KROONINEN BORRELIOOSI JA SEN HOITO

[Bb]

Lähettäjä: Soijuv Lähetetty: 25.4.2004 18:41

Tässä on Dontan artikkeli vuodelta 2001. Donta kirjoitti minulle tänään ja antoi mm. luvan käyttää artikkeleitaan sivuillamme - hyvä juttu. Tässä artikkelissa hän puhuu mm. IgM vasta-aineen jatkuvasta positiivisuudesta kroonisessa borrelioosissa sekä ehdottaa antibiooteiksi tetrasykliinejä ja makrolidejä yms. Krooninen borrelioosi on hänen mukaansa tosiasia eikä spekuloinnin aihe.


The Existence of Chronic Lyme Disease

Current Treatment Options in Infectious Diseases 2001, 3:261?262

Current Science Inc. ISSN 1523?3820

Copyright © 2001 by Current Science Inc.

Sam T. Donta, MD

Address

Infectious Diseases, Biomolecular

Medicine, Lyme Disease Unit, Boston

University and Boston Veterans Affairs

Medical Centers, 650 Albany Street,

Boston, MA 02215, USA.

E-mail: sadonta@bmc.org

Patients who become infected with Borrelia burgdorferi may have acute signs of infection, be asymptomatic, or develop manifestations of the disease.

Some of the common consequences of infection include neurologic signs and symptoms such as headache, meningitis, and Bell?s palsy; musculoskeletal involvement in the form of myalgias and arthralgias, with or without arthritis; fatigue; and a chronic multisymptom disorder.

Whereas certain manifestations of Lyme disease are relatively easy to recognize, such as erythema migrans, Bell?s palsy, bradycardia with heart block, and arthritis (especially monoarticular or oligoarticular), recognizing the chronic multisymptom form of the disease has created more difficulties.

Chronic Lyme disease is indistinguishable from other multisymptom disorders that are termed chronic fatigue, fibromyalgia, multiple chemical sensitivity, and Gulf War illness. These are terms that describe the principal symptoms or epidemiologic association, but not the underlying cause. All these disorders share the major triad of symptoms: fatigue, muscle/joint pains or stiffness, and neurocognitive or neuropsychiatric dysfunction. There are additional symptoms, probably neurologically related, such as paresthesia, tremor, palpitation, dysequilibrium, gastrointestinal disturbances, and urinary frequency. Lyme disease is a common cause of fibromyalgia and chronic fatigue, especially in endemic areas, and should serve as a model for other potential causes of chronic fatigue and fibromyalgia. The epidemiologic studies of Shadick et al. [1], Asch et al. [2], and our institute [3?6] have established that well-documented cases of Lyme disease, including those in patients with known tick bites and typical rashes, may progress to the chronic multisymptom form of this disease, even if treated.

There have been attempts to distinguish late Lyme disease from chronic Lyme disease, or to deny the existence of chronic disease, claiming that the various symptoms are part of daily life [7]. Late disease has been said to be that of limited involvement of the joints (in the form of an oligoarticular arthritis) or the neurologic system (in the form of meningitis, Bell?s palsy, radiculopathy, or encephalopathy). In addition, diagnosis and treatment of late disease is relatively easy and straightforward. This appears to be the case in many patients who have prominent serologic responses, especially IgG, to many of the antigens of B. burgdorferi, and who appear to respond well to limited courses of antibiotics.

In contrast, chronic disease appears to generate less robust immunologic responses and requires longer courses of antibiotics to control or cure the illness [3?6]. Typical of most cases of chronic disease, there are IgM responses with limited IgG responses. The IgM responses to highly specific proteins of B. burgdorferi, such as 23kd (OspC), 31 kd (OspA), 34 kd (OspB), 35 kd, 37 kd, 39 kd, and 83/93 kd, and the most commonly seen response to the 41-kd flagellar protein, indicate infection by B. burgdorferi and are frequently signs of disease activity. The IgM reactivity is not unique to chronic Lyme disease; there are examples of other infections that retain IgM reactivity concurrent with active disease (eg, hepatitis B) or express reactivation of disease (eg, toxoplasmosis, cytomegalovirus).

