[Multiple muscle abscesses in a Tibetan woman].
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Biomedical subjects
Publications and source records attributed to P Herzer.
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Borrelia burgdorferi sensu lato, the etiological agent of Lyme borreliosis, has been divided into three genospecies: B. burgdorferi sensu stricto (OspA-type 1), B. afzelii (OspA-type 2) and B. garinii (OspA-type 3-7). Whereas in Europe B. afzelii (OspA-type 2) is predominant among human skin isolates and B. garinii (OspA-type 3-7) among human CSF isolates, some previous serological studies suggested that Lyme arthritis is also associated with B. burgdorferi sensu stricto in Europe. In the present study we designed ospA type-specific PCRs and identified four different ospA types associated with Lyme arthritis. Our study group consisted of 20 patients with positive serology (ELISA and immunoblotting) and clinical criteria for Lyme arthritis. B. burgdorferi DNA was detected in 13 patients and in none of 10 control patients from synovial fluid. We identified ospA-type 1 (26.6%), ospA-type 2 (33.3%), ospA-type 4 (6.6%) and ospA-type 5 (33.3%). Our conclusion is that in Europe B. burgdorferi sensu lato strains causing Lyme arthritis are considerably heterogeneous and that there is no prevalence of certain genospecies or OspA-types among this strains.
Reiter's syndrome and reactive arthritis in individuals with human immunodeficiency virus (HIV) infection are characterized by severe and persistent arthritis, intense enthesopathy, and poor response to treatment. These uncommon clinical features suggest a direct role of HIV in the pathogenesis of seronegative spondylarthropathies. We report on widely differing clinical features in two HIV-infected patients with undifferentiated seronegative spondylarthropathy or reactive arthritis. Both patients were HLA-B27-positive. The first patient presented with heel swelling and dactylitis ("sausage" toes). Subsequently he developed polyarticular erosive arthritis. The clinical course was complicated by fulminant ulcerative colitis leading to hemicolectomy. After hemicolectomy, a temporary resolution of arthritis occurred. In the second patient, heel swelling and polyarticular arthritis occurred 2 months after Shigella dysentery. After 3 years of continuing joint inflammation, he presented with a Jaccoud-like arthropathy. In a cohort of 700 HIV-infected patients receiving continuous care in our department, these were the only patients with seronegative spondylarthropathy observed between 1984 and 1992.
Several distinct patterns of rheumatic manifestations can be seen throughout the course of Lyme borreliosis: intermittent and migratory musculoskeletal pain without objective findings, intermittent arthritis, chronic erosive arthritis, and joint deformities under affected skin in acrodermatitis chronica atrophicans. Commonly, Lyme arthritis is a late disease manifestation. A clinical history of extra-articular disease manifestations is the most reliable key to Lyme arthritis. However, arthritis often occurs without antecedent early-disease manifestations. The diagnostic significance of serological findings suggesting Lyme arthritis must be considered carefully with regard to the typical clinical features of Lyme arthritis and its potential differential diagnoses. Otherwise, Lyme arthritis will be frequently over-diagnosed. Lyme arthritis can be cured with antibiotics. However, treatment failures occur with any of the hitherto recommended regimens.
A recombinant immunoblot was developed for detection of IgM and IgG antibodies in patients with Lyme borreliosis. The recombinant antigens were the chromosomal-encoded Borrelia burgdorferi proteins p100, the flagellin and an internal flagellin fragment thereof as well as the plasmid-encoded outer surface proteins A (OspA) and C (OspC). A panel of 144 sera from patients with Lyme borreliosis (erythema migrans, n = 31; neuroborreliosis state II, n = 60; Lyme arthritis, n = 24 and acrodermatitis chronica atrophicans, n = 19) have been investigated and the results have been compared to the immunofluorescence absorption test (IFA-ABS) and to two different enzyme-linked immunosorbent assays [the flagellin ELISA and a newly developed ELISA (OGP-ELISA)]. The two ELISAs were comparable in sensitivity, whereas the IFA-ABS was less sensitive for IgM antibody but equally sensitive for IgG antibody detection. Immunoblot analysis revealed that IgG antibodies are mainly reactive with p100 and the internal flagellin fragment (sensitivity 51% and 32%, respectively) and rarely with OspC (14%). All patients with late Lyme borreliosis had IgG antibodies against the p100. IgM antibodies were predominantly directed against OspC (43%) and in a lower extent against the internal flagellin fragment and p100 (15% and 13%, respectively). The complete flagellin was not useful due to a high number of unspecific reactions with control sera and the OspA was only exceptionally reactive in Lyme borreliosis patients. The sensitivity of IgM antibody detection could be increased in cases with early Lyme borreliosis from 46% to 65% when the OspC blot was performed in addition to the flagellin ELISA, or from 56% to 65% when performed in addition to the OGP-ELISA. The recombinant blot is, therefore, a valuable diagnostic test to increase sensitivity of early antibody detection and is regarded as a valuable confirmatory test also in late disease.
