Guidelines for diagnosis and treatment in neurology - Lyme neuroborreliosis.

Lyme borreliosis is the most common tick-borne infectious disease in Europe. A neurological manifestation occurs in 3-15% of infections and can manifest as polyradiculitis, meningitis and (rarely) encephalomyelitis. This S3 guideline is directed at physicians in private practices and clinics who treat Lyme neuroborreliosis in children and adults. Twenty AWMF member societies, the Robert Koch Institute, the German Borreliosis Society and three patient organisations participated in its development. A systematic review and assessment of the literature was conducted by the German Cochrane Centre, Freiburg (Cochrane Germany). The main objectives of this guideline are to define the disease and to give recommendations for the confirmation of a clinically suspected diagnosis by laboratory testing, antibiotic therapy, differential diagnostic testing and prevention.

[Clinical and Laboratory Predictors for Forecasting the Outcomes of Ixodes Tick-Borne Borreliosis].

OBJECTIVE: Our aim was to identify the most informative clinical and laboratory predictors of chronicity of Ixodes tick-borne borreliosis in the acute phase of the disease based on the "optimal cut-off values" (COV) and the predicted probability of the outcomes. METHODS: A retrospective cohort controlled study was carried out. We used the technique of ROC-analysis to estimate the information content of the clinical and laboratory indicators in patients with Ixodes tick-borne borreliosis in the acute phase of the disease with erythemal (n =16), non-erythemal (n = 77) forms of Ixodes tick-borne borreliosis and co-infection with the tick-borne encephalitis (n = 68) for the prediction of the outcomes: recovery or chronization. RESULTS: A retrospective analysis of clinical and laboratory parameters recorded in the acute phase of the disease in 161 patients with chronic Ixodes tick-borne borreliosis. The calculations were performed for the informative clinical and laboratory prognostic predictors of the outcomes for the intervals above and below the COVvalues are defined probabilities of recovery or chronization of Ixodes tick-borne borreliosis. A general predictor of outcomes for all clinicalforms of the disease--the interleukin 8--was established: the probability of chronization after erythemal form is 100.0% at the level of its production over 107.89 pg/ml (AUC = 1.0), after non-erythemal form is 54.63 ± 0.23% at serum concentrations above 94.64 pg/ml (AUC = 0.770), after co-infection with the tick-borne encephalitis is 52.69 ± 0.27% at the level of interleukin 8 above 84.96 pg/ml (AUC = 0.780). CONCLUSION: The results of the study suggest the possibility of predicting the outcomes of infection in the acute phase, which allows to optimize the etiopathogenic therapy of the disease in a timely manner.

Clinical spectrum of skin manifestations of Lyme borreliosis in 204 children in Austria.

The spectrum of skin manifestations of Lyme borreliosis in children is not well characterized. We conducted a retrospective study to analyze the clinical characteristics, seroreactivity to Borrelia burgdorferi sensu lato, and outcome after treatment in 204 children with skin manifestations of Lyme borreliosis seen in 1996-2011. Solitary erythema migrans was the most common manifestation (44.6%), followed by erythema migrans with multiple lesions (27%), borrelial lymphocytoma (21.6%), and acrodermatitis chronica atrophicans (0.9%). A collision lesion of a primary borrelial lymphocytoma and a surrounding secondary erythema migrans was diagnosed in 5.9% of children. Rate of seroreactivity to B. burgdorferi s.l. was lower in solitary erythema migrans compared to other diagnosis groups. Amoxicillin or phenoxymethylpenicillin led to complete resolution of erythema migrans within a median of 6 (solitary) and 14 days (multiple lesions), respectively, and of borrelia lymphocytoma within a median of 56 days. In conclusion, erythema migrans with multiple lesions and borrelial lymphocytoma appear to be more frequent in children than in adults, whereas acrodermatitis chronica atrophicans is a rarity in childhood. The outcome after antibiotic therapy was excellent in children, and appears to be better than in adults.

Subjective symptoms after treatment of early Lyme disease.

