Welcome to ProHealth’s Live Chat Q&A (held Jan. 11, 2008) with Dr. Nancy Klimas, MD – a noted immunologist and a world leader in ME/CFS/FM/Gulf War Illness research, treatment, education, and advocacy. Dr. Klimas is:
n President of the International Association for CFS/ME (IACFS/ME) – a global organization dedicated to the exchange of information about CFS/ME and FM research, care, and treatment.
n Professor of Medicine-Psychology, Microbiology, and Immunology at the University of Miami (FL) School of Medicine;
n Director of the University’s EM Papper Laboratories of Clinical Immunology and VA Gulf War Illness & ME/CFS Research Center.
Q: Doctor, I have CFS but some people just don’t believe I am really ill. I can look so normal and feel so bad. How can I convince them this is real? Is there an online source for research that we can print out to increase awareness about the depths of this debilitating illness?
Dr. Klimas: The CDC has published very convincing studies on this exact question. They have shown that CFS/ME patients can experience a level of disability that’s equal to that of patients with late-stage AIDS, patients undergoing chemotherapy, and patients with multiple sclerosis. You can find this information on the CDC and the CFIDS Association of America web pages. Here is one meant for doctors: http://www.cfids.org/sparkcfs/health-professionals.asp. The first page of the Physician Toolkit quotes the CDC’s Dr. William Reeves on this subject.
Q: Do you feel Chronic Fatigue Syndrome and Fibromyalgia are one and the same?
Dr. Klimas: No, though there is considerable overlap. I don’t even consider all ME/CFS the same – there are subgroups, and subgrouping is going to be the key to effective therapy. There are already biomarkers in development that will tell both FM and CFS apart and define the overlapping groups – as well as studies to develop the biomarkers that distinguish different subtypes of CFS.
Q: Doctor, what do you think of Dr. Jonathan Kerr’s gene expression findings? [See “Seven genomic subtypes of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis” published in December 2007.]
Dr. Klimas: It is very exciting! His data, and that of Dr. Vernon, should lead to both biomarkers and treatments that are individualized. [Dr. Suzanne Vernon, PhD, was recently named Scientific Director of the CFIDS Association. A research team she led in her previous work at the CDC identified three genetic variations in ME/CFS serotonin synthesis that correlate with different measures of disability and fatigue.]
Q: What do you think of the Sakudo diagnostic blood test for CFS using visible and near-infrared spectroscopy? Have you heard any news as to progress on this?
Dr. Klimas: Dr. Sakudo, a researcher at Osaka University, presented additional data at a meeting I attended in Scotland last summer – the International Conference on ME/CFS Biomedical Research. It’s still looking good.
Q: Any thoughts on Dr. John Chia’s findings on enterovirus in stomach biopsies, published last fall? [An enterovirus is defined as “a virus that enters the body through the gastrointestinal tract and thrives there, often moving on to attack the nervous system.”]
Dr. Klimas: Isn’t that interesting! Dr. John Gow at the University of Glasgow had some early data suggesting enterovirus in the muscle, but it didn’t really pan out. Now we have this important study on the gut! Shows how important it is to look in every type of tissue.
The main thing here is to remember that when the immune system lets one virus out, it can let out many – and antivirals directed at HHV-6 (Human Herpesvirus 6) and EBV (Epstein-Barr virus) aren’t going to work on enterovirus. Of course, I am an immunologist and believe immune boosting drugs may be very important.
Q: Dr. Klimas, do you know much about Dr. Gow’s recent research? It seemed to be showing promise a few years ago, but I have heard nothing recently.
Dr. Klimas: Last time I spoke with Dr. Gow, he was working on a genomics project, and had some pretty cool data. I haven’t heard him talking about enterovirus for a while.
Q: Is your hunch that this is a viral and/or bacterial illness (or illnesses) that is still active in patients, or do you think that it is a “hit and run” attack on the brain?
Dr. Klimas: Oh, both I think. It’s all back to subgroups with this question. I know that there are patients with reactivation viruses active right now (look to Dr. Dan Peterson, Dr. Martin Lerner, and Dr. Jose Montoya for their work in HHV-6 and EBV infection). And enterovirus reactivation is a worry (see Dr. Chia’s study on this subject). That does not mean these pathogens started the process – but that they help maintain it.
