Chronic fatigue syndrome: Gradually figuring out what’s wrong

Anthony Komaroff, MD

Editor in Chief, Harvard Health Letter

In 1983, a health professional in her 30s walked into my office and said, “I’ve been healthy all of my life. A year ago, I came down with some kind of virus — sore throat, aching muscles, swollen lymph glands, fever. My fatigue was so bad I was in bed for nearly a week. Many of the symptoms gradually improved, but the terrible fatigue and difficulty thinking have not gotten better. They’re so bad I can’t fulfill my responsibilities at home or at work. This illness is affecting my brain, stealing my energy, and affecting my immune system. It’s keeping me from realizing my dreams.”

There’s a piece of advice attributed to a famous physician, William Osler, that every medical student probably has heard: “Listen to your patient. The patient is telling you the diagnosis.” But I wasn’t sure it applied in this case.

What we knew then

First of all, the textbooks of medicine didn’t describe an illness like this. In addition, all the usual laboratory tests to screen for various diseases came back normal. At this point, a doctor has two choices: decide to believe the patient and keep searching to find what is wrong, or to tell the patient, “There is nothing wrong.” Indeed, some doctors seeing people like my patient did just that, adding insult to injury.

Fortunately, many physicians and biomedical scientists around the world became interested in this illness, and over 9,000 scientific studies have been published in the past 35 years. The Institute of Medicine has concluded that the condition, now called myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) “is a serious, chronic, complex systemic disease that often can profoundly affect the lives of patients.” It affects up to 2.5 million people in the United States, and generates direct and indirect expenses of approximately $17 to $24 billion annually.

What we know now

As I discussed in a recent article in the journal JAMA, research has documented underlying biological abnormalities involving many organ systems in people with ME/CFS, compared with healthy controls. Here’s an overview of what the current science suggests.

The brain. Tests of brain hormones, formal tests of thinking, magnetic resonance imaging (MRI), and positron emission tomography (PET) scans of the brain are abnormal in a substantial fraction of patients with ME/CFS. Tests of the autonomic nervous system, which controls vital functions including body temperature, blood pressure, heart rate, breathing rate, and movement of the intestines and bladder, also are abnormal. Not all of these abnormalities of the brain are present in every person with ME/CFS, and they appear to come and go.

Energy metabolism. We are alive because the cells of our body are alive. And they’re alive because they can make energy, and use that energy to do their jobs and remain alive. Our cells make energy out of the oxygen in the air we breathe, and out of the sugars, fats, and proteins we eat. In ME/CFS, research has shown that the cells have trouble both making and using energy. That is, people with ME/CFS feel they don’t have enough energy because their cells are not making enough, nor using what they make efficiently. The ability of cells to extract oxygen from the blood and use it to make energy appears particularly defective after physical and mental exertion.

Immune system. The immune system is complicated, containing many different kinds of cells that make many different kinds of chemical signals to talk to each other. Hundreds of studies have found evidence that in people with ME/CFS, the immune system is chronically activated, as if it is fighting something, and that parts of the immune system are exhausted by the fight.

Activation of “hunkering-down” systems. Animals, including humans, have systems to protect them during times of major threats. For example, worms and bears that are faced with a shortage of food “hunker down”: they activate systems that focus the energy they are able to make on the processes necessary to stay alive. Nonessential, energy-requiring activities are minimized. Humans who are seriously injured or sick also activate various hunkering-down systems. Some evidence suggests that in ME/CFS the hunkering-down systems may have been turned on, and remain inappropriately stuck. Research teams are trying to figure out how to turn off the hunkering-down systems.

Continued research should lead to better understanding and treatments

A great deal more is known about ME/CFS today than 35 years ago. With continued and expanded support from the NIH, CDC, and private foundations dedicated to ME/CFS, I expect a lot of progress in the coming decade. Instead of doctors saying, “The tests came back normal, there is nothing wrong,” they will say, “Tests showed us what was wrong, and we have treatments to fix it.”

And doctors will recognize the wisdom of the wise advice we all learned in medical school: “Listen to your patient. The patient is telling you the diagnosis.”

