Chronic EMS Autoimmune Study
By Kevin L. McKinley, M.D.
Dept. of Neurology/Neuromuscular Diseases
Ochsner Clinic, New Orleans, LA

As we move into the 8th year of the medical odyssey known as the Eosinophilia-Myalgia Syndrome, I certainly hope that the medical community is able to reach an agreement as to the most likely cause of continued symptoms in patients who suffer from EMS, to put it simply: "What Causes Chronic EMS." More likely than not, there will be more than one reason for continued symptoms. In one patient we may find one reason and in another patient we may find another. I personally feel that a significant number of patients with continued symptoms related to EMS suffer from a chronic autoimmune condition. In other words, many patients have an overactive immune system which is causing continued symptoms of fatigue, muscle pain, and memory dysfunction.

From the start I would like to say that my opinions are not necessarily those of the majority of EMS experts. Unfortunately, I do not feel that my colleagues have offered any reasonable explanation for chronic EMS (with a few rare exceptions that involve some high-tech research that has revealed some unusual findings that are not readily explainable, such as altered tissue magnesium and ATP levels.)

Early in the study of EMS I split with my colleagues because I felt it was unethical to accept research funding from Showa Denko K.K. I personally did not feel that I could evaluate the EMS epidemic in the proper fashion if I were influenced financially and emotionally by Showa Denko K.K. I mention this as one reason why my personal theory regarding the immune mechanisms of chronic EMS has not gained more widespread acceptance within the medical field. There are multiple other reasons why my theory has not been accepted but, perhaps most importantly, I may just be wrong.

My theory is that many patients with chronic fatigue, muscle pain and memory problems following EMS have an overactive immune system. Your immune system is a very complex thing which contains cells such as neutrophils, eosinophils, lymphocytes, and macrophages. It contains proteins such as complement and immunoglobulins, and it involves a number of complex chemical signals that help coordinate the whole system, including cytokines and interferons.

In a number of medical conditions like lupus, multiple sclerosis, rheumatoid arthritis, and EMS, the immune system is known to be overactive. In EMS during the early stages of the illness, we found evidence of the abnormal immune system response on multiple blood tests and in tissue samples from a variety of organs. In the early stages (the first six months of EMS), the degree of immune system overactivity was incredible. An absolute five-alarm "immune" fire raged throughout the tissues of many patients who suffered from EMS. I was one of the first pathologists to describe the microscopic findings in the nerve, muscle and fascia of patients with EMS.

The immune system was dissolving the tissue and choking off the blood supply. These findings weren't mild. This was a true five-alarm fire. I personally believe in many patients a smoldering "immune" fire has continued and is responsible for many complaints.

One of the main reasons I hold this belief is based upon the results of research that I performed at the Baylor College of Medicine in Houston, Texas. We followed seven patients with EMS into the late stages of their illness. During this time we used a blood test known as the soluble interleukin-2 receptor to monitor the level of overactive immune response. When some components of the immune system are overactive, the blood level of this test rises. In five of our seven patients, symptoms of chronic EMS developed, and in these same five patients this blood test remained abnormally high.

Interestingly, when patients improved from specific treatments such as plasmapheresis (a blood cleansing procedure) or Prednisone, the blood test values also significantly improved. This correlation between symptoms and this blood test abnormality suggested that there was a link between the immune system activity and the chronic fatigue, muscle pain, and cognitive dysfunction our patients suffered. Our results are published in the journal, Muscle and Nerve, September 1993, pages 947-951. Unfortunately, this was a very small study, and the results of this study did not meet with an enthusiastic response from the EMS community of physicians.

A group of researchers in Spain took interest in our paper and performed the same blood test on 12 patients suffering from chronic symptoms from the Toxic Oil Syndrome, the medical illness that most closely resembles EMS and was triggered by ingestion of contaminated cooking oil in Spain in 1981. Of the 12 patients with chronic TOS symptoms of muscle cramps and pain, eight had elevated levels of the soluble interleukin-2 receptor. Their results are published in Muscle and Nerve, October 1994, page 1228. Based on this information it seems likely that the immune system has remained overactive in two-thirds of patients with chronic symptoms of TOS, an illness that is almost identical to EMS. If this holds true for EMS, doctors will be able to try treatments, monitor your blood tests and symptoms for signs of improvement, and hopefully help you feel better.