BACKGROUND: Controversy exists over the significance and even the existence of post-Lyme disease symptoms because of the high rate of similar background symptoms in the general population. METHODS: A European, prospective clinical trial in which doxycycline and cefuroxime axetil were compared in the treatment of adult patients with erythema migrans included a control group to address this question. Evaluations of patients were conducted at baseline, 14 days, and 2, 6, and 12 months after enrollment. Control subjects were evaluated at baseline and at 6 and 12 months. Subjective symptoms that newly developed or intensified since the onset of erythema migrans or the date of enrollment for controls were referred to as "new or increased symptoms." RESULTS: Doxycycline and cefuroxime axetil had comparable efficacy. At both 6 and 12 months, the frequency of new or increased symptoms in patients with erythema migrans did not exceed the frequency of such symptoms in a control group of individuals of similar gender and age without a clinical history of Lyme disease. At 12 months after enrollment, only 5 (2.2%) of 230 evaluable patients reported new or increased symptoms, and in none of the patients were these symptoms of sufficient severity to be functionally disabling. CONCLUSION: No significant differences were identified between doxycycline and cefuroxime axetil in the treatment of European patients with erythema migrans. The frequency of nonspecific symptoms in patients did not exceed that of a control group at > or =6 months after enrollment. We advocate inclusion of appropriate non-Lyme disease control groups in future studies in which nonspecific subjective symptoms are assessed after antibiotic therapy.

Immune complexes in early Lyme disease.

The study investigated the presence of Borrelia-specific antibodies captured in immune complexes (ICs) in patients with early Lyme disease manifested by erythema migrans. Out of 18 patients, 15 (83.3%) tested positive for polyethylene glycol-precipitated ICs containing IgM antibodies, while only 4 (22.2%) were IgG positive. These results are in accordance with our findings obtained by standard ELISA and recombinant blot, which indicated that ICs might be used for serological diagnosis of the early disease.

Electrocardiographic findings in children with erythema migrans.

OBJECTIVE: To assess electrocardiographic findings in children with erythema migrans and to compare them with findings obtained in a healthy control group of comparable age and with a similar proportion of boys and girls. METHODS: Electrocardiograms were carried out in 147 children under the age of 15 years before treatment with antibiotics for erythema migrans (solitary 68 patients, multiple 79 patients) and in the control group of 148 healthy children. RESULTS: Abnormal electrocardiographic findings were detected more often in healthy children than in patients (14% versus 5%; P = 0.0303) and among patients more often in boys than in girls (10% versus 0%; P = 0.0107). Electrocardiographic abnormalities characteristic for Lyme borreliosis, such as atrioventricular blocks, were rare: in patients with erythema migrans only one child had first-degree atrioventricular block; in the control group one child had first-degree and another had second-degree atrioventricular block. Patients with erythema migrans had shorter PR and RR intervals and lower R and S wave voltages in V1 than the healthy children. Comparison among patients with solitary and multiple erythema migrans did not reveal significant electrocardiographic differences. The frequency of electrocardiographic abnormalities in patients with erythema migrans was not associated with the presence of systemic symptoms, or with the presence of meningitis or the isolation of Borrelia burgdorferi sensu lato from the blood. CONCLUSIONS: Electrocardiographic abnormalities in children with erythema migrans are mild, nonspecific and rare. The presence of clinical signs and symptoms indicative or suggestive of disseminated Lyme borreliosis is not associated with higher frequency of such abnormalities. Comparison of findings in patients with erythema migrans and healthy children revealed several distinctions, some of which might have been interpreted as a result of altered activity of the autonomic nervous system.

Current diagnosis and treatment of lyme disease.

In more than 80% of cases, Lyme disease presents with an erythema migrans rash, but its characteristics can vary. Carditis, cranial palsies, lymphocytic meningitis, oligoarticular arthritis are manifestations of disseminated infection. Serological tests are helpful, but must be interpreted with caution. Standard antibiotic treatment regimens are highly effective.

Comparison of erythema migrans caused by Borrelia afzelii and Borrelia garinii.

BACKGROUND: We compared epidemiological and clinical characteristics of patients with erythema migrans (EM) caused by Borrelia afzelii and Borrelia garinii. PATIENTS AND METHODS: 200 consecutive adult patients with B. afzelii isolated from the skin lesion and 53 consecutive adult patients with EM caused by B. garinii qualified for the present study. RESULTS: Comparison of the two groups revealed several distinctions. Patients with EM caused by B. garinii were older, had their skin lesions more often located on the trunk but less often on extremities, had shorter incubation and faster evolution of EM, more often reported associated local and certain systemic symptoms, had abnormal liver function test results more often and were more frequently seropositive. CONCLUSION: Early localized Lyme borreliosis caused by B. afzelii and B. garinii has distinct epidemiological and clinical characteristics. Clinical features of EM depend upon the genospecies of Borrelia burgdorferi sensu lato causing the illness.

Characteristics of erythema migrans in Borrelia afzelii and Borrelia garinii infections.

