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PubMed2003

[Heterogeneity of Borrelia burgdorferi: etiopathogenetic relevance and clinical implications].

Of the ten different species of Borrelia (B.) burgdorferi sensu lato which have been characterized to date, only B. burgdorferi sensu stricto, B. garinii and B. afzelii have been identified as pathogenic in humans. It was suggested that different species possess different organotropisms and may preferentially cause distinct clinical manifestations of Lyme disease. Molecular analyses revealed a strong association of B. afzelii with the late cutaneous manifestation acrodermatitis chronica atrophicans, whereas B. garinii was predominantly identified in clinical samples from patients with neuroborreliosis. PCR-based analyses of samples from European patients with Lyme arthritis had given controversial results, but B. burgdorferi sensu stricto appears to be the major pathogen. The identity of the infecting species seems to be a major determinant in the pathogenesis of Lyme arthritis, although its complex immunopathological background and its clinical heterogeneity clearly indicate concomitant factors. Thus, characterization of the infecting organism at the species level on the one hand and linkage of clinical data with pathogenetically relevant immune parameters on the other, shall lead to a more precise understanding of the pathogenesis and the individual clinical course of Lyme borrelioses.

Borrelia burgdorferi↗

PubMed2003

[Epidemiology and therapy of Lyme arthritis and other manifestations of Lyme borreliosis in Germany: results of a nation-wide survey].

AIM OF THE STUDY: Only little is known about the epidemiology of Lyme borreliosis in Germany. As an example, it is still unclear if there are regional differences in the incidence of Lyme disease in general or of certain clinical manifestations like Lyme arthritis. Moreover, standardization of diagnostic or therapeutic procedures does not exist. Therefore, a Germany-wide questionnaire-based survey was conducted in order to achieve more epidemiological data and to obtain more information about the diagnostic and therapeutic approaches of general practitioners and specialists. METHODS: A self-designed questionnaire was distributed along with two editions of the journal "Deutsches Arzteblatt" (which is delivered to every physician in Germany) and additionally by a pharmaceutical company. During the collection period from March 1, 1998 to February 28, 1999, patients with Lyme disease were reported and information was given about site of infection, diagnostic procedures, clinical symptoms, treatment, and outcome. RESULTS: Altogether 3935 patients were reported. Their mean age was 43.4 years with the peak incidences around the ages of 10 and 60 years. 37.3% of the questionnaires were sent in by general practitioners, 17.6% by dermatologists, 15.7% by pediatricians, 9.7% by internists, and 2.7% by neurologists. 83% of the patients did not have a special infecion risk. The most frequent clinical Lyme manifestation was erythema migrans (EM), which occurred in 50.9% of the patients. 21.3% suffered from general symptoms. Of special interest, 24.5% of the patients had Lyme arthritis (14.7% mon- or oligoarthritis, 9.8% polyarthritis). Therefore, arthritis was more frequently reported than neuroborreliosis (18.4%). Only 16% of the neuroborreliosis patients and 32% of the arthritis patients remembered having had an EM. 189 patients (4.8%) with lymphadenosis cutis benigna and 100 patients (2.5%) with acrodermatitis chronica atrophicans were reported. In 80.4% of the patients, positive Lyme serology was detected. In a few cases, the diagnosis was established by isolation of borreliae, PCR or histology. 3754 patients were treated by antibiotics. The most frequently used compounds were doxycycline (50.4%), followed by ceftriaxone (22.4%), amoxicillin (13.6%), penicillin (7%), and erythromycin (4.2%) with differences depending on clinical manifestations and specialization of the prescribing physician. In less than 10% of the cases, not evaluated or recommended therapeutic procedures were performed. DISCUSSION: Lyme disease is endemic throughuot Germany. The most frequent manifestations are EM, followed by Lyme arthritis and neuroborreliosis. Less than one third of patients suffering from disseminated or chronic Lyme disease remembered an EM. Most of the physicians taking part in this survey follow treatment recommendations concerning choice of antibiotics and treatment durations.

Adolescent↗

PubMed1998

Stages and syndromes of neuroborreliosis.