So where do we start? Unfortunately, patients with EMS are rather rare. For argument's sake, let's say there are 1,000 patients with chronic symptoms of EMS spread across the United States. This would mean that it would take a city of 1,000,000 to find four patients with EMS in one place. This makes it very tough on doctors to do any sort of research. It may be necessary for members of the EMS support groups to become involved in their own health care if we want to answer some of the questions that could lead us to successful treatments for the chronic symptoms of EMS. We need several key things to get even the simplest questions answered.

First, we need 30 to 50 people that had definite CDC-defined EMS (severe myalgia, eosinophils of over 1000, no other illness to explain the problem). Ideally, all would have onset of symptoms between 1989 and 1990. Furthermore, all would have received a diagnosis of EMS from a respected expert in EMS or a board-certified rheumatologist.

This group would currently suffer from chronic severe myalgia and fatigue. Most importantly, this group did not have myalgia, fatigue, or fibromyalgia prior to EMS. This group would need to have some lab testing to look for chronic immune abnormalities and would need to have a local doctor willing to cooperate with ordering tests and giving the patient the results. The local doctor will also serve to ensure that only eligible patients are included in the study and to protect confidentiality. Anyone considering participation in this project needs to discuss all aspects of this article with their local doctor and allow him/her to help decide if you would be a good patient for this study.

The results would need to go to a central location for analysis. It would be ideal for the patients to rank their symptoms of fatigue, myalgia, cramps, numbness, and memory problems on a 0 to 10 scale, with 0 being no problem and 10 being the worst problem imaginable. They should also list the number of "good hours" they have in a day and the number of "good days" in a week. I would also like them to list degree of total disability they suffer from 0 to 100%.

The tests I feel would be most helpful are the ESR, CRP, RA, and soluble interleukin-2 receptor. The first three tests are routine and could be done at any lab, but the last one is used to monitor transplant patients' immune functions and is only available at large centers and, in my experience, is the most important of the tests.

There are a number of additional blood tests that may also be useful but can be rather expensive and are sent by mail to reference laboratories. An easy way to get a large panel of tests is to have your doctor order the immunoserological panel from Immunosciences Lab, Inc. (Beverly Hills, CA; (310) 657-1077) which includes 35 tests that look at many aspects of the immune system.

In order to assure confidentiality, each participant in the study may wish to photocopy their lab results and then cut their name off or cover it with white-out. They should mail the nameless data, along with their physician's signed sheet, to the central collection center. To make sure the data does not get confused, all three sheets should be identified by your date of birth.

If the EMS Support Group is able to coordinate an effort such as this, and 30 to 50 patients are able to rank their disease severity and get the above testing, the medical community would gain some important insight into chronic EMS. If I'm right, we may be able to effectively treat the chronic fatigue, myalgia, and other problems so many of you suffer.

If I'm wrong and these tests don't provide helpful information, there are several other potentially treatable causes of chronic symptoms. Many EMS doctors feel that chronic EMS symptoms are either due to depression or fibromyalgia, and both of these illnesses may respond to treatment. Some experts feel the chronic symptoms are motivated by lawsuits and hopefully everyone will be better once the lawsuits are over. Some experts deny there ever was EMS, and say this whole thing is one big mix-up. There are several other ideas other doctors have expressed.

I hope you will look at the above list and see if you may explain a lot of your current problems because of depression, fibromyalgia, legal issues, or other medical problems. If so, please exclude yourself from this project (if it gets going). If the results of this project are impressive, it may be possible to next sort out patients who have both significant contributing illness (depression, fibromyalgia, others) and immune overactivity. But for now, I hope that we can study a rather small number of EMS patients that are affected by chronic EMS without a history of significant depression or fibromyalgia.

A project like this takes a lot of work. I wish to congratulate anyone who has read this and is now saying, "Yes. I'll do my best to honestly report my symptoms and their severity, and I'll ask my doctor about checking some lab tests." Hopefully, we can designate someone to collect and organize the results, and next year you'll turn on your computer or open your EMS newsletter and get to read the results.

(C) Copyright 1997 Kevin L. McKinley, M.D.

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