Erythema migrans is the most common manifestation of stage I Lyme borreliosis. This study investigated the relation between the subspecies of Borrelia burgdorferi involved, the time of development and the appearance of the manifestation. The study comprised 33 cases of erythema migrans yielding B. burgdorferi sensu lato by culture of skin biopsy. The species was determined by polymerase chain reaction analysis of the cultivated spirochaetes. In 22 of the cases, B. afzelii was demonstrated, whereas 11 yielded growth of B. garinii. All 11 erythemas associated with B. garinii were homogeneous, whereas 20 of the 22 associated with B. afzelii were annular. The garinii erythemas developed more rapidly, and were generally larger than the afzelii erythemas. The observations call for comparison with other geographical areas with similar, and with different, borrelial infection spectra.

Electrocardiographic findings in patients with erythema migrans.

OBJECTIVE: To identify asymptomatic heart involvement early in the course of Lyme borreliosis by analysis of electrocardiograms (ECGs) of patients with solitary erythema migrans (EM). METHODS: We enrolled in this prospective study 220 consecutive previously healthy patients, receiving no medication, who were diagnosed with typical solitary EM at our Lyme borreliosis Outpatient Clinic in 1998. Their ECG findings were compared with the ECG results in 165 age and sex-matched healthy persons. RESULTS: Three patients with EM but none in the control group had first degree AV block (p = 0.319). Second and third degree AV blocks, electrocardiographic signs of pericarditis, myocarditis or rhythm disturbances were not found in any of the ECGs. Comparison of findings in patients with EM and the control group revealed statistically significant differences in frequency (66.2 +/- 1.47 beats/min in patients with EM versus 68.4 +/- 1.52 beats/min in controls; p = 0.043), duration of Q (0.013 +/- 0.001 s in patients with EM versus 0.015 +/- 0.001 s in controls; p < 0.001), and in depth of S (0.135 +/- 0.016 mV in patients with EM versus 0.104 +/- 0.012 mV in controls; p < 0.05), but not for several other ECG parameters. These differences were found in females as well as in males. Comparison of ECG findings in subgroups of patients with EM (grouped according to EM characteristics such as length of incubation, duration of skin lesion and the presence of associated systemic symptoms) did not reveal any significant difference. CONCLUSIONS: AV blocks, the most typical heart manifestation of early disseminated Lyme borreliosis, are a rare finding in patients with solitary EM, and in our study their frequency did not differ from that in the control group. We do not have a reliable explanation for the shorter duration of Q and deeper S wave in patients with EM compared with age and sex-matched controls.

Erythema migrans and the differential diagnosis of annular erythema.

The diagnosis of Lyme disease (LD) or Lyme borreliosis is often based on the recognition of erythema migrans (EM) because its clinical appearance precedes systemic manifestations of the disease and the antibody response. The clinical basis and variable presentation of EM leave room for diagnostic error and, as a consequence, potential long-term repercussions such as rheumatic, cardiac, ophthalmic, or neurologic complications. Most cases are reported in the Northcentral and Northeastern states. In areas where LD is not endemic, the differential diagnosis of annular erythema may not list EM highly, although all the features of a lesion may fit the typical description of EM. Therefore, a complete understanding of LD and its clinical presentation are key in making a diagnosis, especially in areas with low incidence. We present a hypothetical case report of EM from Oklahoma, a state with low incidence of LD, for the purposes of review of this entity and the differential diagnosis of annular erythema.

Quantitative detection of Borrelia burgdorferi in 2-millimeter skin samples of erythema migrans lesions: correlation of results with clinical and laboratory findings.

Variability of disease manifestations has been noted in patients with Lyme disease. A contributing factor to this variation may be the number of spirochetes present in infected patients. We evaluated clinical and laboratory findings for patients with erythema migrans with regard to the number of Borrelia burgdorferi organisms detected by quantitative PCR (qPCR) in 2-mm skin biopsy specimens. B. burgdorferi was detected in 80% (40 of 50) of the specimens tested; the mean number of spirochetes in these specimens ranged over 3 orders of magnitude (10 to 11,000 spirochetes per 2-mm biopsy specimen). Larger numbers of spirochetes were significantly associated with a shorter duration of the erythema migrans skin lesion (P = 0.020), smaller skin lesions (P = 0.020), and infection with a specific genotype of B. burgdorferi (P = 0.008) but not with the number or severity of symptoms. Skin culture positivity was significantly associated with skin lesions containing larger numbers of spirochetes (P = 0.019).

Role of reactive oxygen species (ROS) in patients with erythema migrans, an early manifestation of Lyme borreliosis.

