By Paul M. Rowe
Editor’s note: Pro Health’s upcoming issue of the Healthwatch CFS & FM newsletter will feature an article by CFIDS patient Patti Schmidt, who was recently diagnosed – much to her surprise, as having chronic Lyme disease. In light of this information, the following article should be of interest to other CFS patients.
Mention of chronic Lyme disease raises temperatures, not only among patients, but also among the experts who are trying to untangle exactly what chronic Lyme disease is, why only some patients get chronic manifestations, and how the disease should be treated. Lyme borreliosis is a complicated disease in which both the specific disease-causing organism and host responses seem to affect the course of disease.
In Europe, Lyme borreliosis is caused by any one of the three tick-borne spirochetes in the Borrelia burgdorferi sensu lato complex–B burgdorferi sensu stricto, B afzelii, and B garinii. In the USA, only the first species is involved. Everywhere, the usual early sign is erythema migrans–a red bull’s-eye rash. Stage II Lyme disease–i.e., early dissemination–can involve the skin, joints, muscles, or the central and/or peripheral nervous system. In the USA, arthritis is the most common late-stage sign, but in Europe, radiculomyelitis, peripheral neuropathy, or chronic skin involvement (acrodermatitis chronica atrophicans) is seen more often.
Lyme disease is treated with a course of antibiotics, and although most patients will respond well, there is disagreement about how to treat late cases, particularly with respect to the duration of antibiotic treatment.
Chronic Lyme disease or post-Lyme-disease syndrome are terms for the clinical picture of patients who have chronic symptoms after what is thought to be adequate antibiotic therapy. The underlying mechanism of these symptoms is unknown, and the management of these patients is controversial. The answer hinges on whether the disease-causing organism is still present or whether these symptoms are a result of the host immune response against the organism or even against tissue autoantigens.
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The controversy is most intense in the USA. Roland Martin (National Institutes of Health, Bethesda, MD, USA)–a researcher from Germany–is “amazed at how different the US nervous-system manifestations look. In Europe, we assumed people would respond to treatment, with almost no exceptions. If there was permanent organ damage, it would not be completely cleared up, but at least it would not progress; but here, the signs are much more subtle, for example the cerebrospinal fluid inflammatory findings. Therefore, Lyme disease appears more complicated here than in Europe”.
The complex clinical picture is compounded by a history of inconsistent laboratory tests and the lack of a standardized diagnostic definition. Laboratory tests are improving all the time, but for now, the only standardized way to measure the incidence of Lyme disease is the US Centers for Disease Control and Prevention surveillance case definition. This, however, may miss some cases of Lyme disease. It also does not include chronic Lyme disease or post-Lyme-disease syndrome. Thus, says Leonard Sigal of the University of Medicine and Dentistry of New Jersey (New Brunswick, NJ, USA), “there is no way to know how common the chronic condition is. There are definitely people with Lyme arthritis who do not respond to antibiotic therapy. They have red, swollen, tender joints that just do not resolve”.
But there are patients with non-specific complaints and no objective findings who also do not respond to treatment. These patients, suggests Sigal, may not actually have Lyme disease, a viewpoint unpopular with patients who believe that doctors sometimes wrongly withhold antibiotics. Sigal insists that “there is no documented example of B burgdorferi that did not die when exposed to antimicrobials”, but he acknowledges that there is no way of knowing whether unreachable organisms can survive in a treated person. In an attempt to clear up this controversy, the US NIH are funding placebo-controlled trials of long-term antibiotic therapies for patients with chronic Lyme disease or post-Lyme-disease syndrome.
Meanwhile, Martin and his colleagues are pursuing the hypothesis that autoimmune responses to tissue antigens may play a role in these conditions. By studying T-cell clones from patients with chronic disease, they have identified several candidate autoantigens that could be involved in the neurological and musculoskeletal symptoms at several stages of the disease. “It has become clear that the deletion of autoreactive T cells in the thymus is incomplete”, says Martin. “We all carry autoreactive T cells for many autoantigens, and, under circumstances such as up-regulation of HLA molecules, co-stimulatory molecules, co-receptors, and adhesion molecules in an affected tissue, these cells may be triggered to cause organ damage.”
The idea that Lyme disease complications may have an autoimmune origin began with the finding that Borrelia-infected patients with the most severe and prolonged arthritis have large numbers of antibodies against outer surface protein A (OspA) of borrelia, and the subsequent discovery of a protein that resembles OspA on human cells. But experience with the Lyme disease vaccine (recombinant OspA) approved last year in the USA illustrates that, if autoimmunity is indeed involved, it must take more than the mere presence of a foreign protein that resembles a self-protein to trigger a pathological attack on self-antigens. The vaccine has passed all its safety tests, and the regulatory agencies (US Food and Drug Administration and US Centers for Disease Control and Prevention) have found no evidence of an association with arthritis.
So what does cause chronic Lyme disease? The question remains wide open. Sigal argues that “molecular mimicry has not been proven to be a significant issue in the genesis of Lyme arthritis; it may require seeding of the joint with bacteria”. And Dennis Parenti of SmithKline Beecham (Collegeville, PA, USA) notes that “although T-cell cross reactivity is common, it does not imply molecular-mimicry-mediated pathology or autoimmunity.” Even Martin admits that, “one cannot easily distinguish between organ damage that will not go back to normal, or persistence of the organism, or an ongoing immune response that was initiated by the organism. Some damage could be bystander damage from secretion of cytokines in vulnerable tissue and this damage can look like autoimmunity”.
More research is needed, conclude the scientists, to determine what is going on in chronic Lyme disease and how to treat it.
Source: The Lancet (www.thelancet.com) (04/22/00) Vol. 355, No. 9213, P. 1436.