Patients with Lyme borreliosis (LB) usually develop a vigorous T cell response against the causative pathogen Borrelia burgdorferi, but little is known about the antigens recognized in the cellular response. Therefore, T cell reactivities against whole bacteria, recombinant 31-kD (outer surface protein A, [OspA]), and 41-kD proteins (flagellin) from B. burgdorferi were studied in patients with LB, non-LB patients, and healthy donors. In parallel, specific antibodies were determined by Western blot analysis. Virtually all patients with LB exhibited marked cellular responses to whole B. burgdorferi, which were significantly elevated compared with the control groups in both early and late disease stages. However, analyses using the purified antigens OspA and flagellin revealed considerable heterogeneity in the cellular reactivities among individuals as well as variations during the course of infection. T cell responses to OspA were significantly increased in patients with early LB compared with both control groups whereas in late-stage disease responses only exceeded those of non-LB patients and were not different from normal donors. Cellular immune reactivities to flagellin were significantly higher only in early LB compared with both control groups. Reciprocally, several control subjects demonstrated marked cellular responses to OspA and flagellin, suggesting that reactions to these proteins may not always be related to LB. T cell reactivity did not correlate well with the presence of specific antibodies. Almost all seropositive patients in both early and late stage LB had serum antibodies against flagellin, but antibodies to OspA were detectable only in a subset of late LB sera. These data demonstrate the complexity of the humoral and the cellular immune responses to components of B. burgdorferi.
Arthritis of acute sarcoidosis or Löfgren's syndrome commonly affects the ankles. However, it is often difficult to determine by clinical means whether swelling of the ankles is due to frank arthritis or involvement of periarticular tissues. Therefore, sonographic examinations were performed in 24 consecutive patients with acute sarcoidosis, 16 of them with the typical triad of Löfgren's syndrome. Joint effusions could be demonstrated only by ultrasound in 6 patients. Sonographic findings consistent with tenosynovitis were found in 8 cases. In the majority of cases (20/24) the predominant abnormalities were hypoechogenic structures within the subcutis and periarticular tissues. Thus, frank arthritis is rather a rare cause of ankle swelling in Löfgren's syndrome; more often presumed joint manifestations can be attributed to subcutaneous or periarticular inflammation.
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Our clinical and serological studies have shown that Lyme arthritis is not a rare manifestation of Lyme borreliosis in Europe. The significance of serological findings for Lyme arthritis have more often remained uncertain in consideration of potential differential diagnoses than was to be expected on the basis of specificity controls. Various joint manifestations in the course of Lyme borreliosis have been distinguished. The succession or the coexistence of intermittent attacks of arthralgias and arthritis has been pointed out as particular indications of Lyme arthritis. We have noted diffuse hand and finger swelling as a striking feature of early Lyme arthritis. Generally, Lyme arthritis has been attributable to Stage 3 of the disease. The most pathognomonic manifestation has been intermittent knee arthritis. The pattern of joint involvement has shown similarities to that in postenteric and postveneral reactive arthritides, in particular as regards the occurence of dactylitis (sausage digits) and heel involvement. However, we have not seen sacroiliitis and Reiter's syndrome. As distinguished from typical Lyme arthritis, peculiar joint manifestations have been noted in association with acrodermatitis chronica atrophicans. Typing of Class I and II histocompatibility antigens did not give evidence of any immunogenetic basis for Lyme arthritis.
An expert system with 60 questions about medical history was developed for 32 rheumatologic diseases: 358 outpatients with joint complaints have been examined. The final diagnosis (result of symptoms, signs, and findings) was compared with the computer diagnoses and with the independently assumed diagnoses of the physician. The only source of information available to the physician was the medical history. Misinterpretation of the computer diagnoses occurred in 25.6% of cases compared with 21.5% of the physician. The final clinical diagnosis remained uncertain in 32.6% of cases. The error frequency of the expert system was influenced by the underlying disease, the certainty of the assumed diagnosis by the physician, the user experience in rheumatology, the number of questions asked, and the time of application before or after the doctor-patient contact. Of the errors 44% were produced because of information deficits of the computer using standardized questions. The information of the physician in the diagnostic process is quite different to that of the computer.
