No difference in the incidences of vasculitides between north and south Germany: first results of the German vasculitis register.

OBJECTIVE: To register all newly diagnosed patients with primary systemic vasculitis (PSV) in two large regions in north and south Germany. METHODS: Between 1 January 1998 and 31 December 1999, all newly diagnosed cases of PSV, as defined by the Chapel Hill Consensus Conference 1992, were identified in two large mixed rural/urban regions in north and south Germany with a combined population of 4,880,543, for a population-based prospective study. The following sources were used: (i) all departments of every hospital, including their out-patient clinics; (ii) all departments of pathology; and (iii) all reference immunological laboratories serving the catchment area. All cases were re-evaluated by the authors. RESULTS: Over the whole period, 473 individuals were registered as having a new PSV. The incidence rates for all PSV were 54 cases per 1,000,000 inhabitants in the north and 48 in the south in 1998, and 48 and 41 respectively in 1999. People 50 yr and older had a three- to five-fold higher risk of getting PSVs than those under 50 yr. The incidences of antineutrophil cytoplasmic antibody (ANCA)-associated PSVs [Wegener's granulomatosis (WG), microscopic polyangiitis (MPA) and Churg-Strauss syndrome (CSS)] remained stable in both regions, at about 9.5 per 1,000,000 annually. The incidence of WG was two to three times greater than those of MPA and CSS. There was no difference in incidence rates between north and south Germany. CONCLUSION: First results from a population-based vasculitis register serving nearly 5,000,000 inhabitants in north and south Germany revealed no regional differences in the incidence of all PSVs between north and south. The incidence rates of ANCA-associated PSVs, such as WG and MPA, were lower than those in the UK and Norway but higher than that in Spain.

Diagnosis and monitoring of central nervous system involvement in systemic lupus erythematosus: value of F-18 fluorodeoxyglucose PET.

OBJECTIVE: To investigate prospectively abnormalities of brain glucose utilisation in relation to major or minor neuropsychiatric symptoms in systemic lupus erythematosus (SLE). METHODS: Positron emission tomography (PET) using F-18-labelled fluorodeoxyglucose was performed in 28 patients with SLE. Patients were classified as having severe neuropsychiatric manifestations (seizures, focal neurological deficits, acute confusional states, mood disorders) (n=12), or mild neuropsychiatric manifestations (headache, reactive depression, cognitive dysfunction, anxiety disorders) (n=11) and five patients without signs of central nervous system (CNS) involvement. Ten clinically and neurologically healthy volunteers served as controls. In 26 patients magnetic resonance imaging (MRI) was performed and autoantibodies against CNS tissue, ribosomal P protein and cardiolipin were measured. In 14 patients follow up PET scans were performed after a mean (SD) period of 11.6 (9.5) months. RESULTS: PET scans showed hypometabolism in at least one brain region in all patients with severe or mild CNS symptoms (100%) as compared with patients without cerebral symptoms (40%) (p<0.0025). Parieto-occipital regions were most commonly affected (96%), followed by parietal regions (32%). In contrast, MRI images were abnormal in only 11 of 22 patients (50%) with neuropsychiatric symptoms and in one of four patients (25%) without symptoms. In 12 of 14 patients examined in follow up PET scans persistence, improvement or worsening of cerebral symptoms were associated with unchanged, decreased or increased brain hypometabolism, respectively. No significant correlation was found between PET or MRI findings and autoantibody profiles. CONCLUSIONS: PET imaging represents a sensitive tool to detect manifest or subclinical CNS involvement in SLE and PET findings correlate well with the clinical course of disease.

Giant cell arteritis is more prevalent in urban than in rural populations: results of an epidemiological study of primary systemic vasculitides in Germany.

OBJECTIVE: To investigate the period prevalences of primary systemic vasculitides (PSV) in urban and rural populations in northern and southern Germany in 1994. METHODS: Questionnaires were sent to all hospital departments, all physicians, health insurance providers and pension funds, reference laboratories for autoimmune diseases, and death registries in two catchment areas in northern and southern Germany (combined population 875 983) to identify patients with PSV between 1 January and 31 December 1994. Each catchment area encompassed both an urban and a rural area. Each case was re-evaluated by the authors by applying the definitions of the 1992 Chapel Hill Consensus Conference on the Nomenclature of Systemic Vasculitis. RESULTS: A total of 180 PSV patients were identified. The overall prevalence of PSV was 216 cases per 1 000 000 inhabitants (95% confidence interval (CI) 173-259) in northern Germany vs 195 (95% CI 153-236) in southern Germany. The prevalence of PSV was two-fold higher in women than in men, and five-fold higher in people aged > or =50 yr than in people aged <50 yr. The most frequent type of PSV was giant cell arteritis (GCA), with 87 cases per 1 000 000 in northern and 94 in southern Germany, followed by Wegener's granulomatosis, with 58 and 42 cases respectively. In the population aged > or =50 yr the prevalence of GCA was 240 per 1 000 000 in northern and 300 in southern Germany. In both northern and southern Germany the prevalence of GCA in this older population was significantly higher in urban than in rural populations (355 per 1 000 000 vs 115 in northern Germany (P<0.01) and 395 vs 220 (P<0.05) in southern Germany). The relative risk for the older urban population having GCA was 2.25-fold higher (95% CI 1.4-3.6) than in the rural population, and for the female population it was 4.7-fold higher in the urban than in the rural areas (95% CI 2.4-9.3). CONCLUSION: In both northern and southern Germany, GCA was significantly more prevalent in urban than in rural populations, especially among people aged > or =50 yr and in women. It remains unclear whether this disparity was due to underdiagnosis of GCA in the rural regions associated with differences in the German health-care system in cities vs rural areas. Further studies must examine the role of (chronic) exposure to the environmental factors characteristic of cities.

