Caroline herself has been looking for answers for decades and her fight, fraught with misdiagnosis, confusion and even doctor neglect, has been every bit as tumultuous. Unlike many people with ME/CFS, however, it does have a happy ending and the reason for that is Doctor Dantini.
Carol’s treating physician, Dr. Dantini, demonstrates how large and diverse the CFS/FM universe is. A Florida physician treating FM and CFS with antivirals since the late 1980′s, with a book “The New Fibromyalgia Remedy” out in 2008, and a website touting the viral causes and treatment of FM (and CFS) – I was kind of astonished I?d never heard of him.
His website states that ” He specializes in the treatment of viruses that cause fibromyalgia(FMS)and chronic fatigue syndrome(CFS)” and that “The advantage in diagnosing the viral cause of fibromyalgia(FMS)and Chronic Fatigue Syndrome (CFS) leads us to a logical course of treatment based on laboratory diagnostics.”
As he relates in his story Dr. Dantini had classic gradual onset FM/CFS. An ear nose and throat specialist and surgeon he slowly got more and more tired. First he put a couch in his office so he could take naps. Then he began getting headaches, night sweats and irritable bowel symptoms and his muscles and joints felt heavy, weak and painful. The worst for him, though, was the exhaustion. He tested positive for herpesviruses and six months of high dose antivirals and watching his food allergies left him healthy again.
Now he runs an ear nose and throat and FM/CFS clinic. His treatment protocol consists mostly of antivirals and allergy treatments. His website states his fibromyalgia protocol doesn?t work for everybody but has an 80% ‘success rate’.
Survey - In a survey of 25 patients in his book the treatment duration ranged from six to 17 weeks. Their year of onset ranged from 1975 to 2003.Their average self-reported ‘health score’ at the start (1-10) was 1.92 and at the end was 7.64. Although Dr. Dantini reported that younger was better the one person with a 1975 onset went from a 1 to a 9 and a person with a 1980 onset went from a 2 to an 8. Four out of the 25 improved little or at all.
In his book he states that once food allergens and viruses are treated 75% of his patients ‘respond fully’; their energy levels return to normal, their pain is gone (unless they have a pre-existing condition), their ability to sleep and concentrate improves and they are able to stop their pain and anti-depressant medications.
Outside of the Box Viral Testing and Treatment
Physicians are taught that IgG results have no bearing on whether an infection is active or not but Dr. Dantini, Dr. Lerner and Dr. Montoya. All believe that very high IgG levels in the presence of illness often do reflect an active infection. Dr. Dantini believes antibody titers about 4 times what is considered normal – reflect an active infection in a person with the symptoms of ME/CFS/FM.
|Antibody||Normal||Dantini – Positive|
|EBV Nuclear Antigen||1:10||1:40|
|EBV Early Antigen||1:10||1:40|
These doctors diverge from other physicians on duration of antiviral treatment needed to be effective as well. Most herpesvirus infections in the population are quickly staunched using short courses of antivirals. Check out the prescribing information for Valtrex (valacyclovir) for genital herpes (1 gram twice daily for 10 days), herpes zoster (I gram 3/’s daily for 7 days) and CMV retinitis (900 mgs of Valcyte 2x’s/day for 21 days. ). Most doctors quail at the idea of taking high levels of these drugs for months or a year or longer. Why, they ask, would Valtrex be able to quickly stop a very visible and painful infection but not inhibit a silent one that has no visible effects?
Dr Dantini focuses mostly on famciclovir (Famvir) and valacyclovir (Valtrex) and uses ganciclovir (Centovene) and valganciclovir (Valcyte) less, because of their side effects.
He notes that dosage varies but they generally need to be higher than is used to treat fever blisters and genital herpes and he tends to use similar doses to those used to treat herpes zoster (I gram/3′s daily). If there is no response he gradually increases the dosage.
He does not claim to have found the whole answer to FM/CFS but does believe these usually overlooked viruses play a large role.
HERPESVIRUS ME/CFS SHORT OVERVIEW
Anecdotal Information - This is all very encouraging. It’s clear that herpesviruses play an important role in a subset of people with ME/CFS but the field is clearly in flux and in the need of robust studies.
Dr. Dantini reports that 75% of his patients have increased herpesvirus (or other pathogen) titers and about 75% of them respond very well to antivirals (and the removal of food allergies). Dr. Lerner asserts that high percentage of his patients have them and has produced several studies suggesting the significant benefits antivirals can bring. Dr. Montoya has had excellent success with some patients and not with others.
Dr. Chia, on the other hand, appears to find more enteroviruses than herpesviruses and Dr. Natelson reports he rarely finds herpesviruses, Dr. Nathan devotes little attention to them in his book (On Hope and Healing) – and uses transfer factor to treat them rather than antivirals. Dr. Cheney focuses more on enhancing the “terrain” than in chasing pathogens.
Studies - The HHV6 Foundation has produced an overview of past studies which suggests that almost 47% of people with ME/CFS may have an active HHV6 infection. When more sensitive tests were used the percentage was closer to 60%. Last year a Kerr study reported a much higher degree of EBV activation in ME/CFS patients relative to controls but a Lloyd study did not find increased levels of any herpesviruses.
