An Interview & Discussion on EMS
with Peter E. Callegari, M.D.

Peter E. Callegari, M.D.
Associate Professor of Medicine & Director of Clinical Services
Division of Rheumatology, University of Pennsylvania School of Medicine

The following interview took place on March 29, 1998. Faith, Newsletter Editor of NEMSN, conducted the interview.

Editor: Thank you, Dr. Callegari, for taking time from your busy schedule to talk with me today. Our readers who've been with us a while know that you've been doing the "Ask A Doctor" column for two years and that you were a participant in our 1996 conference in Washington, D.C. For those who don't know, let me state that you are a rheumatologist in the Philadelphia area who's treated a number of EMS patients. Let's begin by having you tell us a little about yourself and your work.

Dr. Callegari: Sure. I'm a rheumatologist here and a member of the faculty at the University of Pennsylvania Medical School. I practice general rheumatology, but I have an interest in autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, and EMS. I've been for 10 years now a member of the faculty at the associate professor level. I like rheumatology because it's a field where there are a lot of illnesses that require you being a thorough, general internist because they can affect many organs (multiple-system diseases) and at the same time, we don't have a lot of explanations about them. The field struck me as a field that it would be exciting to be a part of to try to sort out some of the explanations.

Editor: I'd like to talk about when you first began seeing patients who had EMS. Would you take us back to that time and what you were thinking?

Dr. Callegari: Well, I started at Penn in July of '88, and although a lot of people had already started complaining, I didn't see any people with EMS at that time. At the time I probably wasn't asking the right questions. We got smarter once the syndrome became more clearly defined. There were people who presented with generalized pain, muscle aches and often, skin rashes, but also at the same time had laboratory abnormalities which were somewhat unique in the sense that there was often evidence of eosinophilia which was associated with parasitic or allergic-type reactions. As the syndrome became better described, there was a real sense that we had to look back at some of our patients that we had put into ill-defined or undiagnosed illness. Personally, it was very shocking because during my residency we used a lot of L-tryptophan for varied complaints ranging from sleep disturbance to helping with pain. It was frightening, at least for me, the recollection of how many people had I treated with tryptophan during my residency, and how many had become sick? I was fortunate enough that much of the L-tryptophan I had given was in '84 and '85. There were years of separation between my residency in Philadelphia and New York where I did my fellowship for three years. Then I came back to Philadelphia in a different area of the city, so I don't know whether any of those patients I treated became ill, and I didn't have the opportunity for follow-up. It was frightening when that realization took place.

Editor: So was that in November of '89?

Dr. Callegari: Yes, when things began to suddenly hit the fan, I think many of us looked back and said, "Gee, were we involved in using L-tryptophan?"

Editor: You know, I hear from time to time about some of our people going back to using tryptophan. I believe that some of it may be prescribed tryptophan, but the rest is not. What is your opinion either way?

Dr. Callegari: To me it's very worrisome. I think that if the whole, entire explanation of EMS was related to a contaminant, which was the likelihood, you could make an argument that going back to tryptophan after the contaminant was removed should not be harmful. The concern I have is that there may be people in the population in whom the pathway where the tryptophan gets metabolized and used in their bodies may be different than in others. Those people may be prone to serotonin-related problems or tryptophan-related problems. There were lots of other people who were exposed to the contaminant, and many of those people did not develop EMS. It may be that there is an inherited predisposition toward developing problems from this family of medications. To cite an example that's been in the current press, there's been the whole thing about Redux. And you know, Redux works by dramatically boosting serotonin levels, and serotonin is one of the products of tryptophan. If you look at all the people who've taken Redux, and there were many, only some of them developed the cardiac problem. Why would just some develop the cardiac problem? It may be that the affected group has an altered metabolism, an altered breakdown pathway, an altered rate of breakdown, or is particularly susceptible to the toxicity of a serotonin booster like Redux. I'm concerned that some of the people who developed EMS may also have a predisposition or predilection for developing problems if they have too much tryptophan, and it may be independent from the injury that took place from the contaminant. But on the other hand, and this is where there may be some inconsistency in my position, I have used medications that boost serotonin in patients with EMS. And if you want to follow the argument to its fullest, should I really avoid those agents? Well, at the moment, I think that some of those agents provide a significant positive benefit to the group of people we're dealing with. I am concerned with anything that can enhance serotonin levels, yet it may be in the processing of tryptophan to serotonin where there is a problem. I have to admit that it's an area I think about a great deal, but there is not any clear-cut explanation in terms of how to reconcile those concerns, at least not right now. With research we may get a greater understanding about how drugs behave and how our bodies use them and perhaps even identify a subset of people within the population who are predisposed or more at risk for drugs that boost serotonin.