Q: I have been ill since I had mono 10 years ago. Why am I still sick when others recover completely from mono?
Dr. Klimas: A recent prospective study found that the one single predictor of who is going to stay sick after a viral infection is the severity of the initial viral infection. Patient advocates have been happy to note that there were no psychiatric predictors.
I suspect that the most important factors are a combination of genetics, immune function at the time of the inciting infection, and the inciting virus itself. The virus that causes mononucleosis (Epstein-Barr virus – EBV) is particularly tough on the immune system.
Q: My chronic fatigue illness started with infectious mono. After about a year, a very low vitamin D level was discovered. My doc thinks that this played a role in my immune system failing to contain EBV. Are there any references on this?
Dr. Klimas: Low vitamin D is a frequent finding even in my sunshine state – Florida – and vitamin D is important to immune health. But I don’t now if it was there to begin with or is a consequence of the illness.
Q: Is it possible to have recurring bouts of EBV?
Dr. Klimas: There have been studies that show viruses at high levels during relapse and low during relative good times – mostly HHV-6 though. (Konnie Knox, PhD, at the Wisconsin Viral Research Group, did this work.)
Q: The glands under my ears are often tender and sometimes visibly swell up. What could be causing this?
Dr. Klimas: There are lymph nodes there and your parotid glands, which help make saliva. Epstein-Barr virus loves to hang out in parotids…
Q: Are you optimistic with regard to Dr. Montoya’s work with the antiviral drug ValcyteTM [generic name valganciclovir] – its ability to help a subset of ME/CFS patients with chronic HHV-6 and EBV infection? And if so, do you agree that a positive correlation in his study, if found, will go a long way in legitimizing this illness?
Dr. Klimas: The first research to achieve an FDA label on any drug will go a long way to legitimize this illness – look at LyricaR and FM! [Lyrica was the first prescription drug to receive FDA approval.] But it would be gratifying if that first label were on an antiviral or immunomodulator.
Q: When will the results of Montoya’s phase 2 trial of valganciclovir be published?
Dr. Klimas: I am hoping they will finish the data collection part of the study by June 2008 – but analysis and publication take time!
Q: Treatments you are currently using or see possibly being helpful in the near future? How soon?
1. I am still hopeful that the IsoprinosineR company, Newport Pharmaceuticals, will move on the Phase 3 trials. [Results of the Phase 2 trial in Canada were summarized in the 2003 article “Clinical Improvement in Chronic Fatigue Syndrome is Associated with Enhanced Natural Killer Cell-Mediated Cytotoxicity”.]
2. AmpligenR is at the FDA asking for a label. [Ampligen is believed to support upregulation of the immune system’s RNase-L response to viral infection.]
3. By subgrouping, ME/CFS patients with elevated cytokine TNF-a may be directed to protocols using TNF inhibitors or blockers. [TNF – tumor necrosis factor – promotes inflammatory response. Jonathan Kerr, MD, PhD, director of a large ME/CFS human and viral gene expression study in the UK, announced at the 2007 IACFS/ME conference that he was engaged in a trial of the TNF-a inhibitor, Etanercept (EnbrelR), in a select number of CFS patients.]
Q: Is there any test that you consider promising to diagnose ME/CFS?
Dr. Klimas: Yep – the exercise physiology group at the University of the Pacific Fatigue Lab presented data at the IACFS/ME conference on next-day decreases in exercise capacity after an exercise stress test. It’s a great model, and we are taking advantage of it! [The report, just published, is “Diminished Cardiopulmonary Capacity During Post-Exertional Malaise.” A companion study – “Legal and Scientific Considerations of the Exercise Stress Test” – analyzes the test’s potential use for disablity insurance purposes.]
Q: What is your impression of the drug LyricaR for Fibro treatment? Or any other meds you recommend?
Dr. Klimas: I like Lyrica, or sometimes gabapentin – which is a lot cheaper – for pain management, which in turn can help sleep. [Gabapentin – brand name Neurontin – no longer has patent protection so is available as a generic.] I always start with sleep management, as restorative sleep is key to any improvement. There is a Fibromyalgia study underway using a stage 4 sleep inducer, Xyrem, which I believe is very promising.