On the treatment end the small Kogelnik Montoya study in 2005 had astonishingly good results with a significant number of people showing dramatic results but the followup placebo controlled blinded study (not published yet) was less successful. Dr. Lerner has done the most work in the field and has promising results but some researchers have critiqued his study design and statistics.
What is really wanted and needed in this field are successful placebo-controlled, double blinded studies. Montoya’s followup study was supposed to be that study but it’s less successful results plunged Dr. Montoya into a intensive analysis of the results, dose, patient characteristics , etc.. He appears to have figured some things out and will reportedly release the study findings in the near future.
Responders and Non-responders - I asked Dr. Dantini if there are people with high antibody titers who do not respond to antiviral treatments.
“Yes, I’m still working this out….the antiviral treatment interferes with the replication of the viruses. However, for the actual destruction of the viruses the immune system has to step in, so if you have individuals that are so down that they can’t help immunologically then the effectiveness of the medicines is marginal.”
“I have people that I’ve treated for 6 months to a year and they’re gradually improving but it?s at a snails pace because they were so sick to begin with; most of these people were bedridden, had high doses of narcotics just to control pain.”
On the other he has people who, like Carol, respond very quickly..”I have people who respond in 3-4 weeks but they’re usually people who have not been sick for a long time and they’re young? Young is a big deal.”
Dr. Montoya’s Stanford website notes that from 30-40% of patients with elevated titers do not respond to even long term anti-microbial treatments. Dr. Lerner’s recent study suggests that many of these patients may have other, undiagnosed infections such as Borrelia burgdorfii (Lyme Disease) and he proposes treating those infections could make the difference.
Non-infected group - Pathogen detection, even in this day and age, is still riddled with questions that make it difficult to assess how large the size of the non-infected group of ME/CFS patients is. Dr. Lerner and Dr. Dantini report that a large percentage of people with CFS or FM meet their criteria for infection. Hopefully the Lipkin/Montoya study which is looking at all known mammalian viruses – will provide a firmer answer to the question of pathogen frequency in the blood.
The rubber meets the road when we talk about treatment efficacy in the ME/CFS community at large. Dr. Lerner and Dr. Dantini report higher rates of treatment success than the soon to be released Montoya study will report.
Dr. Peterson has been reported to state that in his experience somewhere around 30% of people with ME/CFS will respond to antivirals, which is – assuming a 60-70% positive rate and the 30-40% non-response rate Dr. Montoya reported – fairly close to Dr. Montoya’s report. Dr. Lerner and Montoya would posit higher response rates and Dr. Lerner would note the importance of attending to non-herpesvirus infections as well.
Many questions - More clarity will require rigorous studies but there is some common ground; all these physicians appear to agree that high IgG titers can be indicative of an active infection if illness is present. They are a minority in a medical community which appears to focus on the fact that healthy people can have quite high IgG antibody levels as well.
There are too many other outstanding variables to suggest a consensus exists in other areas. Dr. Montoya believes an elevated viral antibody titer may be an indirect clue to the possibility that a virus is related to a patient?s CFS, but he is not clear as to what the threshold is and his threshold is different from others (e.g. EBV early antigen (EA) ? 160 and/or HHV-6 ? 320). Dr. Lerner appears to focus on specific antibody tests that others do not Both Dr. Montoya and Dr. Lerner look for pathogens other doctors don?t appear to look for or haven’t found(herpes simplex). Dr. Dantini, for instance, does not look for HHV6.
There is even the question of which laboratory to use and the need to assess the laboratory’s results; i.e., is it consistently reporting higher or lower than normal antibody titer levels? Montoya?s site states, “Antibody tests vary from laboratory to laboratory. The laboratory director of the lab that does your test should be able to tell you how your values compare to the median of a normal population. The laboratory director should have these statistics from studies done to license the test.”
Dosing and duration could be issues as well. Some people respond to one antiviral better than another. One person with ME/CFS had a moderate response to high levels of Valtrex but then responded very well to Valcyte – but only to high levels of that drug. Some people respond very quickly to drugs and some take much, much longer. Of course there’s the potential role Ampligen could, if it’s ever approved, play.
As part of their Research Initiative, the CFIDS Association has proposed creating standards for testing and research in order to decrease the obfuscation and put ME/CFS researchers on the same playing field. The pathogen research/treatment arena would be a great place to start. Given the plethora of results from several different sources the field shows real promise but needs a great deal more study to sort the different variables out.
More drugs are on the way - Dr. Dantini reported that the herpes virus drugs are all generic now and that wonderful incentive called the ‘profit motive’ has prompted drug companies to start working on new drugs. They are definitely needed. Some patients are simply too ill to take the current drugs at the levels and for the time needed; they can make progress but have to cut back to less than effective doses when side effects flare up. Newer, more effective drugs could mean lower doses and thus lower side effects. Better drugs could get at the infections buried deeply in the body more quickly thus cutting out really long (and expensive) drug protocols. They couldn?t come too soon for some of these patients.
Food Allergies – a Hidden Menace?