Editor: We also hear from members who are using melatonin. A few have said they use it to enhance their immune system. Aren't there dangers associated with using unregulated substances such as melatonin?

Dr. Callegari: Right, it is. That's what my problem is with over the counter supplements. I think the issues about impurities and contaminants are significant ones. I mean, when you look at drugs like Redux, you recognize that even medicines that are very well studied and where purity issues are being supervised, can cause significant problems which surprise us after being released. So I'm very concerned about using over the counter supplements where it's unclear about the certainty of the mixture or how much melatonin is present in the mixture. And you raise the issue not only about contaminants but about cross-reactivity in terms of melatonin. There are a number of studies being done right now using melatonin, particularly in an effort not to modify the immune system, but particularly in an effort to modify the sleep cycle where melatonin probably plays a significant role in our bodies. But those studies are done with purified melatonin and in a controlled fashion. And I think that when melatonin becomes released, and it likely will, ultimately, as this research progresses, or at least some derivative of it, in an effort to try to modify sleep disturbances, then it may be a useful agent. I'm just very concerned about it [being used now]. I remember at our national meeting in 1996, I talked to a number of people who really were very aggressively using over the counter supplements. They thought they were essential for their continued well-being. My only concern about that is, Is there another L-tryptophan story in it? And we may not know about it until 10 or 15 years later. I'm really loath to expose people to further potential injury who've already been hurt once by problems related to contamination. I don't think melatonin will win a role as an immune-modulating agent, but rather, will likely prove more useful as a sleep-modifying agent.

Editor: And in probably much smaller dosages than many people are taking now.

Dr. Callegari: It's difficult to even figure out what the dose is the people are taking because quality control in many cases from one batch to another is so poor that they can't guarantee the concentration from one batch to another. So, again, you're right, people take very large doses. People look at "natural" remedies as not being harmful, but there are lots of poisonous beans and berries in nature that can certainly do significant harm to us. I don't think the little label "natural" necessarily means safe. People avoid poisonous berries, and yet they're quite natural. I'm not certain that putting a label "natural" on something means that it's safer than a manufactured pharmaceutical. Chemicals are chemicals are chemicals whether you manufacture them or get them from nature, you still have the risk of developing serious problems.

Editor: Let's talk about the nature of EMS, then. It's chronic, multi-systemic, has affected women more than men, and we're not quite sure why, right?

Dr. Callegari: Right, but many autoimmune diseases, as you know, have a female predilection. Lupus in a ratio of 13:1, rheumatoid arthritis 3:1, scleroderma is probably 3:1 or 2:1 women to men. So many autoimmune diseases do have a predilection for women. It may not only be that women were more frequently exposed, it may also be that women are more susceptible to autoimmune diseases.

Editor: I maintain our database for the Network, and I think about 75-80% are women. Can you tell us what the figure was of the CDC cases?

Dr. Callegari: I think it was pretty close to those numbers. It was round about 3:1.

Editor: I am still also asked from time to time the median age of patients. I suppose you'd have to say the median age when they got sick as opposed to now.

Dr. Callegari: Yes, it's hard to look at it. The people who were most at risk 10 or 15 years ago were the people like in our lupus demographics, people in their 30s to 50s.

Editor: Would you say that the median age now would probably fall somewhere between upper 40s and lower- to mid-50s?

Dr. Callegari: Yes, that's where I'd put it.

Editor: Let's talk about EMS and autoimmunity. Is EMS really an autoimmune disease, or has it just affected our immune systems?

