredictable relapses. In a menstruating woman, relapses are apt to occur during menses or during menses, the disease is worse with increased pain and disability. During relapses they may have resumption of the many flu-like symptoms including drowsiness, headaches, fever and other features. Some patients have a relatively mild flu onset, only to have years later a relapse that is much more severe than the initial illness.
The disease is frightening to patients because of the severity and many features. Physicians are not trained to diagnose an illness that encompasses so many signs and symptoms. Two common statements by patients during the initial illness are: "I HURT ALL OVER" and "I AM GOING TO DIE".
Patients suffering from IVN have the following features:
SEVERE EXHAUSTION AND WEAKNESS
The exhaustion that occurs in this disease is profound and unusual. Patients often are not even able to hold up their heads. They have a compelling need to sleep. During relapses, patients have been known to sleep around the clock for days on end. The usual sleep pattern requires many more hours than usual. The sleep pattern is disturbed and is not restful. And yet, during waking hours, patients feel sleepy much of the time. A common statement is: "I LIVE IN A FOG" . Strength is greatest for most early in the morning. After a short time, endurance fades and patients find that performing the slightest tasks requiring little effort formerly, now can not be done. Some patients find that they can do small tasks in spurts, resting between times. During relapses, many patients can be totally helpless and unable to even care for themselves. Walking at all can become impossible and patients have been known to crawl to the bathroom on hands and knees.
Most women love to shop, but for a woman with IVN, it may be next to impossible to do. I have suggested that they obtain wheelchairs for activities such as shopping and other social events. They can then tolerate more extended activity. Many patients find that they can think more clearly when lying down and are able to do a limited amount of work while in the prone position. One patient who was desperately trying to hang onto her job would dash down to her car on her breaks in order to rest and restore her energy in an effort to keep on working. Patients have been known to fall asleep inappropriately, at times in mid conversation One severely ill patient reported that at time her head would drop onto her chest while she was standing and she would be asleep.
DISTURBANCE OF COGNITION/MENTATION
Short term memory can be severely impaired. Patients cannot remember where they place items or store them in inappropriate sites, such as putting a book in the refrigerator, etc. Calculating numbers is difficult. In the severely ill, checkbook cannot be balanced or even the most simple arithmetic accomplished. They cannot take care of their own financial affairs. Filling out forms can be impossible. Mental work of any kind becomes difficult or impossible. Patients cannot put their mind to words - it is as though the brain is no longer connected to the tongue. Concentration can be severely impaired. Directions are difficult to follow. Women often cannot follow cookbook recipes. Reading is difficult. Patients must read again and again to comprehend meaning and to retain.
Over confusion is common. Many have great difficulty in driving and often get lost in familiar neighborhoods. Street signs are difficult to follow and patients cannot decides at times which way to turn. Some have gotten lost on their way to my office, finding themselves in a different part of town. They had to call spouses or family members to get them. Cars cannot be found in parking lots. Others often report that when driving they suddenly realize that they don't know where they are going and others have stated that upon arrival at a destination, they did not know how to find their way home. There are frequent mental lapses.
Because of a frightening new disease that physicians cannot recognize, diagnose or understand and because it seems never to go away, patients become depressed. Upon visiting physicians, this depressions recognized and blamed for the entire illness. This of course is not true. Further, the viral disease itself is also in the brain and there may be an element of organic depression due to the virus.
Panic is common and can be severe. Rarely, patients can become psychotic and have hallucinations. But patients realize usually that these occur. They know that their minds are not working properly unlike in Alzheimer's syndrome when patients do not seem to have an awareness of their true state.
NERVOUS SYSTEM ABNORMALITIES
Patients are usually dizzy on an intermittent basis. Rarely, some are dizzy all the time. They are incoordinate and lurch about. Attempting to go through a doorway, they will hit the door jamb instead. They can have difficulty in performing fine movements such as writing. They have difficulty in judging distances - lack of spatial perception. Some are totally unable to drive; most others learn that there are days when they cannot safely drive an automobile.
Falls are common. Patients often relate that their legs simply give way and they fall. Others state that severe dizziness has caused them to fall. Many do not know what happens. Patients have injured themselves severely at times by falling. Fainting episodes are not unusual; patients usually do not have insight into the reasons. Patients have occasionally experienced sudden fainting while driving and awakened to find themselves in ditches, etc. Epileptic like seizures are seen rarely. Small strokes are not unusual. Many patients have definite weakness, sometimes of a given extremity, other times in general. There have been no major strokes to date, although some patients have persistent weakness of extremities after small strokes. Some have had to use canes, walkers, wheelchairs and been bed confined.