To ascertain the varieties of neuroborreliosis, 330 patients were identified at the Departments of Neurology in Würzburg and Giessen from 1979 to 1994. Patients who fullfilled at least one of three strict case definitions based on clinical and laboratory criteria were included in the study. Ninety-one per cent of the patients had second-stage neuroborreliosis (duration of symptoms < or = 6 months). The most common syndrome was a painful spinal meningoradiculitis, alone (37%) or in combination with a cranial radiculitis (29%). Meningoradiculitis cranialis (9%), isolated meningitis (4%) and erythema chronica migrans-associated mono/polyneuritis (3%) were further stage II features. Central nervous system involvement occurred either as an acute meningomyelitis or meningomyeloradiculitis (5%) and meningoencephalitis or meningenocephaloradiculitis (4%). Less than 9% of the patients ran a chronic course (stage III) with a disease duration between 6 months and 9 years, either as acrodermatitis chronica atrophicans associated mono- or polyneuritis (2%) or a chronic progressive encephalomyelitis (6%). Cerebrovascular neuroborreliosis (1%) occurred in both stages; however, the primary nature of the course was a chronic one. Involvement of other organs except the skin was rare (joints 3%, heart 1%) but elevated hepatic enzymes were frequent. Our study demonstrates that neuroborreliosis has to be considered in the differential diagnosis of a wide variety of neurological conditions. Cerebrospinal fluid analysis and the search for specific intrathecal antibody production are important diagnostic procedures.

Adolescent↗

PubMed2000

Full spectrum of clinical, serological, and epidemiological features of complicated forms of Lyme borreliosis in the Paris, France, area.

The aim of this study was to report the clinical, serological and epidemiological features of a homogeneous cohort of patients with various forms of Lyme borreliosis, based on recent European case-definition guidelines. Complete clinical and epidemiological reports were requested from the patients' physicians for case definition. Enzyme immunoassay IgG and IgM screening tests were performed. A total of 170 patients (141 adults and 29 children) with the following forms of Lyme borreliosis were included between 1989 and 1997: erythema migrans alone (n = 38), early neuroborreliosis (n = 76), arthritis (n = 34), acrodermatitis chronica atrophicans (n = 12), carditis (n = 2), lymphocytoma (n = 3), chronic neuroborreliosis (n = 2), and miscellaneous disorders (n = 3). On the basis of the occurrence and course of the full spectrum of complicated forms of Lyme borreliosis, the specificity of the clinical and biological presentation of the complicated forms (age, ratio of children/adults, sex ratio, incubation period, time to diagnosis, and serological profiles) was demonstrated, as was the absence of overlap between the clinical presentations. Using these data, an alternative scheme for the natural history of Lyme borreliosis is suggested.

Adolescent↗

PubMed2001

Disease expression of Lyme borreliosis in northeastern France.

Since very little is known about the clinical expression of Lyme borreliosis in Western Europe, a 3-year prospective study was conducted that included all patients seen for suspected Lyme borreliosis at the Strasbourg University Hospital in northeastern France. The diagnosis of Lyme borreliosis was made on the basis of the presence of erythema migrans or on the basis of another suggestive clinical manifestation and laboratory confirmation. A total of 132 patients, 70 women and 62 men, mean age 54 years, had Lyme borreliosis according to these criteria. Within this study group, 77% of the patients were regularly exposed to tick bites and 64% could remember one. Erythema migrans, the most frequent clinical manifestation, occurred in 60% of the patients and was the only sign of Lyme borreliosis in 40%. Lymphocytoma and acrodermatitis chronica atrophicans were rare (1 and 3 patients, respectively). Nervous system involvement (mainly radiculoneuropathy), the second most common clinical manifestation, was found in 40% of the patients and was the only sign of Lyme borreliosis in 22%. Musculoskeletal involvement was present in 26% of the patients and was an isolated finding in 14%. During the study period, no patient was diagnosed with Lyme carditis. There was serological evidence of Lyme borreliosis in 75% of the cases and direct evidence of borrelial infection in 10 (7.5%). The results show that the clinical expression of Lyme borreliosis in northeastern France is similar to that in other European countries but different from that in North America.

Adolescent↗

PubMed1989

Myositis caused by Borrelia burgdorferi: report of four cases.