Dr. Callegari: Well, that's a very interesting distinction. I think that if you look at EMS, it certainly can fit a model of an autoimmune illness in the sense that the ingestion of tryptophan either alters the immune response to a degree where we begin to damage or injure tissues, or it (or a breakdown product) directly causes tissue injury. It's pretty obvious from early on in the diagnosis that there was inflammation in the skin, fascial layer, and muscle layer with a characteristic eosinophilic infiltration. Other organs were being injured by our immune response. And the question in this may be a chicken or egg question. And the question is, Sometimes we can think of autoimmune diseases as diseases that are precipitated by an injury or an event. I think an example of that in recent autoimmunity is an entity called drug-induced lupus where people who take some medication develop symptoms very much like lupus. And if you remove the medicines in those circumstances, the illnesses, because they are non-destructive and non-injurious, the manifestations of lupus begin to resolve. And, in a sense, I would view that in parallel with L-tryptophan, in that it may be viewed as an agent that precipitated or provoked an autoimmune response leading to, unfortunately, more injury. Another way you can look at it is that the tryptophan and contaminants may be directly toxic and cause an injury to certain areas. The immune system goes to investigate and "clean up" the debris at a site of injury. And if the injury is of a certain nature, the injury can continue and persist and self-perpetuate even without the agent being present anymore. The immune system becomes so focused on causing injury that, in a sense, it doesn't realize the offending agent is gone! A good example of autoimmunity is: A virus attacks the body, causing people to develop an immune response to the virus, but in some illnesses we think that the virus disappears, and the immune response is still looking for the virus and injuring tissues in an ongoing fashion. So, we can either have an agent that alters the immune response and, as such, provokes autoimmunity (like the drug-included lupus) or an agent that can cause direct injury leading to an exaggerated and persistent immune response or some other explanation. There may be a genetic predisposition to having an exaggerated and persistent immune response. These are people who are more prone to autoimmune problems. I think a segue to that is what you mentioned [elsewhere] about thyroid disease. In this country, most of the thyroid disease is autoimmune in nature (in the rest of the world, iodine deficiency and goiter is a more common cause of thyroid problems). Hyperthyroidism and hypothyroidism are examples of another autoimmune-mediated process. Most hypothyroidism is not simply attributable to aging. There are lots and lots of people well up in years who have no thyroid problems.

Editor: My sister-in-law developed thyroid disease and within a year she also developed diabetes. We have some with EMS who also have one or both of these diseases.

Dr. Callegari: Now depending on the type of diabetes, that's another type of autoimmune-related process. Likely, her diabetes was secondary, not autoimmune, but thyroid disease is virtually all autoimmune-related. So the increased incidence of thyroid problems [in persons with EMS] suggests this idea that there is an overactive, mis-directed immune system.

Editor: Well, that's highly interesting. We're planning to do a survey of our members later this year, and it occurs to me that one thing we should attempt to find out is something about our people's family history of illnesses, including autoimmune illnesses.

Dr. Callegari: I think that is a great idea as it might suggest there was some priming or predisposition that took place.

Editor: Look at myself as an example, if you will. My mother had diabetes and my grandmother died of it. One brother developed rheumatoid arthritis at age 40. So I feel there is some basis there for a family history of autoimmunity.

Dr. Callegari: Yes, I think it's a great series of questions because I think much of the early questioning with focus on scleroderma and that family of diseases, as opposed to just general autoimmunity, like autoimmune thyroid disease - I mean sometimes people just don't recognize that the illness is really autoimmune in nature.

Editor: I was diagnosed with scleroderma before we knew it was EMS and still have many of the scleroderma manifestations.

Dr. Callegari: As many of the EMS people do, as you know. And there's another example of an illness that we define as autoimmune. Yet, EMS can mimic some aspects of it, and toxic oil syndrome mimics it in some aspects. Also, exposure to toxins may be involved. I mean, the rate of lupus is increasing in our population right now. Scleroderma is a little hard to tell, but I think the rate is going up. The rate's increasing, so we have an increasing amount of autoimmunity. So if you want to make an argument, and I think lupus lends itself best to it, is that, if there is a chemical, for instance, a pill, that can provoke lupus, why couldn't there be an environmental chemical that does the same thing? And in a sense here is an environmental toxin that triggered an immune response - EMS. Or like toxic oil. A contaminant triggered the whole host of autoimmune injury. It may be that you need to have a little bit of pre-programming, and you have to be in the wrong place at the wrong time; sometimes this is called a double-hit hypothesis.

Editor: Okay, you've mentioned the toxic oil syndrome. How are we doing after 9 to 10 years as compared to how those people were doing after 9 to 10 years? Are we doing about the same or what?