Related Information: Boosting Your Energy

Comments:

  1. Ingrid Askenbeck

    Oh the memories this brings up! Trying to keep this short: I got sick on Thanksgiving day 1992. Such a horrible virus I could not possibly drive to be with my elderly parents that day. I was a 40-something single, self-supporting, athletic, mountain-climbing Social Worker very unaccustomed to being ill at all. It eventually ended with total collapse, and a 101 fever that persisted daily for four years. I have often had to educate doctors on the difference between depression and ME/Chronic “Fatigue”: With ME/CFS I can wake in the morning, thinking “this is a good day, & there are 5-6 things I really want to get done today, I’m sure I can do it”. Then I only end up having energy to accomplish maybe one thing on that simple list. With depression you wake up wishing you had not woken up at all. Thoughts of worthlessness fill your mind, convinced everyone who loves you would be better off if you were dead, and you dread having to face another day. (In Harry Potter terms, the dementors have sucked your soul right out of you, leaving only a shell of a person). In the course of ME I have experienced such a depression too. But treatment worked to make that depression go away. Not so with ME. Tomorrow is Thanksgiving day 2019 and I still battle ME. I have been unable to work, at any job. For a professional person, poverty has been the worst side effect. I have adapted by focusing on energy-conservation. That is, conserving MY energy, enough to appreciate small joys in life anyway. I am so grateful for doctors like Dr Komaroff who keep working at this disease. Thank you.

  2. Jonathan

    When I went to a holistic doctor for (what turns out to be a moderate version of chronic fatigue), first thing, he recommended a book:
    “Adrenal Fatigue : The 21St-Century Stress Syndrome”
    by James L. Wilson [orig publ 2001].
    (Also, “The Canary and Chronic Fatigue” by Majid Ali (1995). Dated and reviewers cite more recent, so of course look up others too.)
    (Aside from intensive testing…) my doctor recommended various neurotransmitter-support supplements, exercise, the obvious: regular sleep (and other things). Now, ~11 years later, I’m a bit better, holding my own.
    Every person is different, so learn as much as you can, and find doctors with good backgrounds.

  3. Mel

    Thanks … there’s hope, I guess. For those of us who have been desperately ill for 20-30 years with this and who have been through the wringer with doctors and the medical industry in every way possible, it’s kind of hard to get too damn excited.

    But thank you very much for trying. Sincerely.

  4. me patient

    Medicine is SO RIDICULOUS, taking years to believe patients, probalby centuries to find a cure for future generations, I’m sure the human species will be extinct many centuries before a cure for ME/CFS can be achieved by the ridiculous “science” of medicine, they can only insult patients, but never get any cure for anything.

  5. Frank

    Amazing read. This disease has stolen three years of my life. 27 year old male. Thank you.

  6. Cindy

    I had CFS severely for 10 years…devastating, life altering and all suffering…was wheel chair / walker bound. Dx by tons of docs including the Mayo Clinic. I have been TOTALLY well and symptom free for 3 years now. Here’s my question….why are researchers not asking the patients that fully and forever recovered what it is? Don’t ask me unless it is in a clinical setting because patients get extremely angry and down right mean when they are explained what happened. Do clinical trials on the recoverees if you can get them to admit they recovered for fear of serious backlash like I experienced. It would be an eye opening experience for the reserchers…they are going about it all wrong.

  7. Janice Johnson

    I think it’s essential to use ICC to ensure that your survey population really have ME and doesn’t include people who just have one of the many hundreds of illnesses which have chronic fatigue as a key symptom. Including people who don’t have ME-ICC buddies the water and weakens your research. I’m not implying that peopleWith those other fatigue illnesses aren’t genuinely ill, just that they don’t have ME We need to focus down on those who match ICC. If you wanted to learn about oranges you’d be foolish to then to do your research on a mixture of fruits. You’d get results that weren’t specific to oranges. Likewise with ME. If you want to learn about ME then make sure you are actually researching people who have ME. Use ICC

  8. Janice Johnson

    Please always use ICC criteria so you are sure that you are looking at people who all have ME-ICC and you don’t include people who have fatigue from one of the hundreds of illnesses that include chronic fatigue as a key symptom. Including people who don’t match ICC only muddies the water And weakens your findings

  9. Wendy

    “The brain. Tests of brain hormones, formal tests of thinking, magnetic resonance imaging (MRI), and positron emission tomography (PET) scans of the brain are abnormal in a substantial fraction of patients with ME/CFS. Tests of the autonomic nervous system, which controls vital functions including body temperature, blood pressure, heart rate, breathing rate, and movement of the intestines and bladder, also are abnormal. Not all of these abnormalities of the brain are present in every person with ME/CFS, and they appear to come and go.”