Myositis was proven histopathologically in 4 patients (age range 36-66 years) who suffered from early or late stages of Borrelia burgdorferi infection. Muscle weakness was present in 3 patients, 1 complaining of additional myalgias. One man came to medical attention because of skin discoloration and swelling of one leg. Deep biopsy from skin, fascia and muscle revealed acrodermatitis chronica atrophicans, panniculitis, fasciitis, and myositis, respectively. Creatine kinase was slightly elevated in 3 cases and normal in one. Infiltrates were found in the perimysium and within the muscle bundles, mainly around small vessels. The infiltrates consisted of many B cells and T4 lymphocytes with fewer cytotoxic T cells, suggesting that Borrelia myositis might be due to a local immune response to unknown Borrelia antigens. Cultivation of Borrelia from muscle was not successful. Antibiotic therapy cured the myositis.

Adult↗

PubMed1993

Localized scleroderma associated with Borrelia burgdorferi infection. Clinical, histologic, and immunohistochemical observations.

BACKGROUND: Recent reports have implicated Borrelia burgdorferi infection as a possible cause of localized scleroderma (LS). OBJECTIVE: Our purpose was to describe the clinical, histologic, and immunopathologic features of patients with LS who had serum antibodies to B. burgdorferi. METHODS: Ten patients were examined clinically and by routine microscopy. Biopsy specimens from seven patients were studied immunohistochemically with monoclonal antibodies. The proliferative response of peripheral blood mononuclear cells to B. burgdorferi was investigated in seven patients by lymphocyte proliferation assay. RESULTS: Seven patients had plaque-type morphea, and three patients had linear scleroderma. Two patients had a history of previous erythema migrans. One patient had coexistent acrodermatitis chronica atrophicans, and in two patients lichen sclerosus et atrophicus was observed. Histologically, a prominent inflammatory phase with sclerosis of the connective tissue was shown in all patients. Immunohistochemical studies revealed that the inflammatory infiltrates consisted of both B and T lymphocytes, predominantly of the CD4+ subset. All 10 patients had strongly elevated serum antibodies to B. burgdorferi. Patients with LS showed significantly elevated lymphoproliferative responses to B. burgdorferi when compared with healthy control subjects. CONCLUSION: Our findings suggest that some cases of LS are linked to Borrelia infection.

Adolescent↗

PubMed1995

Detection of Borrelia burgdorferi DNA by polymerase chain reaction in the urine and breast milk of patients with Lyme borreliosis.

Current laboratory diagnosis of Lyme borreliosis relies on tests for the detection of antibodies to Borrelia burgdorferi with known limitations. By using a simple extraction procedure for urine samples, B. burgdorferi DNA was amplified by a nested PCR with primers that target the specific part of the flagellin gene. To control possible inhibition of the enzyme (polymerase), a special assay using the same primers was developed. We examined 403 urine samples from 185 patients with skin manifestations of Lyme borreliosis. Before treatment, B. burgdorferi DNA was detected in 88 of 97 patients with Lyme borreliosis. After treatment, all but seven patients became nonreactive. Six of these seven persons suffered from intermittent migratory arthralgias or myalgias, and one from acrodermatitis chronica atrophicans. Two of 49 control patients with various dermatologic disorders and none out of 22 presumably healthy persons were reactive in the PCR. In addition to urine, breast milk from two lactating women with erythema migrans was tested and also found reactive. Borrelia burgdorferi DNA can be detected with high sensitivity (91%) by a nested PCR in urine of patients with Lyme borreliosis. In addition, this test can be a reliable marker for the efficacy of treatment.

Animals↗

PubMed1989

Lyme borreliosis in Finland in 1986-1988.

In 1986-1988 there were 123 patients with positive serology for Lyme borreliosis out of 4000 sera referred to the Department of Bacteriology and Immunology, University of Helsinki. Of the 63 patients with positive serology in 1986-1987 20 showed a predominant involvement of the nervous system, 18 complained of joint symptoms and 11 patients merely showed a skin involvement including 8 patients with erythema chronicum migrans (ECM) and 3 patients with acrodermatitis chronica atrophicans (ACA). Two of the patients had unspecific general symptoms and in 5 patients the type of involvement remained unknown. The serology was considered to be falsely positive in 2 patients with tuberculous meningitis, in one with syphilis and in another with recurrent fever.

Adult↗

PubMed2005

Susceptibility of Borrelia afzelii strains to antimicrobial agents.