Dr. Callegari: I think in a sense there's some similarity. I think that group has not been studied as well long-term as EMS is going to be. I think that what happened was that much of the acute injury took place, and then people either gradually deteriorated from the initial injury or else, whatever new illness evolved, began to progress. So the people who developed scleroderma-like problems continued to have changes. I mean, it's like once the immune system gets provoked to look at things a little bit differently by the toxin, it always looks at things a little bit differently and causes more problems. I think one of the problems with EMS is that it's hard to look at everyone as a single group. It's very heterogeneous in terms of how the responses are. Some people have been left with clear-cut progressive neurologic injury, and some have been left with relatively "minor" (I use that term in quotations) problems. I think that's why it's hard to look at it as a group because it really isn't a group. It's really a collection of significantly-affected or moderately-affected, etc., persons. It breaks down into a number of different categories. To get back to the question: How are our people doing over time? I think what we're struck with is that any time you're left with an illness that can affect a number of organs, that it now becomes the contact for some of the other changes or illnesses that we are all susceptible to. So, on the one hand, having a chronic disease makes our outcome in other unrelated areas worse. But there is still some evidence in EMS of ongoing injury or certainly an ongoing effect. We can measure the blood and see that there aren't any new eosinophils present, but we can't assess ongoing injury effectively by simple lab testing. But what we've done is a quantitation of persistent or worsening symptoms: peripheral neuropathy, skin rashes, and sicca complex, (Sjogren's syndrome). We see these findings as the disease evolves, and it's likely related to the EMS. It's unclear what the mechanism is. I think all EMS people compared to the toxic oil people are probably doing a little less well because the toxic oil had less horrible systemic features than the EMS people had. They were more focal and scleroderma-like, but there hasn't been great follow-up in the interval since the toxic oil. It takes a lot of money to follow it.

Editor: So, if you look at your own patients and compare them to how they were doing a year or two ago, are they doing the same, worse, better, or what?

Dr. Callegari: Some of them are worse, some maybe the same, some have maybe some improvement in some areas.

Editor: Talk about the ones who are getting worse. How are they getting worse? Is it secondary diseases or fatigue or less mobility or what?

Dr. Callegari: A combination. I think some of it is secondary diseases evolving, ranging anywhere from fibromyalgia to diabetes or things like that. Some are getting worse because they've had a change - almost like a momentum that's taken place. For instance, a few who have peripheral neuropathy have had a progression of their peripheral neuropathy.

Editor: Dr. Callegari, what happens when that happens - I mean, how do you know that's happening to you?

Dr. Callegari: Most of the peripheral neuropathy that's been described, as you know, is sort of neuromuscular. Most peripheral neuropathies are stocking glove. There's an altered sensation in the distribution of the stocking or sock or glove. And one of the ways of seeing if things are progressing, is not so much seeing if there is a change in the way they feel, but rather, if the stocking is elongating, coming up the leg, or the glove is coming up the arm, so that there are more areas of altered sensation.

Editor: When you say "altered sensation" do you mean pins and needles and burning and similar sensations? So many of us with EMS complain of such things.

Dr. Callegari: Right. Pins and needles, burning, numbness, really altered sensations from the nerves that are involved. As more nerves become affected, the area of altered sensations begins to increase, and that is what we mean by progression. So the way to see it clinically is this: What may have started as altered sensations around the ankles or the foot, now affects the leg to mid-calf or can come up to the knee.

Editor: This may explain why some people may have now had to move to a wheelchair some of the time.

Dr. Callegari: Right, if the nerve injury progresses to the point where it becomes intensely painful, or you have trouble locating the position of your feet, that's a real problem.

Editor: What about pulmonary and cardiac problems? Are you seeing any increase in those?

Dr. Callegari: No, much of mine are neuromuscular patients, so I really haven't seen changes in pulmonary and cardiac. I mean, cardiac is a significant problem, and I know a number of people have died of heart-related problems, but I have not run into that in my practice.

Editor: Have you lost any of your patients?

Dr. Callegari: I've actually been pretty fortunate. No, I haven't in the group of people that I've been following, but I do know one of my former colleagues has lost a number of patients.

Editor: Well, would you say, then, from your knowledge of EMS, that most of the deaths have been connected to respiratory and cardiac disease and complications of those?