Q: Thoughts on low growth hormone in CFS?
Dr. Klimas: This is an important observation, though it could result from poor quality stage 4 sleep. I would not consider a treatment plan using growth hormone unless sleep has been addressed and the growth hormone was so low that it met criteria for Adult Growth Hormone Deficiency.
Q: Doctor, can you give us your best sleep remedy?
Dr. Klimas: Magic pills…everyone wants a magic pill. It’s just not that easy. But sleep can be worsened by many sleep remedies – particularly valium-like drugs such as RestorilR (generic name temazepam). Some of the newer drugs hit these same receptors – like LunestaR.
I think if you wake up exhausted you need a sleep study in a sleep lab – first to rule out things like apnea, but also to document the need for stage 3 and 4 sleep. Then treatments exist to address these problems.
Q: Why would my fatigue come and go? It is not related to my sleep. I sleep very well every night.
Dr. Klimas: It is the nature of this illness to have good days and bad, and they are not always related to the quality of sleep. We have a study going on at our research center which we call the “Good Day/Bad Day” study, trying to figure this out.
Q: I dream every night and when I wake up I’m so tried. Am I getting good sleep?
Dr. Klimas: Get your doctor to refer you to a good sleep expert – I often suggest a neurologist, as they are thinking about central (brain) causes for sleep problems. Though the key is to have a doctor who is willing to manage and not just diagnose.
Q: What approach do you use with your patients who suffer from sensory overload? [Dysfunction in sensory information processing – “hypersensitivity.”] I use meds for my FM pain, with supplements, rest, & exercise for CFS exhaustion. I try to avoid situations that might trigger Multiple Chemical Sensitivity & I try to be conscious of my body for my hypermobility syndrome. But sensory overload has the most devastating impact on my life & there is no controlling the surges of pain, nausea, migraines, dizziness, etc. I’ve found very little on sensory overload in the literature, my doctors haven’t a clue, & I would greatly appreciate any thoughts from you, Dr. Klimas.
Dr. Klimas: Great question! Sorry for a poor answer full of maybes. We have no studies on this, though there have been a few in the Multiple Chemical Sensitivity literature. I think Dr. Iris Bell at the University of Arizona Program in Integrative Medicine has some publications on this question. .
I also wonder if the patients with this problem are the ones with the most neuro-inflammation…suggesting a Central Nervous System low grade infection or autoimmune process. We could use some PET scan research studies to sort this question out.
Q: In 1997 you co-wrote a book with Dr. Daniel Peterson and others titled Disability and Chronic Fatigue Syndrome: Clinical, Legal and Patient Perspectives. (It included sections on Long Term Disability for CFS/Social Security Disability.) Are there plans for an updated version or new book?
Dr. Klimas: Not at this time. I edited the book after an excellent session of the IACFS/ME meeting on that topic. I’ll mention the possibility to the meeting organizers for next year’s meeting.
Q: The 1997 Disability & CFS book stated that: “As the CDC has acknowledged, the vast majority of patients recover in the first two years following onset of the illness and are unlikely to recover after five years.” Do you still believe this to be true?
Dr. Klimas: No. The data are not holding up, and as newer treatments come into play, patients with long duration illness should have more hope for improvement or recovery.
Q: Should CFS patients try to boost – or diminish – their immune responses?
Dr. Klimas: A loaded question – you want better antiviral function, but less inflammation and immune activation. That’s not easy, and immune-based therapies have to be careful not to immunosuppress.
Q: What tests should be done for dysautonomia in a CFS/ME patient? [Dysautonomia, or autonomic dysfunction, involves problems with/instability in the central nervous system’s regulation of many “automatic” functions, from blood pressure and heart rate to body temperature and digestion – and can involve a wide variety of symptoms.]
Dr. Klimas: I start with a week of blood pressure and pulse logging – flat, upright after 5 minutes… If there is more than a 20 mm difference in blood pressure or pulse, then I order a tilt table test, or treat for dysautonomia.