Hidden, often delayed, allergies to foods have not gotten much play in the ME/CFS Community but some doctors are convinced they play a major role not just in CFS but in many other disorders. In his book The New Fibromyalgia Remedy, Dr. Dantini states that in his experience, “identifying and removing food allergens can alleviate many chronic degenerative disorders? and related that his arthritic knee that appeared destined for a knee replacement cleared up completely after he removed food allergens from his diet.
In his book On Hope and Healing, Dr. Nathan writes that “many autoimmune diseases have a food allergy component” and that “In my experience, food allergy is one of the most commonly overlooked causes for a wide variety of conditions. ”
A Black Science - Some allergist are clear about how destructive food allergens can be but they?ve gotten no support from medical research funders in the U.S. Dr. Dantini said
It’s a black science because we have by arbitrary definition decided that, in the United States, there is no other allergy to anything you eat other than IgE which means with peanut allergy you get hives or anaphylaxis. There’s no research going on in the US. Most of the research going on is in Scandinavia or Italy.?
He believes hidden food allergies account for about 30% of his patients’ symptoms. His guess is that they arise when damaged intestinal walls (leaky gut) allow food proteins access to the bloodstream -where they prompt an immune defense. In this scenario, any food you eat regularly could prompt a strong immune response.
Viral connection - What does Dr. Dantini think causes the leaky gut? An overactive immune system caused by a virus, bacteria, yeast or protozoa or some other uncontrolled illness. He noted that some people have allergy and health problems since birth – apparently because of an impaired immune system – or an infection but many others don’t fit that mold.
When I find an individual who doesn’t have that kind of a progression; i.e., they haven’t had an allergy symptom from what I can identify and all of a sudden they begin having these kinds of problems, there has to be a reason for that. Very often they’ve contracted one of these viruses and it’s hyped up their immune system to the point where they’ve started to develop sensitivities to things in their environment.
Things get worse and worse until they take up a life of their own and if you don’t deal with those issues they don’t get totally well. I think the way to look at this is that you have a chronic infection?whether it be viral or bacterial or protozoan and your immune system is trying to fight it off and it’s not able to effectively do it so it keeps gearing up if you will…it’s like being in a Prius with a stuck accelerator. You’re accelerating down the expressway and you can’t stop it and your immune system gets more and more aggressive and after a couple of years your environment becomes toxic.
Treating the underlying infection and the allergies they’ve developed allows their immune system to calm down. I asked, “If you treat the underlying infection do you still have to treat these sensitivities or will this over-response to the environment go away?”
He said he treats both but that if you wait long enough it will all go away, (although) it is a long process, and that the fatigue problems will probably disappear first. If, for instance, a person has IBS and CFS – since IBS symptoms are often triggered by food allergies he said the fatigue problems will disappear first and the IBS symptoms will remain for a while .
Stress - What about the stress issue? Particularly with EBV ? which has been shown to reactivate with stress even in healthy individuals, the stress issue will always come up. Although he had been burning the candle at both ends, a single stressful event didn?t appear to trigger Dr. Dantini?s FM/CFS initially. After apparently fully recovering, though, he relapsed after a stressful event (death of his father-in-law). Once he went back on the antivirals he returned to health. In fact, he has had several relapses following stressful events; each time antivirals have returned him to health. If his health starts acting up again and his CFS symptoms begin to return he takes a short course of antivirals. What about stress? He said
“I hear it all the time. At that point in my life I was teaching, I had two offices, I was operating at three different hospitals. I’d be up at five am, operating at 7:30, and then off to one of my offices.”
He noted, though, that the disease cause far more stressors than anything that happens to people before it.
“the disease generates so much stress. If you can work and can’t pay your bills and you’re bedbound and you?re trying to get disability – that’s stress!?Stress in this disease is generated by the nature of the disease.”
Methotrexate? – Carol had benefitted from methotrexate and she had had CFS for decades and her recovery was astonishingly rapid (six weeks) (She is still on the medication over a year later). I wondered if the methotrexate/Famvir combination was a particularly potent one. He was not, however, a fan of using methotrexate for most patients.
“Methotrexate suppresses multiple levels of your immune system. If you take an immune suppressant like high dose steroids or Humera or methotrexate it will tend to make you feel better but is it the way to treat this? I don’t think so. I think treating any autoimmune disease with a chemotherapeutic agent is conceptually a bad idea.” The potentially serious side effects were another issue as well.
The Auto-immune Side - With all the immune activation I asked him about the auto-immune problem, and he said, I’m starting to look at this from another perspective? When someone with rheumatoid arthritis or lupus comes in and will consent to viral test he said that “curiously enough about the same percentage that have them in fibromyalgia have them in these diseases.?
These disorders are on the increase and no one knows why. I’ve been in practice now for almost 40 years. When I was in practice my training was in large hospitals and we saw a lot of stuff. You had to look long and hard..maybe you wouldnt see someone with lupus for months. We thought of them as curiosity diseases…they were an oddity, They aren’t any more.?
He suggested that increased communication and traveling has allowed the viruses that cause these disorders to spread. He also believes the reason outbreaks seem to be rarer now is that the viruses are simply everywhere.