Dr. Callegari: Yes, I think it's true, though my understanding is that many of the deaths that have been reported have really involved neuromuscular-related injury. When I think of pulmonary, I think of direct lung involvement. Now, there are peripheral nerves, and then there are other nerves. But I don't really want to alarm people with peripheral neuropathy to have them become concerned that they're going to lose nerves to their breathing muscle. I think some of the people who've had deaths related to respiratory problems, if they have not been deaths related to pneumonias or problems like that, were people with rapidly advancing, aggressive neurologic injury, who had respiratory arrest because the nerves stopped making the muscles work. So I don't want to put a link there because peripheral neuropathy is a sensory-related problem - sensory nerves, not nerves that control muscles. No, but I've been unaware of lung-related problems like other scleroderma cousins, like pulmonary hypertension, and I don't think that's been prominent.

Editor: We had a death within the past several months due to bronchial pneumonia, for instance. And there have been other deaths due to various types of pneumonia. EMS patients seem to be susceptible to contracting pneumonia.

Dr. Callegari: Yes, they may be more susceptible. Any time you have an underlying chronic disease, any time you're less physically active - and well, not as often as before - but still, if people are on immuno-modulating medicines such as prednisone and methotrexate, these sometimes can lead to increased infection susceptibility.

Editor: Dr. Callegari, what are some of the tests that people with EMS should not go without and how often should they have them on average?

Dr. Callegari: For us, we look at CBCs and liver function tests, and it falls into a pattern of a series of tests called a chemistry battery. We follow those at about a 4 to 6 month interval in people relatively stable. If they're on concurrent medications, we actually increase the frequency, depending on the medicines, to as often as every two months, if they're medicines that can affect the liver or cause problems. The usual monitoring is somewhere around 3 to 4 times a year unless there is a significant amount of concurrent medicine which carries a toxicity associated with it.

Editor: Such as antidepressants?

Dr. Callegari: Right, the antidepressants, or the anti-inflammatory medications, the muscle relaxants. Those medications can irritate the liver so it's important to have some degree of surveillance. Often people with EMS have other concurrent medical problems and need laboratory monitoring for other things as well. And many of the people who take supplements that we've alluded to need to have liver function tests because it's unclear what's happening with those supplements. I actually think people who take outside supplements need to be more aggressively laboratory- monitored than people who are on drugs with known toxicities.

Editor: Any other tests? For instance, do you think it would be wise for EMS patients to have a yearly echocardiogram?

Dr. Callegari: Probably not. That's probably an unnecessary test unless there is cause, a reason. For instance, do people need to have serial EMGs? I don't know if you've ever had one, but they're uncomfortable and painful, although they can give us valuable information about nerve functioning. We only recommend repeat EMGs if there is a change in the physical exam suggesting a worsening of the neuropathy.

Editor: So blood tests are the main thing.

Dr. Callegari: And I would give a yearly cardiogram as well to make sure because there have been cardiac abnormalities and conduction abnormalities associated with EMS early on.

Editor: You've mentioned liver function tests already, so it does seem that this is an area you are rather careful to monitor with patients.

Dr. Callegari: It is because the liver is the final detoxification or recycling plant for any medicines we take. Virtually all of our medicines get broken down by the liver. So that is the reason they concentrate there, and they can cause injury there.

Editor: Is there any relationship between liver function and high cholesterol readings?

Dr. Callegari: Yes, it can be. People who have very high cholesterol can deposit fat in the liver, and that can cause liver function abnormalities. That's one of the common pathways.

Editor: We have an online EMS support group of about 60 people, and more than a few have said they have elevated cholesterol, myself included. I know some who are thin and eat 1,000 or fewer calories daily, yet their cholesterol might be as high as 260. Do you think that EMS, combined with a family predisposition towards higher readings, might cause this?