Q: I have orthostatic intolerance, which is worse than the fatigue. Any suggestions? I tried FlorinefR and it was a big mistake. I got high blood pressure, and getting off it gave me nerve pain. [Orthostatic intolerance is a type of autonomic dysfunction common in ME/CFS where rising from a prone to upright position is associated with symptoms including abnormal drop in blood pressure, fast heartbeat, faintness, etc. Referred to as Postural Orthostatic Tachycardia Syndrome (POTS).]
Dr. Klimas: Sometimes it takes a combination of a beta blocker and Florinef in this case. Particularly if you have episodes of fast heartbeats. Remember, your blood pressure is highest LYING DOWN! So make sure you don’t have high blood pressure then. [Florinef, generic name fludrocortisone, supports salt retention & can help prevent blood pressure from falling. Beta blockers slow the nerve impulses that travel through the heart so it needs less blood and oxygen and doesn’t have to work as hard.]
Q: Dr. Klimas, I get attacks of very fast heartbeats when I go to bed and they make me very anxious at times. Do you find this is common? Luckily a beta blocker does help.
Dr. Klimas: Very common. It’s that darn autonomic instability. If you are female, menopause will not be fun.
Q: My daughter has autonomic dysfunction as part of her CFS. Who aside from yourself would you say is most knowledgeable about this?
Dr. Klimas: The wizards include Dr. Peter Rowe, MD, at Johns Hopkins, as well as the group at Vanderbilt Medical Center’s Autonomic Dysfunction Center for treatment and research, and Columbia University.
Q: Is orthostatic intolerance necessary in a diagnosis of CFS?
Dr. Klimas: No – only 60% or so have this.
Q: Are you disappointed with the empirical CDC definition for CFS that is so broad that it covers 2.54% of the population?
Dr. Klimas: Wow what a loaded question! It is important to know that such a high percent of the population suffer from severe fatigue. In Japan it is closer to 5%! But in that very high number are the various subgroups.
Q: So more people have it than we are aware of?
Dr. Klimas: Absolutely! And less than 15% of patients who have ME/CFS have been diagnosed.
Q: Overall, do you think the immune symptoms of ME/CFS are more about ongoing viruses or some type of immune dysfunction or a combination of both? Or perhaps dependent on the particular person?
Dr. Klimas: Every patient is different, and the immune system problems could result from (and lead to) persistent viral reactivation, or could come from a more autoimmune-based problem.
Q: Dr. Klimas, do you think we are close to cracking the cause of this illness?
Dr. Klimas: Yes, I do. I think the genomics studies have given us amazing insight into the causes and potential treatments of this illness.
Q: What would you recommend for muscle/tendon tightness in the hands?
Dr. Klimas: Muscle tightness and spasms need to be treated with regular stretching exercises, cold compresses – though sometimes heat works. Exercise can be difficult for ME/CFS patients. Dr. Charles Lapp, Director of the Hunter-Hopkins Center in Charlotte, NC, showed that low-level aerobic exercise can be tolerated in 5-minute bits, with 5 minutes of rest between each attempt. This can be very helpful! So aerobics in small bits, resistance exercise, and stretching, all three.
Q: Do you know any site for a good muscle strengthening program for people with fairly severe CFS?
Dr. Klimas: The key is to go gently, go slowly, and rest between efforts. I suggest a Pilates for mats DVD and a 5-minute timer. Come back off and on during the day and try to do another 5 minutes. Denise Austin has a nice tape that my patients like a lot.
Q: I get good days and bad days. Would my daily exercising & stretching contribute to my added fatigue? I do Pilates and yoga. Denise Austin too. I even worked with a physical therapist to ensure I am stretching properly.
Dr. Klimas: You can overdo exercise – and relapse (it’s in the diagnostic criteria for the illness, after all). You can recondition to the point where you can do more. But then you push a little too hard and slide down a bit. I know it’s frustrating!
Q: Who, other than you, is doing the best work around treatment, diet, etc. What hospitals are the most open to/knowledgeable about CFS?
Dr. Klimas: It’s hard to find good doctors. Most do not know much about CFS. Co-Cure (the Co-Cure ME/CFS & Fibromyalgia Information Exchange Forum) keeps a nice list on their web page.
Q: I am in Sarasota Florida. Are you seeing new patients, and accepting them for studies?