Diagnosis of idiopathic myositis: value of 99mtechnetium pyrophosphate muscle scintigraphy and magnetic resonance imaging in targeted muscle biopsy.

Our objective was to study the value of 99mtechnetium-pyrophosphate (99mTc-PYP) muscle scintigraphy and magnetic resonance imaging (MRI) in detecting areas of likely muscle inflammation and in increasing the rate of positive muscle biopsies in patients with suspected myositis. The results showed that in 13 out of 13 patients with clinical and/or signs of inflammatory muscle disease, increased 99mTc-PYP uptake was demonstrated at different muscle sites 3 h after isotope injection. Subsequent MRI of symmetric muscle areas with enhanced 99mTc-PYP uptake revealed signal patterns suggesting inflammation in all cases. Biopsy of these targeted muscles demonstrated characteristic histopathologic signs of muscle inflammation in 9 out of 13 patients. Four of these 9 patients had clinically atypical disease or did not show elevated creatine phosphokinase levels. Seven of these 9 patients had not been pretreated with corticosteroids. In 4 patients only muscle fiber atrophy and/or necrosis without cellular infiltrations was seen. These 4 patients had received either high doses of corticosteroids or low doses over longer periods of time before muscle biopsy. In conclusion, the combination of 99mTc-PYP muscle scintigraphy and MRI demonstrated muscle areas with maximum inflammatory signal patterns. Targeting of muscles by MRI only will probably yield reliable results of muscle biopsy in cases of clinically and serologically characteristic myositis. 99mTc-PYP muscle scintigraphy may provide useful initial information about localization of inflamed muscle tissue, especially in atypical disease. Treatment with corticosteroids prior to histologic diagnosis may abolish inflammatory infiltrations in affected muscle tissue.

Brain glucose utilization in systemic lupus erythematosus with neuropsychiatric symptoms: a controlled positron emission tomography study.

In contrast to morphological imaging [such as magnetic resonance imaging (MRI) or computed tomography], functional imaging may be of advantage in the detection of brain abnormalities in cases of neuropsychiatric systemic lupus erythematosus (SLE). Therefore, we studied 13 patients (aged 40+/-14 years, 11 female, 2 male) with neuropsychiatric SLE who met four of the American Rheumatism Association criteria for the classification of SLE. Ten clinically and neurologically healthy volunteers served as controls (aged 40+/-12 years, 5 female, 5 male). Both groups were investigated using fluorine-18-labelled fluorodeoxyglucose brain positron emission tomography (PET) and cranial MRI. The normal controls and 11 of the 13 patients showed normal MRI scans. However, PET scan was abnormal in all 13 SLE patients. Significant group-to-group differences in the glucose metabolic index (GMI=region of interest uptake/global uptake at the level of the basal ganglia and thalamus) were found in the parieto-occipital region on both sides: the GMI of the parieto-occipital region on the right side was 0.922+/-0.045 in patients and 1.066+/-0.081 in controls (P<<0.0001, Mann Whitney U test), while on the left side it was 0.892+/-0.060 in patients and 1. 034+/-0.051 in controls (P=0.0002). Parieto-occipital hypometabolism is a conspicuous finding in mainly MRI-negative neuropsychiatric SLE. As the parieto-occipital region is located at the boundary of blood supply of all three major arteries, it could be the most vulnerable zone of the cerebrum and may be affected at an early stage of the cerebrovascular disease.

Multicentric reticulohistiocytosis. A report of 3 cases and review of literature.

Multicentric reticulohistiocytosis (MR) is a rare systemic disease of unknown cause. The disease is characterized by tissue infiltration of lipid-laden histiocytes and multinucleated giant cells. Destructive polyarthritis and skin lesions are the most common findings. The disease becomes apparent in adult life. We report on 3 patients and discuss the specific radiographic characteristics of bone and joint involvement. The radiologic feature is a bilateral, symmetric joint involvement with predilection for the interphalangeal and metacarpophalangeal joints. In all of our cases we found an early involvement of shoulder joints. Erosive arthritis begins at the margins of the joints, progressing to osseous defects and to severe joint destruction. In contrast to rheumatoid arthritis, periarticular osteoporosis and early joint space loss are absent in MR. In addition, significant erosions of distal interphalangeal joints are not common in rheumatoid arthritis.