Dr. Callegari: It's interesting. I think cholesterol actually gets re-packaged in the liver. Perhaps another way of looking at it is that people who have genetically high cholesterol may be more susceptible to L-tryptophan-related toxicity. I mean, you can offer a lot of potential explanations, including the idea that the real problem is that you are genetically predisposed towards having elevated cholesterol. If you get exposed to L-tryptophan - well, that may worsen your underlying problem. Cholesterol problems like that in people who have very little dietary intake is really a hereditary-related phenomenon. There may be other explanations for the elevated cholesterol levels that you noted. People with EMS are often not as (aerobically) physically active, and aerobic activity is one thing that can help to lower cholesterol. Plus, the pain and arthritis-like problems that EMS people often have can lead to less activity. Less activity can lead to weight gain, which also raises cholesterol levels. The fatigue can often lead to problems with food preparation. There are higher fats and cholesterol in ready-prepared food.

Editor: I had surgery a few years ago, and that meant a long recovery. Pain has definitely kept me from being active.

Dr. Callegari: That is a very typical problem. It's very difficult to be physically active when you hurt so much. So what might be a borderline cholesterol gets a little bit more elevated in people who are more sedentary. I don't have a good explanation as to why elevated cholesterol may be more common.

Editor: Well, we should say we don't know for a fact that elevated cholesterol is more common among those with EMS. It's a perception I have from listening to people talk about starving themselves on low-calorie diets.

Dr. Callegari: But you know, diet only accounts for some of it. There are people who have low cholesterol despite eating "everything" and people who have high cholesterol despite eating "nothing."

Editor: Let's talk about dental problems. Are you noticing increased dental disease?

Dr. Callegari: There really are more problems, and I think they are related to dry eye- and dry mouth-related problems.

Editor: And that's part of the autoimmune process, too?

Dr. Callegari: Right, I think the prototype illness like that is Sjogren's syndrome where people have inflammation and irritation or injury to the saliva glands. We speak of saliva as a lubricant, but it actually has anti-bacterial properties and is a sort of defense to protect our teeth from cavities and bacteria in the mouth. As such, saliva helps to nourish and keep the gumline protected, so people become much more susceptible to decay when they don't make much saliva. And what makes it worse is that a number of the medicines we use for pain also decrease the amount of saliva. So, even if you start off not making much saliva, you can make even less.

Editor: Let's go on to esophageal problems such as acid reflux. I'm hearing from more and more who have this. I'm wondering how much is related to damage from our disease, or to pain medications used, or to dry mouth, or what?

Dr. Callegari: Well, I think it's a little bit of a combination. As you know, people with EMS are sort of in that scleroderma family of illnesses. Esophageal dysfunction can play a role where the actual nerve control of the swallowing mechanisms can be somewhat affected.

Editor: Sometimes I notice trouble swallowing, and sometimes it's okay.

Dr. Callegari: Right, right. That kind of intermittent swallowing dysfunction is a very common complaint of people with scleroderma or CREST. I think that at least some of it may be related to EMS's impact on the esophagus and the swallowing, and some of it can be heightened by various types of pain medicines. Sometimes anti-inflammatories can cause problems; sometimes narcotic pain medicines may cause more problems with reflux. I think it's an inherent injury site for people with EMS, but I think there are enough modifiers that can make it even worse and account for a higher frequency than you might anticipate.

Editor: Let's move on to the dreary subject of cancer. Have you seen cancer developing in your patients?

Dr. Callegari: I've been fortunate that I haven't.

Editor: Should people with EMS be concerned we may develop lymphoma or blood cancers down the road?

Dr. Callegari: I think it's a good idea for people to make sure that they're watched and under the care of a physician, and this means a thorough, regular physician examination on a regular basis. I think that sometimes because of illnesses like EMS, people tend to attribute everything to it, so we have to re-emphasize that with illnesses like EMS, our doctors need to recognize that even though EMS is a dominant force in people's lives, you don't want to miss something.

Editor: Do you see a lot of cognitive problems in patients?

Dr. Callegari: I do. It's actually one of the most prominent complaints that people have.

Editor: Is it getting a little worse or what?

Dr. Callegari: It's hard for me to say because I think sometimes people adapt to it. It's still a major problem, I think often the most significant problem, although people don't often complain as much about it as something that causes pain. Almost everyone when they're depressed has some suggestion that they're having a hard time focusing or something similar to that.

Editor: Can we basically say that EMS breaks down into categories of neuromuscular disease, neurocognitive disease, and pulmonary/cardiac disease? And does one or the other tend to predominate in individual patients, or do you see overlapping?