Dr. Klimas: Not right now. But I hope to open the door again soon, as my university plans to hire new staff that would expand our program. We are recruiting for our Good Day/Bad Day study, and a biomarker discovery study. I also need veterans with CFS, and healthy controls.
Q: Doctor, do you believe in remission of the illness?
Dr. Klimas: Absolutely! And complete resolution! It happens, but not often enough to make promises. I get the best hugs on airplanes and other public places when I bump into patients now healthy and happy.
Q: Do you believe there could be a connection between the effect of ME/CFS on the immune system and the fact that I and other patients I know don’t seem to come down with colds, or shake them off more quickly?
Dr. Klimas: Two reasons – first you do isolate more, and may avoid exposures. But I think the bigger deal is that you up-regulate interferon – your body’s natural antiviral – which can stop an infection before it takes off.
Q: Do you ever see neutropenia (a low number of infection-fighting white blood cells) in your patients?
Dr. Klimas: Yes, and then I worry about bone marrow suppression, pesticide exposure, medication or supplement side effects, etc.
Q: Any thoughts as to the role of environmental toxins like mold?
Dr. Klimas: Anything that over-stimulates the immune system is suspect, and some molds also give off immunosuppressant factors. Another potential subgroup of CFS… I have seen sick building syndrome cases that are almost certainly working through this mechanism.
Q: Do you believe that ME could be an autoimmune illness? I’ve noticed that a lot of ME patients also suffer from hypothyreosis (hypothyroidism) and Fibromyalgia.
Dr. Klimas: The Scripps Research Institute was looking at autoimmunity in CFS for many years. They found particular types of ANA (antinuclear antibodies that attack normal tissues) in CFS.
Q: Hello Dr. Klimas – Can you comment on the effects of CFS on pre-existing hypothyroidism? My TSH levels have been fluctuating dramatically over the past 3-4 years. [High levels of thyroid-stimulating hormone (TSH) often indicate an underactive or “unresponsive” thyroid or too little thyroid hormone, and vice-versa.]
Dr. Klimas: The data would suggest a bit more risk to women with preexisting thyroid disease despite having normal thyroid levels on replacement hormone. I add CytomelR, or switch patients to ArmourR when I am having trouble keeping their TSH pegged at 2 (optimal).
Q: My body temperature cannot seem to regulate itself. I can’t cool down in the summer and cannot warm up in the winter. Is this typical of CFS?
Dr. Klimas: It can be – but also of a thyroid or adrenal problem, so it needs careful evaluation by your doctor.
Q: What are your thoughts on Adderall for fatigue?
Dr. Klimas: Adderall is one of many stimulants doctors use for the symptom of fatigue. A very small study was presented at our last research meeting suggesting RitalinTM was helpful in 40% of patients. But I have had a patient become suicidal after a single dose, so use stimulants very sparingly.
Q: Doctor, what do you think of patients taking cortisol – either prescription “Cortef” or in over-the-counter adrenal glandular supplements? [Cortisol is a hormone produced by the adrenal gland and referred to as the “stress hormone” because it is involved in fight or flight stress response – raises blood pressure, blood sugar, etc. Studies have found it is low in about a third of ME/CFS patients.]
Dr. Klimas: Cortisol was helpful in clinical trials, but the patients could get back off once they felt better. Long term use can cause osteoporosis, cataracts… so I don’t recommend it.
Q: What is your experience with guaifenesin,
Dr. Paul St. Amand’s suggestion?
Dr. Klimas: Many patients will try guaifenesin for Fibromyalgia. My patients haven’t seen a lot of improvement, though I know Dr. St. Armand has a special [salicylate-free regimen] that goes with the treatment. It hasn’t had a proper clinical study as yet.
Q: Getting back to genomics, other than Dr. Kerr, is there research/treatment that you are particularly hopeful about?
Dr. Klimas: There is a Spanish company that is going forward with the FDA for a biomarker they have identified that distinguishes ME/CFS from FM from healthy controls. They just opened a U.S. office. That is pretty darned exciting! [Their genetic profiling study “Genetic Profiles in Severe Forms of Fibromyalgia and Chronic Fatigue Syndrome” concluded that “FM and CFS are different diseases with distinct genetic profiles.”]