    As far as the above info (in quotes) is concerned; the reason you can’t find the relevant symptoms and/signals is because you are constantly using the wrong criteria in patient selection, wrong criteria in physical clinical diagnosis and the wrong criteria in research. You can’t keep mixing people with Encephalomyelitis in with Fatigue and expect to find the problem. This has been going on for 35 yrs and it will continue to go on for another 35 years unless you seriously start diagnosing and sorting patients correctly.

  10. Donna Mardirosian

    Is fibromyalgia in the same group of chronic fatigue syndrome. I was literally in bed for weeks with no energy and I thought I was on my way “out”. My doctor did many tests even for Lupus and final diagnosis was fibromyalgia. There is a whole body feeling with a burning sensation as well as absent energy. Any ideas

  11. Darla N

    Thank you, Dr. Komaroff, for your continued interest in this disease and for, as you usually do in your webinars and articles, breaking down this complex disease into parts so that the average person and the patient with brain fog can understand. We need many more physicians like you. I’ve had ME/CFS for 10 years.

  12. Elsie Owings

    Thank you for this summary. After battling this disease for more than 31 years, I still bump into people who say, “That’s a form of depression, isn’t it?” or “Oh, yes, it’s the weather. It’s got all of us down in the dumps.”

  13. Lama

    It warms my heart that professionals like doctor Komaroff are taking ME/CSF seriously. Hopefully the psychosomatization explanation prevalent among doctors will come to its end soon.

  14. diane lindeman

    Thank-you Dr. Komaroff for this. It is hopeful. As a 42 yr. SURVIVOR I have never given up HOPE. Diane Lindeman

  15. Chris

    I’m an RN and had never heard of ME and obviously neither had any of my physicians from the Kaiser medical system. I’d been sick for two years as other diseases were being ruled out, but no one knew what was wrong with me and I thought I was the only person who would ever experienced this! Then I discovered the Nightingale foundation and as I read about the abrupt onset and symptoms of ME, I literally shouted out loud “oh my god, that’s exactly what happened to me”! Then after not being able to tolerate sitting up for 4 years I read about POTS and went to my doctors once again and got that diagnosis after fighting to be tested!! I later learned how common it is in ME!! I should’ve been diagnosed right away I was such a classic case of ME! I was bicycling 200 miles a week and working full-time when I got the flu on 12/24/09 and descended into the hell of ME and I remain there to this day!!

  16. M D

    “The Institute of Medicine has concluded that the condition, now called myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) “is a serious, chronic, complex systemic disease that often can profoundly affect the lives of patients.”

    “A great deal more is known about ME/CFS today than 35 years ago. With continued and expanded support from the NIH, CDC, and private foundations dedicated to ME/CFS, I expect a lot of progress in the coming decade. Instead of doctors saying, “The tests came back normal, there is nothing wrong,” they will say, “Tests showed us what was wrong, and we have treatments to fix it.””

    If it took them 35 years to figure out that something is actually physically wrong and that multiple systems are affected, it will probably take them 350 years to find a cure.

    “Humans who are seriously injured or sick also activate various hunkering-down systems. … Research teams are trying to figure out how to turn off the hunkering-down systems.” Even though they know that “In ME/CFS, research has shown that the cells have trouble both making and using energy.”

    That’s a brilliant idea: trick the body into using up energy it’s trying to conserve. But then a temporary fake improvement is always better than finding out the cause so the condition can be permanently cured, right?

    $$$$$

  17. J Olson

    Please hurry! The 25% of people with ME/CFS who are severe, can’t wait a decade. Our son is in this category. He has been totally bed bound for 15 months, sick for almost 6 years. There were times that he needed to be hand fed. So many of these severe patients also have dysautonomia problems. If something could be found to allow them to sit up or tolerate light and sound, it would really improve their lives while waiting. Sadly, there are patients worse off than our son.

  18. AB

    I wonder what happened to the woman who walked into the office in 1983 – Where is she now – is she even alive?