The aim of the present study was to determine the susceptibility of Borrelia afzelii strains to antibiotics, and to test the hypothesis that persistence of borrelia in skin, after therapy, is a consequence of resistance to the antibiotic used for treatment. Ten B. afzelii strains isolated from skin of seven adult patients (two with acrodermatitis chronica atrophicans, five with erythema migrans) were studied. In three patients B. afzelii was isolated from erythema migrans lesion before antibiotic therapy and 2-3 months after treatment with cefuroxime axetil (two patients) or with ceftriaxone (one patient). MICs and MBCs for amoxicillin, azithromycin, ceftriaxone, cefuroxime, doxycycline and amikacin were measured. There was total resistance to amikacin but isolates were susceptible to all other antibiotics except one isolate that was resistant to cefuroxime, MIC > 4 mg/L. Comparison of MBC values after 3 and 6 weeks' incubation revealed comparable results for azithromycin and ceftriaxone while for amoxicillin, cefuroxime and doxycycline, some differences were found. In one of the patients from whom there were borrelia isolated before and after treatment with cefuroxime axetil, both isolates were resistant to cefuroxime. In the other two patients, the paired isolates were susceptible to the antibiotic used for therapy.

Adult↗

PubMed2003

Phenotypes indicating cytolytic properties of Borrelia-specific interferon-gamma secreting cells in chronic Lyme neuroborreliosis.

The immuno-pathogenetic mechanisms underlying chronic Lyme neuroborreliosis are mainly unknown. Human Borrelia burgdorferi (Bb) infection is associated with Bb-specific secretion of interferon-gamma (IFN-gamma), which may be important for the elimination of Bb, but this may also cause tissue injury. In order to increase the understanding of the pathogenic mechanisms in chronic neuroborreliosis, we investigated which cell types that secrete IFN-gamma. Blood mononuclear cells from 13 patients with neuroborreliosis and/or acrodermatitis chronicum atrophicans were stimulated with Bb antigen and the phenotypes of the induced IFN-gamma-secreting cells were analyzed with three different approaches. Cells expressing CD8 or TCRgammadelta, which both have cytolytic properties, were the main phenotypes of IFN-gamma-secreting cells, indicating that tissue injury in chronic neuroborreliosis may be mediated by cytotoxic cells.

Adult↗

PubMed1995

Muscle, reticuloendothelial, and late skin manifestations of Lyme disease.

In addition to classic organ system involvement, Lyme disease may be characterized by myositis, liver and spleen involvement, and atypical cutaneous manifestations. Myositis is characteristically localized near an involved joint or localized neuropathy. Nuclear imaging with gallium-67 may be useful for detection. Myositis responds to treatment with intravenous or oral antibiotics. Patients with erythema migrans have been observed to have liver function test abnormalities in the absence of symptomatic hepatitis. Splenomegaly has been noted infrequently in patients with Lyme disease. Chronic cutaneous manifestations of Lyme disease--including erythema migrans, acrodermatitis chronica atrophicans, and lymphadenosis benigna cutis--have been observed more frequently in Europe than in the United States. It appears that they are caused primarily by the Borrelia afzelii genomic group of Borrelia burgdorferi, which has been found exclusively in Europe.

Europe↗

PubMed2003

Lyme borreliosis.

Lyme borreliosis is the most common tick-transmitted disease in the northern hemisphere and is caused by spirochaetes of the Borrelia burgdorferi species complex. A complete presentation of the disease is an extremely unusual observation in which a skin lesion results from a tick bite and is followed by heart and nervous system involvement, and later on by arthritis. Late involvement of eye, nervous system, joints, and skin can also occur. The only sign that enables a reliable clinical diagnosis of Lyme borreliosis is erythema migrans. Other features of some diagnostic value are earlobe lymphocytoma, meningoradiculoneuritis (Garin-Bujadoux-Bannwarth syndrome), and acrodermatitis chronica atrophicans. The many other symptoms and signs have little diagnostic value. Microbial or serological confirmation of borrelial infection is needed for all manifestations of the disease except for typical early skin lesions. However, even erythema migrans might not be pathognomonic for Lyme borreliosis, especially in the southern part of the USA where there is no microbiological evidence for infection with the agent. Treatment with antibiotics is beneficial for all stages of Lyme borreliosis, but is most successful early in the course of the illness. Prevention relies mainly on avoiding exposure to tick bites but there is some interest in chemoprophylaxis and also in vaccine development following initial disappointments.