Q: We need help in Canada. There are no known MDs to help ME/CFS patients. Do you know of any? Thanks.
Dr. Klimas: Dr. Bruce Carruthers published the international ME/CFS (and FM) clinical case definition; Dr. Alison Bested is there; and Dr. Ellie Stein – all heroes in my mind. [Dr. Bested (an author of Hope and Help for Chronic Fatigue Syndrome and Fibromyalgia) is affiliated with the Environmental Health Clinic of Women’s College Hospital in Toronto. And Dr. Stein (author of a guide for diagnosing and treating anxiety and depression in people with ME/CFS) sees patients with ME/CFS, FM, MCS and toxic exposure in Calgary.
Q: Which tests do you use to distinguish between CFS & depression?
Dr. Klimas: Depression can be a lifelong problem, or a consequence of a chronic painful and debilitating illness like ME/CFS. Half of ME/CFS patients will develop depression AND IT IS ABSOLUTELY TREATABLE. There are common instruments (Beck depression inventory, Hamilton-D) that screen for depression. I use them and then ask colleagues in psychology or psychiatry to help me sort it out and treat when appropriate.
Q: Hi, I am a doctor. I was wondering what is the pathophysiology of Chronic Fatigue Syndrome. I am sorry if this question has been asked before. Is it mostly endocrine, or autonomic nervous system?
Dr. Klimas: It is a complex mix of immune, HPA axis, autonomic and sleep dysfunction. It is treatable, and patients really can get healthier with a careful stepwise approach. Go to http://www.iacfsme.org for more info.
Q: Dr. Klimas, I know one of your key goals as an educator is to disseminate the latest evidence on our illnesses to the provider community. The CFIDS Association has announced that it will not be applying for a renewal of its contract with the CDC for services to educate healthcare professionals on ME/CFS diagnosis and management. “Based on concerns about the direction of the program.” Can you comment on this?
Dr. Klimas: Well I can’t. But I can tell you that the IACFS/ME is extremely keen to develop very detailed guidelines to help primary care providers work through the many complex problems that face CFS/ME patients. [See Dr. Klimas’s letter to the IACFS/ME on “The Need for Treatment Guidelines”.] I think the national awareness campaign was a great first step, and hope that the IACFS/ME can work with the CFIDS Association and other advocacy groups to reach more and more providers.
Q: For someone wanting to provide info to their MD that the doctor would respect concerning the organic abnormalities in CFS – what source do you recommend? The CDC info is in lay terms.
Dr. Klimas: I just published a nice review in Current Rheumatology Reports – out in December, on important research findings in the past year: “Chronic Fatigue Syndrome: Inflammation, Immune Function, and Neuroendocrine Interactions.”
And the IACFS/ME webpage/ links professionals to a number of very helpful reports and articles. Web committee chair Lee Meisel, MD, and the staff of the IACFS/ME have worked long and hard to keep this up to date and useful. Also, as I mentioned, the Toolkit on the CFIDS Association webpage is very helpful. http://www.cfids.org/sparkcfs/health-professionals.asp
By the way, the IACFS/ME needs patient members to support our professional organization and keep us alive and kicking. As the President, I ask you to please join, and keep up with research and clinical advances through our newsletter, conferences, etc. A membership application form for both professionals and “associate” students, patients, and other interested individuals or groups is available at the IACFS/ME website
Our live chat is now drawing to a close. We thank Dr. Klimas for her remarkable generosity in being here today. And we thank all of you for contributing to this very interesting exchange.
Doctor, you mentioned getting hugs from patients in public places. I will send big hugs and thankfulness from all of us who do not get well on our own. Your research and what you do is much appreciated!
Dr. Klimas: Thank you! Thank you, everyone, for such a lively discussion! I wish you all a happy and healthier 2008! And thanks to ProHealth for keeping this going!
You can read a German translation of this Q&A, by Regina Clos, editor of CFS/ME-Actuell, at http://www.cfs-aktuell.de/februar08_1.htm
Note: This information has not been evaluated by the FDA. It is generic and is not intended to prevent, diagnose, mitigate, treat, or cure any illness, condition, or disease. It is very important that you make no change in your healthcare plan or health support regimen without researching and discussing it in collaboration with your professional healthcare team.