Patients usually drop items unexpectedly from their hands. Women often burn themselves inadvertently in the kitchen. Blurred vision is common and ringing of the ears as well. Some patients experience such a roaring or fluttering sound in their ears that it is most difficult to tolerate. Numbness and tingling of extremities is common.
The autonomic nervous system is usually deranged in this disease the portion that controls sweating, blushing and so on. Patients thus have episodes of flushing and sweating. Hands are often hot and wet with sweat; often they are bright red or mottled. At times hands and feet can be cold and very clammy. Some have been known to have deep purple and extremely cold hands. When patients are in relapse, others can immediately notice that they are not well as they are often pale. Family members and close associates are usually able to tell when a patient is feeling worse than usual by their appearance.
Pain can be very severe in this disease. Muscles are painful and tire easily. Joint exhibit a peculiar type of arthritis. The areas around the joints becomes inflamed. At times, although this is much more unusual, there can be swelling of joints. While joints are uncomfortable, they are not destroyed by this disease. The arthritis in this disease is migratory - it seems to travel around. Patients at times relate that they feel as though a hot poker is being pushed through their veins, notably those of the legs. They sting and burn. A majority of patients have ulcer like symptoms and some, more rarely, have ulcers. In addition properly and that the gastrointestinal tract is sluggish.
Of all the areas of pain, headache is often the worst. It is often accompanied by nausea, dizziness and vomiting. Light bothers their eyes most of the time, worse at the time of headache. At their most severe, headaches are worse than migraine and difficult to control with medications.
Pain and all symptoms of this disease are made worse by exercise. A patient during a better period might try to exercise normally and the find he or she must spend days in bed as a result to recuperate. A common statement is "I PAY FOR EVERYTHING THAT I DO".
The discomfort of these patients is made much worse by the hostility that they encounter from family, friends and many physicians. Spouses have been known to be disbelieving and totally unsupportive. This has led to severe martial stress or dissolution. Children become burned out and friends do not always want to hear that a patient doesn't feel well. As a result, many patients finally remain quiet. Panic and depression occur when the patient realizes he is not improving. Because he or she has been told so often that nothing is physically wrong with them, they begin to believe that they are "crazy"
At the onset of their disease, many patients have unexplained bruises (without any trauma) . These often sting and burn. More severe cases can exhibit swollen veins, painful in nature. At times, clots have formed in veins, but usually not in the deep circulation. Small veins can suddenly break, with a stinging sensation leaving a bruise. Veins can be inflamed even when they are not visible on the surface.
A RELAPSING COURSE
Except for the mildest cases - those who have symptoms only during a relapse - patients have a constant plateau of illness during which they are never entirely well. One cannot during these times gauge their illness because appearances can be deceiving. Bear in mind that many patients with cancer, heart disease, diabetes and other severe illnesses often appear to be normal to the casual observer as one encounters them at the grocery store, church and other places. During relapses anyone can tell that a patient is not well.
Relapses can be induced by physical, emotional or environmental stress. Again, in the menstruating woman, the disease is worse at this time and a relapse is apt to occur at this time. Relapses can last for indefinite periods from weeks to months.
To this date, there is no conclusive test or tests that can tell one with certainty that they have this disease. There are many, however that can be abnormal, many of them involving the immune system.
An elecrtomyogram is frequently abnormal, showing damage to nerves. A magnetic resonance brain image often reveals evidence of demyelination. We find this in multiple sclerosis, as well and probably in other virus diseases. (Multiple sclerosis is not known at this time to be caused by virus.) A specialized SPECT scan shows evidence of impaired brain circulation in nearly all of the patients, confirming the vascular nature of this disease. Tests for muscle often show abnormalities and damage, although muscles do not visibly shrink.
There is currently no treatment that cures the disease. Gamma globulin is useful in a majority of patients to improve function. A new drug called Ampligen is being studied and may be available within a year. These two treatment, however, are expensive and insurance carriers are loathe to pay for them.
Beyond this, there are many things that can be done to improved better function. One must always remain positive it aids the immune system in holding the disease in check. You must restructure your life. Accept that you have this disease and live with it's limitation. Be as normal as you can but do less of everything, rest is essential and restorative. Gentle exercises are advised so as to maintain muscle tone.
The general tendency is to slowly improve and the majority of you will recover much of your function. Many of you will recover virtually completely and will be able to live entirely normal lives. Mild cases recover quickly and in all probability are not diagnosed. (They do not even fit the diagnostic criteria for the disease). A smaller percentage will remain ill.