Prolyl 4-hydroxylase (EC 1.14.11.2) is a key enzyme required for the posttranslational hydroxylation of proline residues in collagen. The enzyme is a tetramer composed of two pairs of nonidentical subunits (alpha 2 beta 2). The beta subunit is protein disulfide-isomerase, a ubiquitous enzyme found in the endoplasmic reticulum of many cell types. We report here the amino acid sequence of the alpha subunit. One cDNA clone (alpha 1) was isolated from a chicken embryo cDNA expression library in lambda gt11 by screening with anti-alpha-subunit polyclonal immunoglobulins. This alpha 1 cDNA contains an open reading frame of 1401 base pairs. A comparison of the translation of the nucleotide sequence with protein sequences obtained from the purified chicken alpha-subunit polypeptide verified that alpha 1 cDNA encoded the alpha subunit. Polymerase chain reactions were used to extend the sequence of alpha 1 cDNA toward the 5' end of alpha-subunit mRNA. The mature alpha subunit is composed of 516 amino acids with a calculated molecular mass of 59,373 Da. The compiled amino acid sequence contains two potential glycosylation sites, an observation that agrees with a previous demonstration that the alpha subunit contains two N-linked oligosaccharide chains. Blot hybridization analysis of total chicken embryo RNA detected an mRNA of 3.5 kilobases, a size that closely resembles the size of the cloned cDNA. Since the expression of the alpha subunit is confined to cell types that synthesize and secrete collagens, the regulation of the synthesis of the alpha subunit may play a central role in determining the expression of prolyl 4-hydroxylase activity.
In a study on 121 consecutive patients with erythema migrans, 65 patients obtained oral penicillin, 36 tetracyclines, and 20 amoxicillin-clavulanic-acid. Follow-up was carried out for a median of 29, 17, and 7 months, respectively. In another limited trial on 29 patients with acrodermatitis chronica atrophicans (ACA), 14 patients received oral penicillin, 9 parenteral penicillin, and 6 tetracyclines. There was no statistically significant difference among treatment groups in both therapeutic trials, with the exception of different follow-ups due to the nonrandomized study design and different occurrence of the Jarisch-Herxheimer reaction in patients with erythema migrans. Later extracutaneous manifestations developed in 27% of the patients with erythema migrans and in 47% of the patients with ACA despite antibiotic therapy. We could not prove the superiority of any antibiotic tested in either early or late European Lyme borreliosis.
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Compared to American strains, European Borrelia burgdorferi strains revealed considerable heterogeneity of major proteins. Four strains isolated from ticks, human skin and human CSF were selected from our 23 Borrelia burgdorferi isolates. These strains and the American type strain B31 were characterized by SDS-PAGE (Coomassie Blue staining) and Western blots (using rabbit immune sera against two of the strains and two monoclonal antibodies (H5323 and H3TS) against a major outer surface protein (OspA]. The strains showed considerable differences in SDS-PAGE pattern. Corroborating the results of a previous study, we could demonstrate that the OspA (31/32K) can change from a minor to a major protein and in reverse the pC (21/22K) from a major to a minor protein during subculturing. Moreover, European strains can antigenically differ in OspA, pC and also in a further low molecular weight protein of 17/18K. To examine whether the antigenic heterogeneity of European isolates is reflected in the immune response of European patients we examined sera from patients with late manifestations of Lyme Borreliosis by Western blot using the five strains as antigens. Sera from seven patients with acrodermatitis chronica atrophicans (ACA) showed a surprisingly strong reactivity with the skin isolate. All sera had antibodies against the 17/18K protein of the skin isolate, but none was reactive with the analogous 17/18K of the other strains. On the other hand a comparable predominance of one strain was not found testing sera from patients with Lyme arthritis. One patient even had antibodies against OspA and OspB proteins of strain B31. Contrary to findings in American Lyme Disease antibodies against the OspA were rarely observed in the sera of our patients (only one patient had such antibodies) although we tested the patients sera with five different strains. Only two patients had stronger reactions with the skin isolate. These findings suggest that ACA is caused by antigenically closely related Borreliae. This could explain the finding that ACA is rarely observed in the US (US strains are antigenically closely related to strain B31). Our findings in patients with Lyme Arthritis--on the other hand--suggest that "different serotypes" can cause Lyme Arthritis. This does not exclude the possibility that Borrelia proteins are an important factor in the pathogenesis of Lyme arthritis. Finally the differences in reactivity of sera with different strains in the Western blot led us to examine whether such differences are also found in serodiagnostic tests using different strains as antigens.(ABSTRACT TRUNCATED AT 400 WORDS)