With successful treatment, the IgM responses in chronic Lyme disease dissipate, sometimes with seroconversion to IgG reactivity [3].The mechanisms underlying the persistent IgM reactivity and limited IgG reactivity need to be determined but may involve a failure to switch from IgM to IgG responses. Treatment of the chronic disease has not been optimized, but much has been learned through trial and error. Symptom-oriented treatments such as amitryptilline, exercise therapies, and anti-inflammatory agents appear to be of limited value, similar to outcomes seen in chronic fatigue and fibromyalgia. The best treatmentsthus far appear to be antibiotics capable of intracellularpenetration, such as the tetracyclines and the macrolides. With the tetracyclines, the parent compound appears to be much more effective than doxycycline or minocycline, possibly because of the higher dose and less proteinbinding for tetracyline. The limited clinical activity of macrolide antibiotics, despite excellent in vitro sensitivities and intracellular penetration, appears to be greatly enhanced with the concomitant use of lysosomotropic agents (especially hydroxychloroquine) that alkalinize intracellular acidic endosomes [8]. The concomitant use presumably enhances macrolide antibiotic activity, which is otherwise limited at an acid pH [4]. These clinicalobservations also support the hypothesis that the borreliapersist intracellularly in an acidic environment. With tetracycline or augmented macrolide therapies, the duration of therapy appears to be an important determinant of outcome. If chronic disease is present for morethan 1 to 3 years, it appears that 12 to 18 months of treatment is needed to cure or control the disease, with longer duration of illness requiring longer courses of therapy. Some patients with long-term chronic disease appear to have limited or no response to treatment, the reasons for which are unknown. The need for long courses of treatment is not unique to Lyme disease. Other chronic infections such as tuberculosis, leprosy, some fungal infections, and Q fever may require months to years of antibiotic therapy for adequate resolution or control of the disease.

There are more questions than answers for chronic Lyme disease. The existence of the disease should no longer be a question because the results of animal studies support the existence of persisting or relapsing infection [9?11]. The key questions that need to be addressed involve the mechanisms underlying the disease, how best to diagnose and distinguish the disease from other chronic multisymptom disorders, and how best to manage and treat the disease.

References and Recommended Reading

1. Shadick NA, Phillips CB, Logigian EL, et al.:

The long-term clinical outcomes of Lyme disease.

Ann Intern Med 1994, 121:560?567.

2. Asch ES, Bujak DI, Weiss M, Peterson MG, Weinstein A:

Lyme disease: an infectious and postinfectious

syndrome. J Rheumatol 1994, 21:454?461.

3. Donta ST: Tetracycline therapy of chronic Lyme

disease. Clin Infect Dis 1997, 25:S52?S56.

4. Donta ST: Plaquenil improves the efficacy of

macrolide antibiotics in the treatment of Lyme

disease. VI International Conference on Lyme Borreliosis.

1994, Bologna, Italy. Abstract P056W.

5. Donta ST: Macrolide therapy of Lyme disease.

X International Conference on Neuroborreliosis, 1998,

New York, NY.

6. Donta ST: Treatment of chronic Lyme disease with

macrolide antibiotics. VIII International Conference

on Lyme Borreliosis, 1999. Munich, Germany.

Abstract P193.

7. Seltzer EG, Gerber MA, Cartter ML, Freudigman K,

Shapiro ED: Long-term outcomes of persons with

Lyme disease. JAMA 2000, 283:609?616.

8. Maurin M, Benoliel AM, Bongrand P, Raoult D:

Phagolysosomal alkalinization and the bactericidal

effect of antibiotics: the Coxiella burnetii paradigm.

J Infect Dis 1992, 166:1097?1102.

9. Straubinger RK: PCR-based quantification of Borrelia

burgdorferi organisms in canine tissues over a

500-day postinfection period. J Clin Microbiol 2000,

38:2191?2199.

10. Cadavid D, O?Neill T, Schaefer H, Pachner AR:

Localization of Borrelia burgdorferi in the nervous

system and other organs in a nonhuman primate

model of Lyme disease. Lab Invest 2000, 80:1043?1054.

11. Roberts ED, Bohm RP Jr, Lowrie RC Jr, et al.:

Pathogenesis of Lyme neuroborreliosis in the Rhesus

monkey: the early disseminated and chronic phases

of disease in the peripheral nervous system. J Infect Dis

1998, 178:722?732.