I failed to mention one last entity that is currently very popular and about which you may have heard something. It is fibromyalgia or fibrositis or fibromyositis.
What is fibromyalgia? It is an inflammation of joints and musculoligamentous connections - where muscles attach to joints and bones.
Early on, investigators in this field said that in fibromyalgia, if one exercise one feels much better - now they do not say this. It is a term used by rheumatologists chiefly, although others now are using it too. They used to say it was a disease of women who are anxious and depressed - now they say this less and less.
If you were to see a rheumatologist, many specialists in internal medicine and others these days, you would be labeled as having fibromyalgia . Researchers in this area - at least some of them - now may also say that it comes from a viral disease.
Now I have known for 17 years that you have a form of fibromaygia - it is due to IVN. But you have much more - It is just one facet of your disease. Fibromyalgia can occur with many conditions. To mention a few: systemic lupus, erythematosis, collagen vascular diseases of all kinds, rheumatoid arthritis, Lyme disease and many others. I have found in examining people that other viral diseases can cause this - but it does not persist as it does in IVN. Furthermore, in Fibromalgia, vascular features are not mentioned and the crucial features of my physical diagnosis are not mentioned and the crucial features of my physical diagnosis are not included. I am afraid that investigators working in this area are including fibromyalgia due to many causes, including that due to IVN. This further beclouds the issue and confuses those working in this area.
IVN may be the same or closely related to a disease that is in the United Kingdom called MYALGIC ENCEPHALOMYELITIS and in this country, EPIDEMIC NEUROMYASTHENIA. These two are the same disease and were first described in an epidemic that took place in Los Angeles. This epidemic was reported by the National Institute of Health in the form of a very thick public health report. Since then, ME and ENM have been reported worldwide, usually in closed, contained populations such as monasteries, convents, schools, military barracks and especially hospitals. IVN is identical to ME/ENM with the exception of the vascular features. There were several references to vascular involvement but it was not striking. Vascular features were perhaps more prominent in the epidemic at the Mercy San Juan Hospital in 1975, or they were simply not recognized in other outbreaks around the world. In 1955, two researchers studying an epidemic of ME performed studies on monkeys, some of whom died. Definite vascular features were reported by them.
In 1984 I visited New Zealand and found many people there suffering from a milder form of IVN (called ME by them). I spoke to large groups of people and appeared on National Radio and TV. I examined patients with Dr. Murdoch, a leading researcher there and showed him my method of examination that he has since used.
Also in 1984, I presented a paper at the Interscience Conference for Antibiotics and Chemotherapy, and arm of the American Society for Microbiology, where much original research in infectious diseases is aired for the first time. This was in Washington, D.C. An abstract of this presentation is published in their Proceedings of that year.
In the 50's and 60's, three different epidemics of a painful vein disease occurred and were published in the medical literature's. I believe that EPIDEMIC PHLEBODYNIA, the term that was given this disease, is probably a milder form of IVN It too had severe pain, headaches, but not nearly as many features as in IVN and ME/ENM. It has not been reported since the 1960's.
In 1985 two scientific papers were published on so-called Chronic Epstein-Barr virus disease. At the same time, an epidemic of a strange, viral like disease took place at north Lake Tahoe and the researchers there promptly named it chronic EB virus disease. When this occurred, I had misgivings and did not believe this was the case. EB virus disease is manifested in infectious mononucleosis, the most common form of EB virus disease (other types exist, but they occur in severely immune deficient people). The reason I did not believe it was because my patients with IVN, whom I had followed daily since 1975 - some of them developed infectious mono well after the onset of IVN. I witnessed the infectious mono to come and go, but the IVN remained the same unto this day. So I reasoned that the outbreak at Lake Tahoe was probably a variant of IVN or the same identical disease, and if this be so, the disease could not be due to Epstein-Barr Virus.
Finally, all experts in the field across the country came also to realize that so-called chronic EB virus disease was not due to EB virus at all.
In 1986, the National Cancer Institute discovered a new human virus that they first named HBLV and then renamed HHV6 or HUMAN HERPES VIRUS NO.6. Then the opinion prevailed that HHV6 was the cause of the Lake Tahoe outbreak. But this did not prove to be the case epidemiologically and this theory has been largely discarded at this time.
In 1988 the Communicable Disease Center of Atlanta, Georgia convened a symposium of many prominent researchers on this disease, across the country. The name Chronic Fatigue Syndrome was coined and criteria were established to diagnose this disease.