BACKGROUND: Lyme borreliosis is a tick-transmitted, chronic, zoogenous disease caused by Borrelia burgdorferi spirochete. The clinical picture of Lyme disease is characterized by the variety of tissue and organ involvement and differing severity of symptoms. One of the pathogenic symptoms of early Lyme disease is a skin lesion called erythema migrans. MATERIAL AND METHODS: The purpose of our research was to estimate the parameters of the antioxidant system and the concentration of lipid peroxidation products in the plasma of patients with erythema migrans (EM). The parameters measured included the activity levels of superoxide dismutase (SOD) according to Sykes, gluthatione reductase (GSSG-R) according to Mize and Langdon, glutathione peroxidase (GSH-Px) according to Paglia and Valentine; the concentrations of malondialdehyde (MDA) were examined by means of a Bioxytech LPO-586 kit. The total sulphydryl groups (-SH) according to Ellman and reduced glutathione (GSH) were measured using a Bioxytech GSH-400 test in plasma samples collected from 20 patients with EM aged from 19 to 50, taken before (examination 1) and after (examination 2) therapy with amoxycycline. The control group consisted of 8 healthy people. RESULTS: The results of our examinations prove that beta-lactamase antibiotic therapy brings non-enzymatic antioxidant parameters to control values, though the treatment causes no change in enzymatic antioxidant parameters, resulting in the further activation of free radicals. CONCLUSIONS: In patients with Erythema migrans, the decreased capability to reduce lipid superoxidants leads to maintaining a high concentration of membrane lipid peroxidation products.

Evaluation of study patients with Lyme disease, 10-20-year follow-up.

To determine the long-term impact of Lyme disease, we evaluated 84 randomly selected, original study patients from the Lyme, Connecticut, region who had erythema migrans, facial palsy, or Lyme arthritis 10-20 years ago and 30 uninfected control subjects. The patients in the 3 study groups and the control group did not differ significantly in current symptoms or neuropsychological test results. However, patients with facial palsy, who frequently had more widespread nervous system involvement, more often had residual facial or peripheral nerve deficits. Moreover, patients with facial palsy who did not receive antibiotics for acute neuroborreliosis more often now had joint pain and sleep difficulty and lower scores on the body pain index and standardized physical component sections of the Short-Form 36 Health Assessment Questionnaire than did antibiotic-treated patients with facial palsy. Thus, the overall current health status of each patient group was good, but sequelae were apparent primarily among patients with facial palsy who did not receive antibiotics for acute neuroborreliosis.

Association of specific subtypes of Borrelia burgdorferi with hematogenous dissemination in early Lyme disease.

To investigate whether genetic diversity of Borrelia burgdorferi sensu stricto may affect the occurrence of hematogenous dissemination, 104 untreated adults with erythema migrans from a Lyme disease diagnostic center in Westchester County, New York, were studied. Cultured skin isolates were classified into 3 groups by a polymerase chain reaction amplification and restriction fragment length polymorphism (RFLP) method. A highly significant association between infecting RFLP type in skin and the presence of spirochetemia was found (P<.001). The same association existed for the presence of multiple erythema migrans lesions (P=.045), providing clinical corroboration that hematogenous dissemination is related to the genetic subtype of B. burgdorferi sensu stricto. There were no significant associations between RFLP type and seropositivity or clinical symptoms and signs except for a history of fever and chills (P=.033). These results suggest that specific genetic subtypes of B. burgdorferi sensu stricto influence disease pathogenesis. Infection with different subtypes of B. burgdorferi sensu stricto may help to explain differences in the clinical presentation of patients with Lyme disease.

Current aspects of Lyme disease and other Borrelia burgdorferi infections.

Lyme disease, acrodermatitis chronica atrophicans, and borrelial lymphocytoma are caused by species of the spirochete Borrelia burgdorferi. Lyme disease has emerged as the leading vector-borne infectious disease in the United States. This article presents a current review of these entities.

Treatment failure in erythema migrans--a review.

Patients with erythema migrans can fail to respond to antibiotic therapy. Persistent or recurrent erythema migrans, major sequelae such as meningitis and arthritis, survival of Borrelia burgdorferi and significant and persistent increase of antibody titres against B. burgdorferi after antibiotic therapy are strong indications of a treatment failure. Most, if not all, antibiotics used so far have been associated with a treatment failure in patients with erythema migrans. Roxithromycin and erythromycin are definitely or probably ineffective. However, doxycycline, amoxicillin, cefuroxime, ceftriaxone, azithromycin and high-dose penicillin V perform comparably well.