Activated CD4+ and CD8+ T-cell subsets in Wegener's granulomatosis.

Several lines of evidence argue in favour of an involvement of T cells in the pathogenesis of Wegener's granulomatosis (WG). These include the presence of highly specific IgG autoantibodies to proteinase 3, perivascular T-cell infiltrates and elevated amounts of soluble interleukin-2 (IL-2) receptors in patient's serum. In order to further address this question we evaluated by double immunofluorescence and flow cytometry the expression of several cell surface molecules associated with T-cell activation. As compared to healthy controls (n = 15), the CD4+ subset was significantly diminished, while the percentage of CD8+ T cells was elevated in WG patients (n = 24). Within the CD4+ T-cell subset we found a highly significant increase in activation/memory markers (CD25, CD29, HLA-DR). Within the CD8+ T-cell subset the expression of CD11b, CD29 and CD57 was significantly elevated, while the expression of VD28 was reduced. The use of 10 V beta-, 1 V alpha- and 1 V gamma-specific monoclonal reagents failed to reveal any significant bias in the peripheral T-cell receptor V-gene repertoire of WG patients. There was also no correlation between T-cell activation markers and laboratory parameters [C-reactive protein (CRP), ESR], disease duration or therapy. A significant correlation was found only for the degree of organ involvement and the increase in CD4+ T cells coexpressing HLA-DR, as well as the increase in CD57 expression on CD8+ T cells. In conclusion, both CD4+ and CD8+ T-cell subsets were activated in WG. Cytotoxic CD8+CD57+CD11b+CD28- T cells may directly contribute to damage of vascular endothelium.

Impaired granulocyte oxidative burst and decreased expression of leucocyte adhesion molecule-1 (LAM-1) in patients with Wegener's granulomatosis.

Neutrophils are the target of autoantibodies in Wegener's granulomatosis (WG). In this study, granulocyte function and surface marker expression were investigated in patients with WG. The oxidative burst in response to phorbol myristate acetate (PMA) was tested with granulocytes of 25 patients with histologically proven WG. A significantly diminished percentage of oxygen radical-producing cells was found in patients with active disease. Surface antigen expression of CD11b and LAM-1 was analysed on granulocytes of 20 patients with WG. Whereas the expression of CD11b was normal, surface expression of LAM-1 was decreased in nine cases with WG. The decrease of LAM-1 correlated with disease activity. Phagocytosis of Escherichia coli was tested in 10 patients with WG, and normal values were found in all cases. We conclude that down-regulation of LAM-1 may be a marker of disease activity in WG. The altered response to PMA may indicate functional changes in granulocyte reactivity due to autoantibody-induced damage of the granulocyte membrane.

Increased expression of CD25 and adhesion molecules on peripheral blood lymphocytes of patients with Wegener's granulomatosis (WG) and ANCA positive vasculitides.

Peripheral blood lymphocytes of 29 c-ANCA positive WG patients fulfilling the ACR classification criteria were examined for the expression of various leukocyte surface molecules by dual marker cytofluorometry (FACStar, Becton Dickinson). Activation markers such as CD25, HLA-DR, CD29 and adhesion molecules (ICAM-1 and LFA-3) were clearly elevated in this group in comparison to 40 healthy volunteers. Similar results were obtained for p-ANCA positives vasculitides (n = 13) and, unexpectedly, also for patients suffering from cholesteatoma, a chronic, bacterial infection of the middle ear (n = 21). The results are discussed in view of a pathogenic model for WG and vasculitic disorders.

Model system for studying colonization and growth of bacteria on a hydroxyapatite surface.

A model system for the study of bacterial colonization and growth on a hydroxyapatite (HT) surface is described. Hydroxyapatite was crystallized over the surface of porous glass beads. Chemical analysis of the product showed that the ratio of Ca2+/P042- was indistinguishable from that of commercial HT powder. X-ray diffraction analysis supported the conclusion that the product was HT. A system employing [14C]polyethylene glycol, which selectively adsorbs to the glass surface of the beads, was developed to determine the amount of glass surface covered by HT. Over 90% of the glass surface could be covered by our method. The product, HT beads, consisted of approximately 20% (dry weight) HT. The HT beads possess several properties which make them potentially useful for studying microbial adherence, growth, and interactions. These include: (i) chemical similarity to the tooth surface, (ii) large surface area, and (iii) high density. We also describe a method for direct measurement of the microbial mass of cells growing on beads. The method entails immobilizing a sample on a membrane filter (Millipore), staining it with amido black dye, and eluting the dye for spectrophotometric measurement. Streptococcus mutans served as the test organism. For free-growing bacteria the values measured with the filter assay were directly proportional to cell number, with a value of 1 mug of "protein" corresponding to about 1.5 X 10(6) colony-forming units, determined by viable count. For bacteria colonizing the beads, 1 mug of protein corresponded to about 2 X 10(7) colony-forming units on the beads during logarithmic growth. As the culture approached stationary phase, the efficiency of the assay decreased. These data indicate that multiple random samples, taken at a given time, are representative of the entire culture.