How is the CHRONIC FATIGUE SYNDROME different from IVN? I believe it is the same disease, although no vascular features are mentioned in the scientific writings thus far published. Yet many of you who are examined by me exhibit the same features as my original patients from 1975 with with evident vascular features. In all of you I find evidence of inflammation of deep veins.
My original 1975 cases, as time has elapsed - years - have less evidence of superficial venous involvement and now resemble most of you whom I see for the first time. Aside from that, you fulfill all the criteria for those who are labeled "CHRONIC FATIGUE SYNDROME". But I make my diagnosis on physical examination as well as history, unlike others working in this area.
The viral agent responsible has not yet been identified. In 1975 cultures of all kinds were submitted, to test for all known viruses, bacteria and rickettsiae and they were all negative. It is a difficult agent to culture. There are some who believe that this disease could be caused by a partial or incomplete virus. The truth at this time is not known.
The description of the disease above describes the more severe cases. There are those of you who have milder cases and expressions of this disease. Some of you for instance, have only mild exhaustion and extremity discomfort. There are those of you who have mild disease and when you have a remission, feel virtually normal. At least in the more severe types, IVN appears to be a lifelong disease. The general tendency is for patients to gradually improve.
While there is presently no cure for IVN, a great deal can be done to help patients cope with the distress caused by this disease. It is also very useful for you to know what you have, for if you know what you are up against, it is HALF THE BATTLE WON! There are medicine's that do help.
UPDATE, SEPTEMBER 1990
It has been my contention since 1975 that, a new and difficult to cultivate virus causes this disease. In 1975, we attempted to isolate a virus from human sources, throat swabs, mouth washes and stool samples. We checked for evidence of all known living agents and viruses that might cause such a disease. Nothing grew in tissue cultures, suckling mice and no antibodies were found against all possible known viruses, including EBV (Ebstein-Barr virus), Coxsackie virus and many others. I further have consistently stated that this virus is communicable person-to-person and that close family members and associates could harbor the virus, but not be ill. My guess was that this might be a new retrovirus.
Recently at the Wistar Institute of Philadelphia, Dr. Elaine DeFreitas was able to show a virus that most closely resembles HTLV-2 in 10 of 12 Chronic Fatigue Syndrome patients who were adults and 14 out of 19 children studied. Bear in mind, however, that she did not actually isolate the virus. She also used in situ ybridization of find DNA sequences complementary to viral messenger RNA probes in lymphocytes, the white cells infected by HTLV-2. But this is not proof positive that this virus causes the chronic fatique syndrome (infectious venulitis) . Additional work must be done to prove it. Nevertheless, it is the most exciting lead as yet and HTLV-2 may indeed be the virus we have been looking for. What is HTLV-2, or human T cell lymphotrophic virus? It is a retrovirus, a peculiarly formidable family of viruses. Now, Herpes viruses (Chicken pox-shingles, Herpes simplex (or cold sore virus), Cytomegalo virus, EBV virus (Epstein-Barr or infectious mono virus ), HHV6 (human herpes virus No. 6 ) and HHV7 appear to infect all of us and that is why it is so difficult to grow retroviruses. The Herpes groups rapidly destroy the cells and one can't see what the retrovirus effect is doing. So, a direct approach to grow retroviruses does not work.
HTLV-1 causes a type of leukemia (hairy cell leukemia) and tropical spastic paraparesis, a chronic neurological disease. As you know, HTLV-3 or HIV causes AIDS. But thus far, HTLV-2 has been associated with no disease, unless this new association with the chronic fatique syndrome holds up. It is interesting that DdFrietas found HTLV-2 in family members and associates who were not ill. I have said for many years that the unknown virus was carried latently, that is, without disease in family and close associates. My studies have indicated this for a long time. Many researchers believe that perhaps more than one virus is involved including EBV and HHV6. The British believe that Coxsackie are not involved. Only time and further studies will reveal whether HHV6 plays any causal role in an ancillary manner.
The exact identity of this retrovirus is unknown. It is unidentified. Four teams around the world are studying it. It shows up in my 1975 Mercy San Juan patients as well as recent cases, indicating that the 1975 epidemic was indeed a variant of the chronic fatique syndrome. While HHV6 is shown to be actively replicating in patients with CFS, there is nothing to suggest it is the cause of the disease. High titers can be found in normal people.
Retype with permission given by DR. ERICH D. RYLL
BY Jocelyn N. --LVN
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