Prolonged antibiotic therapy in PCR confirmed persistent Lyme disease

Prolonged antibiotic therapy in PCR confirmed persistent Lyme disease

Wolfgang Klemann, MD, Leopoldstr. 17, 75172 Pforzheim, Germany, Phone: +49 (0)7231 313159, Fax + 49 ( 0)7231 106161, Email: w.klemann@dr-w-klemann.de

Bernt-Dieter Huismans, MD, Am Haldenberg 24, 74564 Crailsheim, Germany, Phone: +49 (0)7951 26 33 0, Email: BHuismans@t-online.de

Stephan Heyl, MD, Primelweg 13, 71229 Leonberg, Germany Email: stephan.heyl@googlemail.com

Abstract: We examined a sample of 90 individuals that had previously received a course of appropriate antibiotics for Lyme disease without experiencing full resolution of their symptoms and had evidence of persistent infection documented by PCR analysis.

Mean duration of symptoms was 9.5 years (range 1 - 40 years). The treatment was adapted to the individual case according to clinical response. Long term antibiotic therapy was initiated and patients were treated continuously for at least 6 months, in some cases several years of intermittent therapy was administered. About 38,8% of the patients experienced full remission of symptoms while about 56,7% reported a significant improvement, 5,6% of patients were deemed refractory to therapy. Therapeutic modalities are discussed in detail.

Key words: persistent Lyme disease, Borrelia PCR, long term antibiotic treatment, lyme serology, Borrelia DNA

Key issues:

- All study patients were Borrelia- DNA positive
- Commonly reported symptoms included fatigue, muscolo- sceletal and neuro-psychiatric complaints
- Only about 42% of patients had a history of an erythema migrans
- Serologic testing is fairly insensitive in late disseminated lyme disease
- Antibiotic treatment must be tailored to the individual clinical response in late disseminated lyme disease
- The majority of patients benefited from long term antibiotic treatment
- Recurrence of symptoms was common during treatment
- Long term antibiotic therapy was generally well tolerated

Introduction

Lyme disease was first described as an independent entity by Allen C. Steere et. al. [1] in 1977. Since then we have learned that this complex illness is the result of an infectious process, that not only affects the skin and joints but can potentially disseminate systemically. Although 30 years have passed since the discovery of the disease, the available data on therapy still has to be considered sparse. In a review article published in 2006 D. Hassler summarized the available data on the treatment of lyme disease and commented on the paucicity of evidence [2]. Only a few controlled studies and some in vitro observations are available. Nevertheless certain standards have been established and have made their way into treatment guidelines. Two currently available guidelines are widely accepted, one is published by the Infectious Diseases Society of America (IDSA) [3], the other by the International Lyme and Associated Diseases Society (ILADS) [4]. The two guidelines propose strikingly different approaches for the treatment of late stage Lyme disease.

Previous studies usually included patients that were diagnosed with Lyme borreliosis based on clinical and serologic findings most of which were in an early stage of the disease [5,6]. These serological criteria were introduced primarily for epidemiologic purposes reasons and lack sensitivity [4,7] for clinical use. It is doubtful whether results obtained from these studies can be generalized and applied to other cases of lyme disease. Articles that document cases diagnosed by detection of borrelial DNA have, to our knowledge, been limited to case reports and case series [8,9]. For this article we have gathered a large number of patients that were diagnosed with late stage lyme disease based on clinical and serological findings as well as direct evidence of the causative microorganism by using polymerase chain reaction (PCR). We provide long term follow up on the clinical course and treatment of these patients and evaluate the efficacy of prolonged courses (range 6-60 months) of antibiotics in these patients.

Patients

Patients sought medical attention between 1998 and 2007 because of persistent symptoms despite a presumably adequate course of antibiotics for Lyme disease. To be included in this analysis the patients had to have demonstrable Borrelia DNA (PCR method) in a skin sample in conjunction with the presence of clinical signs and symptoms consistent with Lyme disease.

Patient characteristics:

- Borrelia DNA detected in skin biopsies of all patients
- Despite adequate course of antibiotics in the past ongoing symptoms and signs most typical for Lyme Disease
- 36,66% (33/90) of patients were male, 63,33% (57/90) were female
- All age groups present, mean age 49, range 7- 88 years
- 42,22% (38/90) recalled skin rash consistent with erythema migrans
- Increased LFTs in 19% of patients
- Mean duration of illness 9,5 years (range 1-40 years) as shown in figure 1

illustration not visible in this excerpt

Figure 1: Duration in years from onset of symptoms until first administration of antibiotics (Only data from 76/90 patients was available)

The most commonly reported symptoms were fatigue, musculoskeletal and neuropsychiatric complaints (see figure 2). This observation is similar to that found in the current literature. [10, 11]. The severity of the symptoms ranged from relatively mild to disabling. Most patients had already seen many specialists about their persistent complaints.

To be included in the study the patients had to have skin manifestations, in most cases clinically diagnosed acrodermatitis chronica atrophicans or recurrent erythema migrans as a manifestation of disseminated disease.
Abbildung in dieser Leseprobe nicht enthalten Figure 2: The frequency of clinical symptoms and findings. 1*. Neuropsychiatric, 2 *. Musculo- skeletal 3 *. Fatigue, 4 *. Gastrointestinal [10], 5 *. Eye manifestations, 6 *. Cardiac, 7 *. History of Erythema migrans 8 *. Hypertension, 9 *. Thyroid disease

Many of the patients had serologic evidence of coinfections (e.g. Chlamydia spp., Mycoplasma spp., Yersinia enterocolitica or others) or non- infectious comorbidities. We evaluated 42/ 90 patients for coinfections. 80,6% (25/31) were positive for Chlamydia spp., 78,3 % (18/23) for Mycoplasma spp. and 77,8% for Yersinia (7/9). The seroprevalence of these infections was considerably higher among our sample than the seroprevalence reported among the general population [12, 13, 14]. The reasons for this surprising finding are unclear, although one could speculate that our patient sample was more prone to infection than the general population because of their persistent Lyme disease. Treatment was considered in cases of detectable IgM/ IgA response. Coinfected patients tended to have more severe disease and often needed combination therapy.

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