Dr. Callegari: I think you see overlapping, but they can be more predominant. I mean, I think neuromuscular is the most common symptom I see, either neuropathies, weakness, or cognitive function. If you want, you can sort of lump those together as neuro and muscular, and cognition gets in there. I think there are variations of this theme and that some people are fortunate to have only one significant organ problem while other people are unfortunate enough to have multiple, multiple problems.

Editor: Well, what do you do with your patients who have cognitive problems?

Dr. Callegari: We try to make sure there isn't any structural reason for it, such as repeated strokes. We look to see there are no structural reasons for it, and then we try to assess whether the deficits are from an associated depression. I often have people evaluated by a neurologist with a specialty in cognition in order to get a sense about whether I'm missing something. There are some laboratory tests you can look at such as thyroid, B-12, things like that, which are things you don't want to miss. Also, I think we need to look at depression because that's not a surprising thing to find to me. When people have chronic disease, it would seem to me to be amazing if they weren't depressed.

Editor: When you are talking to your patients who turn out to have cognitive problems, are you able to tell they have problems just by talking to them, or do you have to rely upon tests, or do they tell you they have problems?

Dr. Callegari: Well, some tell, and then usually, we just have to ask a bit. "Do you notice you're forgetting things?" "Do you have a problem finding words?" "Are you having trouble balancing a checkbook?" And then sometimes, it's important to have the family come in. I know it's going to sound strange, but often people may not have as much insight as others do because they don't think about it. But family members often volunteer information such as, "She was terribly distracted."

Editor: You could compare it to people with hearing problems. Sometimes they will deny the problem, but their families say, "You need a hearing aid."

Dr. Callegari: Right! Exactly! You know, we often have families do that. They come in and say, "My wife has been much more forgetful. She's not herself." So, you don't want to violate someone's privacy by going in and saying, "Look, I want to talk to your family about this." But if a family member comes in - or I often just say, "Can you ask your family?" "Has anyone in your family commented or noticed?" And that begins to be an open forum for where to go next. I think it's important: Every chronic disease has depression associated with it. The numbers are about 20 to 30% of people with chronic disease become depressed. Certainly, in my fields I'm most responsible for - rheumatoid arthritis, lupus, fibromyalgia - it doesn't matter which one. About a third of people become depressed. So, depression is such a common problem, but again, you want to make sure that you don't default to it. I mean, you want to make sure that you don't say the person is just depressed. You have to really look past that. Otherwise, you tend to generalize. And in the five-minute doctor visit, you know - "How's your blood pressure?" "How are you doing?" "Oh, okay, you can get down now, okay." You know. (chuckling)

Editor: Yes, and sometimes patients don't like to be "bad" patients, so they fail to inform their doctors of their complaints. I think that doctors sometimes need to be a little more aggressive in questioning some of their patients. Well, let's go quickly through several things. How many of your EMS patients have trouble sleeping still?

Dr. Callegari: Oh, I think the majority of them have problems sleeping, primarily because of pain.

Editor: OK. How many of them still have severe pain?

Dr. Callegari: Some require daily narcotic medications to control their pain.

Editor: What about fasciitis? Is that still a problem for your patients?

Dr. Callegari: Had it before or have it now? I mean, a lot of people had it initially, but it's not as active. It's improved.

Editor: What about atrophy of muscles?

Dr. Callegari: That is still a problem, but that's also made worse by pain and disuse.

Editor: Now, let's look at fibromyalgia. Would you say that most of your patients do have fibromyalgia?

Dr. Callegari: I think some do, many do. I think "most" may be stretching it a bit.

Editor: Is there anything different about fibromyalgia pain and EMS pain? You've seen both kinds of patients.

Dr. Callegari: Right. It's a hard one to answer. I mean, pain is so subjective, that it's hard to say. I think both pains tend to be less responsive to narcotic pain medicines, so in a sense there may be some similarities.

Editor: What are they responsive to?

Dr. Callegari: Well, it depends on the person. We might use combinations. Sometimes pain medications aren't very satisfying, and they don't work very well for some types of pain. I think in those circumstances we have to rely on pain adjuncts: medications, like the antidepressants can sometimes be used, or people can consider using drugs like Neurontin, an anti-seizure medicine, which can also be used to treat nerve-related pain. It becomes very individual in terms of exactly what you do next. I use anything we can within reason for some level of control and to address the problem. You want to make sure you don't make any mistakes by mistreating pain and ignoring pain.