Humans↗

PubMed1986

Microbiological findings in erythema (chronicum) migrans and related disorders.

In order to evaluate the virtual advantage of proving borrelial infection in dermatoses clinically diagnosed as erythema (chronicum) migrans (ECM), acrodermatitis chronica atrophicans (ACA) or lymphadenosis cutis benigna (LCB) by means of histological, cultural or serological trials, skin and serum samples obtained from altogether 99 patients suffering from these dermatoses were examined. Serum and--to some extent--skin specimens gained from healthy individuals (n = 36), patients with not tick bite associated disorders of skin, internal organs and nervous system (n = 121) were used as controls. In addition, serum specimens from patients enduring circumscribed scleroderma (morphea), n = 31, and sera of Bavarian forest workers (n = 211) were proven for the presence of borrelial antibodies. Using an indirect immunofluorescence assay with borrelial strains, propagated in inbred mice, as antigens, elevated IgM- and/or IgG antibody titers were found in 51 (84%) out of 61 ECM-, in 17 (100%) ACA- and in 2 (33%) out of 6 LCB-sera. Antibody titers decreased significantly after adequate antibiotic therapy. The groups in comparison yielded spirochetal serum antibodies as follows: Healthy individuals and patients with various diseases 7 out of 157 (4.5%), morphea patients 7 out of 31 (23%) and forest workers 71 out of 211 (34%). Borrelia burgdorferi was cultivated from 6 out of 32 skin and from 1 blood specimen obtained from ECM patients and from 1 out of 5 ACA skin specimens. Borreliae could also be detected in the blood of 3 out of 11 thymusaplastic nude mice after intraperitoneal implantation of ECM-tissue. More frequently than borreliae spindle-shaped bacteria resembling fusobacterium sp. were detected not only by in vitro cultivation of ECM and ACA skin samples, but also in the blood of thymusaplastic mice after implantation of ECM-tissue. By Warthin-Starry silver strain borrelia-like structures were detected in 9 out of 28 ECM, in 3 out of 12 ACA and in 1 out of 5 LCB skin specimens. Therefore in our experience serological examinations turned out to be the most productive diagnostic tool.

Adolescent↗

PubMed2003

Lyme borreliosis.

Lyme borreliosis is a multi-organ infection caused by spirochetes of the Borrelia burgdorferi sensu lato group with its species B burgdorferi sensu stricto, Borrelia garinii, and Borrelia afzelii, which are transmitted by ticks of the species Ixodes. Laboratory testing of Lyme borreliosis includes culture, antibody detection using ELISA with whole extracts or recombinant chimeric borrelia proteins, immunoblot, and PCR with different levels of sensitivity and specificity for each test. Common skin manifestations of Lyme borreliosis include erythema migrans, lymphocytoma, and acrodermatitis chronica atrophicans. The last two conditions are usually caused by B garinii and B afzelii, respectively, which are seen more frequently in Europe than in America. Late extracutaneous manifestations of Lyme borreliosis are characterised by carditis, neuroborreliosis, and arthritis. We present evidence-based treatment recommendations for Lyme borreliosis and review the prevention of Lyme borreliosis, including the Lyme vaccines.

Adolescent↗

PubMed2001

Detection and molecular typing of Borrelia burgdorferi sensu lato in Ixodes ricinus ticks and in different patient samples from southwest Germany.