    My own acute viral onset ME started out of the blue in 1984 and since then little progress has been made in treating the disease. There are pockets of good doctors who are willing to learn and try things but these remain out of reach of most of us.

    In the early days of my having the disease I could find good doctors like Anthony Komaroff if well enough to travel and had the money but over the decades these died or retired and there were years of having no knowledgeable medical care and it left me unable to work and support myself.

    The Berlin Wall came down, wars were fought and Presidents came and went. Time went went on but so little money was spent on research that people with ME stayed trapped in their homes. I’ve still got a makeup bag with things from the 80’s.
    I’ve still got ME.

    • Arlyn

      My story exactly, AB, down to the year of onset 1984 and the makeup bag not to mention the clothes that don’t get worn. Thanks to Dr. Komaroff for understanding and the best overview I have ever seen.

  19. azure

    “decide to believe the patient and keep searching to find what is wrong, or to tell the patient, “There is nothing wrong.” Indeed, some doctors seeing people like my patient did just that, adding insult to injury.”
    Left out the ever popular (especially for women patients) diagnosis of “it’s all in your head” followed by offering a prescription for a tranquilizer or anti-depressant.

    It’s been a long struggle for those w/fibromyalgia and/or CFS to have their symptoms taken seriously, for diagnosis acceptance and to find at least pallative treatment.

    • Rhonda B.

      You’v really poked the bear and opened a can of worms when you scratched the surface of a ME/CFS patient from ‘83.
      Apparently, with knowledge of the huge number, of mainly female sufferers in the U.S. alone, there lies an immense void of education in the medical field.
      Millions of patients are not simply told that there’s nothing wrong with us, for years and decades. We’re often mistreated by medical professionals, locked up in psychiatric wards, we lose our jobs, abandoned by friends & family due to our illness, we’re often accused of faking, etc.
      This disease isn’t some sort of inconvenience. It ruins our lives. Our highest cause of death is suicide.
      There is a huge community of ME/CFS Warriors around the globe that are literally dying for research to crack the code and solve this illness. It’s not going to take another 30 years. The time is now!

  20. Natasha

    Thank you for writing and posting this article. Awareness is growing but still too many doctors do not know how to help their patients despite evidence favouring certain protocols that help. The important factor to know and understand that ME/CFS can have different underlying causes, and testing for EVERYTHING is crucial to treatment.

  21. jimells

    “Chronic fatigue syndrome: Gradually figuring out what’s wrong”

    The first thing that is wrong is the name, as Dr Komaroff well knows, since he and associates approved it. The article conveniently overlooks that “CFS” already had the name myalgic encephalomyelitis since the 1950s, and that the WHO declared ME to be a neurological disorder in 1969. The question to ask is, why was this not in 1983 textbooks, and what is in 2019 textbooks?

    The second thing wrong is that the medical industry has *never* listened to patients, who loudly insisted from the start that the name “CFS” was demeaning and would lead to much harm. Who would call tuberculosis “Chronic Coughing Syndrome”?

    The third thing wrong is that most of the medical industry *still* refuses to listen to patients who are living (and dead) proof that the usual “treatment” of graduated exercise and psychotherapy is not only useless, but often harmful. The influential and fraudulent PACE study has still not been retracted and is still cited by the equally awful Cochrane exercise review.

    The fourth thing wrong is the way patients are treated by society as a whole. Nobody believes how incapacitated we can become or the range and severity of symptoms triggered by exceeding the “energy envelope”. Physicians refuse to understand that patients can be reduced to living in dark rooms, unable to eat, talk, or even leave their beds unaided.

    We are shunned by family and friends, fired from our jobs, denied social benefits, and denied employment disability insurance benefits. Instead of compassion and respect, we get “Everyone gets tired” and “Everyone knows that exercise never hurt anyone”.

    The fifth thing wrong is the lack of a medical specialty home. Most physicians, including specialists, want nothing to do with us. There are no “ME Treatment Centers of America” staffed by people that actually know something about the illness. Clinics and emergency rooms are unable to provide for even the most basic needs of patients, such as a quite place to lay down while waiting our turn for care.

    Note the above items have nothing to do with (contradictory) research findings or (inadequate) research programs. We don’t need to wait for researchers to solve the ME riddle in order to have informed physicians and compassion care. Every item above can be implemented now, with proper leadership. Please. Start. Today.

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