tick-borne Infections

Why is chronic Lyme disease chronic?

Several factors may account for persistent symptoms. These include low grade persistent infection which either causes damage directly or indirectly through the inflammatory and toxic effects of an activated immune response, permanent damage as may occur in brain injured patients, or a Lyme-triggered autoimmune reaction.

The persistent infection hypothesis is based on several lines of evidence. Clinical case reports and large clinical series indicate that some patients benefit from longer and repeated courses of antibiotic therapy. Published reports indicate that, even after antibiotic therapy, persistence of the spirochete Borrelia burgdorferi may be demonstrated by either culture or demonstration of Bb DNA by PCR analysis in animals and humans. The mechanisms of persistence and immune evasion are thought to include sequestration in intracellular or other immunologically privileged sites, antigenic variation, decreased expression of surface antigens in vivo, capture of the host-cell’s own membrane forming a virtual immunoprotective cloak, and/or early down-regulation of the immune response. Much evidence now exists to demonstrate that Bb can lodge intracellularly in human endothelial cells, astrocytes, fibroblasts, and macrophages. Bb in vitro has been shown to enter B Lymphocytes and to exit drawing with it the outer surface membrane of the lymphocyte. Bb in vitro can modify its shape into potentially antibiotically-protected cyst-like forms. These findings suggest that failure to eradicate Bb completely by antibiotic therapy may be due to intracellular localization in vivo, the selection of resistant strains, or sequestration in sites (such as the central nervous system) where antibiotic penetration may be less adequate.

The post-infectious inflammatory hypothesis also is supported by several lines of evidence. For example, patients with Lyme arthritis who carry the HLA-DR4 or DR2 allele are more vulnerable to developing a chronic antibiotic-resistant arthritis. Indirect evidence exists to support molecular mimicry as at least one possible explanation for persistent symptoms. For example, the flagellin protein (on the tail of the spirochete) can generate antibodies that cross-react with myelin basic protein, thereby contributing to axonal dysfunction. Finally, remnants of pieces of the spirochete may result in a persistent activation of the immune system, causing the production of interleukin-6, tumor necrosis factor, and nitric oxide. These cytokines produce fatigue and malaise, two of the more prominent symptoms experienced by patients with chronic Lyme disease.

It is reasonable to assume that some patients suffer from persistent infection whereas others suffer from immune-mediated post-infectious damage. Until more is known about the factors which identify who may respond to repeated treatment and who is unlikely to respond, clinical decisions will be based on physician preference rather than objective data. Longer vs shorter duration placebo-controlled antibiotic trials need to be conducted with long-term blinded follow-up using objective markers. Until then, the optimal treatment of the patient with chronic Lyme Disease will be unknown. At this point in medical history, decisions about the treatment of the patient with chronic Lyme disease need to be individually shaped by the clinician’s experience, the patient’s clinical profile and history of antibiotic responsiveness, and the emerging medical literature.

Patients with chronic neuropsychiatric Lyme Disease may benefit from adjunctive therapies that provide symptom relief. For example, patients with an increased sensitivity to noise may benefit from gabapentin (Neurontin) or carbamazepine (Tegretol) treatment. The latter medicine may also be helpful to reduce skin hypersensitivity or headaches. Patients with marked distractibility and inattention may benefit from medicines used to treat Attention Deficit Disorder, such as bupropion (Wellbutrin) or methylphenidate (Ritalin). Patients with prominent fatigue may benefit from the latter medications as well.

Consultation with a Lyme literate psychiatrist can be very helpful both to address the psychological impact of a chronic illness as well as to address the psychiatric symptoms that may have been triggered. Psychiatric medications such as sertraline (Zoloft), fluoxetine (Prozac), paroxetine (Paxil), fluvoxamine (Luvox), and citalopram (Celexa) may be helpful for patients with depressed mood or irritability. Medicines, such as the anti-convulsants (gabapentin, valproate, carbamazepine), are also very good mood-stabilizers and may serve to help patients with marked mood shifts, neuropathic pain, and/or sensory hyperacuities. Other medicines, such as amitriptyline (Elavil) or nefazadone (Serzone), may be very helpful for sleep and for reducing pain.

Consultation with a neuropsychologist with expertise in cognitive remediation can also be helpful. Cognitive remediation refers to the retraining of the brain to accomplish tasks that were previously done automatically. Cognitive strengths are used to compensate for current weaknesses. Such approaches have been developed for patients with persistent cognitive deficits after head injury, for example. Similar strategies may be helpful for patients with persistent Lyme Disease. The best places to find experienced remediation therapists would be Centers for Brain Injury Rehabilitation.

Ongoing attention to the problem of “deconditioning” needs to be addressed. Because patients with chronic Lyme Disease often experience dramatic fatigue (much akin to patients with Chronic Fatigue Syndrome), they spend much time in bed and so their muscles lose tone over time. This can lead to an ever worsening syndrome in which patients get tired after exercise and so avoid it. Further deconditioning results such that even less exercise the next time leads to considerable post-exertional fatigue. To counter this cycle, a very gradual but progressive exercise regimen needs to become a daily part of the patient’s routine for a maximal return to health.

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