The prevalence of different genospecies of Borrelia burgdorferi sensu lato in infected ticks could be a determinant for the risk of acquiring Lyme borreliosis (LB) and its clinical presentation. A total of 7373 ticks and 2761 samples from LB patients from the same area in southwest Germany were analyzed by PCR to assess the frequency of the occurrence of LB-associated genospecies. Fifteen percent of the tick samples and 19% of the human samples were found positive for the presence of B. burgdorferi sensu lato. Further identification of 1106 B. burgdorferi sensu lato positive tick samples by reverse line blotting and 125 positive patient samples by nested PCR using species-specific primers revealed the occurrence of B. afzelii, B. burgdorferi sensu stricto, B. garinii and B. valaisiana. Both single-species and mixed infections were noted and a similar distribution of the different genospecies was found in ticks compared with human samples. It was also the purpose of this study to obtain more information about a possible correlation between the distribution of Borrelia species and clinical syndromes of LB. Skin biopsies of 59 patients with acrodermatitis chronica atrophicans and cerebrospinal fluid samples from 78 patients with possible neuroborreliosis were analyzed. In conclusion, the distribution of the different genospecies in ticks is the decisive factor for the occurrence of the different Borrelia genospecies in samples from LB patients. Borrelia afzelii is the predominant genospecies in all kind of samples from the observed area and there seems to be no association of particular Borrelia genospecies with distinct clinical manifestations of LB.

Animals↗

PubMed2000

Morphoea is neither associated with features of Borrelia burgdorferi infection, nor is this agent detectable in lesional skin by polymerase chain reaction.

BACKGROUND: The aetiology of morphoea is still unknown. Borrelia burgdorferi as a causative agent of morphoea has been discussed since 1985, but the relationship remains uncertain. OBJECTIVES: We aimed to find evidence for infection with B. burgdorferi by combined evaluation of different clinical and laboratory data in a group of 54 patients with morphoea. METHODS: In each patient, an evaluation of the case history was performed with regard to infection with B. burgdorferi, using a standardized questionnaire. Questions focused on previous tick bites and skin changes suspicious for erythema migrans (EM). The case history data of 52 patients were compared with those of 104 matched control subjects and of 25 patients with acrodermatitis chronica atrophicans (ACA). Serological examinations were performed in 53 patients with morphoea. Furthermore, lesional skin was examined for borrelial DNA in 33 patients, using nested polymerase chain reaction (PCR) for the ospA and the borrelial rRNA gene. RESULTS: Results of the questionnaire showed no differences between patients with morphoea and matched controls. In contrast, patients with ACA showed a much higher prevalence of tick bites and skin changes suspicious for EM as compared with patients with morphoea. Serological examination was positive in only one patient with morphoea alone and in two additional patients with coexistent ACA. No borrelial DNA was detected by PCR in lesional skin of 33 patients with morphoea. CONCLUSIONS: No evidence was found for B. burgdorferi infection in patients with morphoea.

Adolescent↗

PubMed1999

Enhanced expression of human metalloelastase (MMP-12) in cutaneous granulomas and macrophage migration.

Accumulation of inflammatory cells such as macrophages may lead to degeneration of connective tissue matrix in various skin diseases. Macrophage metalloelastase, is a matrix metalloproteinase (MMP-12) capable of degrading elastin as well as various basement membrane components. To investigate the role of human macrophage metalloelastase in skin, we assessed by in situ hybridization and immunohistochemistry 66 specimens representing skin diseases characterized either by changes in elastic fibers or by pronounced infiltrations of extravasating and migrating macrophages. CD68 immunostaining was performed to identify the human macrophage metalloelastase-positive cells and Weigert's Resorcin-Fuchsin staining to reveal the status of elastic fibers. We found abundant expression of human macrophage metalloelastase mRNA in macrophages in areas devoid of normal elastic fibers in granulomatous skin diseases sarcoidosis, necrobiosis lipoidica diabeticorum, and granuloma annulare. Positive cells for human macrophage metalloelastase protein could be detected in the same regions as well as positive immunostaining for urokinase plasminogen activator. Of the other matrix metalloproteinases capable of degrading elastin, 92 kDa gelatinase colocalized with human macrophage metalloelastase, while 72 kDa gelatinase was produced by surrounding fibroblast-like cells. Furthermore, human macrophage metalloelastase was expressed by macrophages in areas with disrupted basement membrane, as assessed by type IV collagen staining, in pityriasis lichenoides and dermatitis herpetiformis. Specimens of anetoderma, acrodermatitis chronica atrophicans and pseudoxanthoma elasticum showed no signal for human macrophage metalloelastase. Matrilysin was not detected in any of the samples investigated. Our study suggests that human macrophage metalloelastase may contribute to elastin degradation occurring in granulomatous skin diseases and may aid macrophage migration through the epidermal and vascular basement membranes in inflammatory disorders.

Cell Movement↗