Editor: Are a number of your patients still using prednisone?

Dr. Callegari: No. Right now, none of them are, but I'm fortunate.

Editor: Methotrexate?

Dr. Callegari: No, I also don't have anyone on methotrexate right now.

Editor: Should people still on prednisone try to get off it?

Dr. Callegari: I think that they should, just because of the long-term ramifications, but that's one of those things we want to treat diplomatically. We don't want to say it's a bad therapy if it's a needed therapy at the time. I mean, I don't want people to think, "Oh, my gosh, my doctor doesn't know anything because of this and that." And, I think, I put it under the umbrella, that as with all medicines that have significant potential toxicity, it's important to work with your doctor so far as the ongoing need for those medications. That might be a better way of putting it. It's important that everyone is on the same page as to why we're still taking the medicine.

Editor: What is your opinion of methadone for EMS pain?

Dr. Callegari: Well, methadone is a long-acting pain medicine, and it's a very good long-lasting pain medicine. I think that people with EMS often are left with incredible pain. I think that any of the narcotic pain medicines, including methadone, are very reasonable options for people with severe pain.

Editor: Do you have anything else to add on pain treatment?

Dr. Callegari: I think people are recognizing that we need new approaches to pain management. There are a number of new agents available as well. What we need to do is educate ourselves more about the pain needs of our patients rather than focusing on denying the pain exists.

Editor: Are most of your patients partially or entirely disabled?

Dr. Callegari: Yes, most of them are disabled. They couldn't work the career they worked before.

Editor: Just briefly, do you have anything you can say to people who are trying to get Social Security Disabilty in terms of how they can work with their doctors?

Dr. Callegari: It's just a very difficult area. It really depends a lot on the lawyer's level of understanding. I think most doctors will provide the kind of support needed, but patients should use attorneys who are experienced in handling social security disability cases, too. It's important that patients' lawyers and doctors be able to work well together.

Editor: Please talk about research. Can we have hope in that?

Dr. Callegari: Yes, there are a lot of reasons for hope. Aside from just general medicine, I think that agents like serotonin and Redux are all re-focusing attention on L-tryptophan serotonin pathways. I think we'll have a much better understanding about this pathway, and that can only help people with EMS to understand more about their disease. I think we're still in an era of reactive caution. We have to react to where this illness takes people. We need to deal with the problems of EMS as they evolve, but my hope is that we'll have a better understanding about this entire chemical pathway so we can avoid it for the future. And, hopefully, at the same time, we'll have a lot of ways in which we can try to control it.

Editor: Many of our people feel isolated and alone. Their doctors don't seem to understand their problems. I hear from some who are very despondent at times. Do you have any encouraging suggestions?

Dr. Callegari: One of the things that the EMS Network has done is to allow people not to feel as isolated about their illness. It's very easy when you have problems to feel that there is no hope, but I think people who feel hopeless, clearly need professional help in terms of trying to turn the tide. There are many illnesses which have devastating problems with them, and all of us at some point lose hope when faced with physical illness. I mean, let's give people hope. There are newer therapies being evolved to treat pain and other problems. We are now beginning to understand pain in a very different light. Before it was ignored, and now it's being addressed.

Editor: Dr. Callegari, thank you so much. You have been wonderful to talk to us today. Is there anything else you'd like to say?

Dr. Callegari: Even in the past 10 years where we've begun to describe the illness, we've made strides in terms of understanding. Sometimes I tell my patients with arthritis, "If we can hang in there and wait around long enough, we can find out more information and things that are going to have a real benefit to us." I think what is important is to stay in there with your EMS. Try to realize that we haven't reached the end, and people haven't abandoned research or the issues about this disease. I'll give you an example using rheumatoid arthritis. If you look back, medicines to treat it have not altered all that much over time. But in the next five years, we'll probably see many new ways to treat rheumatoid arthritis. So, the lesson is that, if you hang in there long enough, something is going to happen. Although people may feel as if they've had EMS forever, remember it's a new disease. As we have more time to think about it, we'll develop better ways to deal with EMS.

Copyright 1998 National EMS Network, Inc., and Peter E. Callegari, M.D.

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Each person should seek the medical advice of their own medical professional for their own situation. The information contained in this article is of a general nature.