An approach to diagnosis and initial management of systemic vasculitis.
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Systemic vasculitis occurs in a heterogeneous group of primary disorders or can be a manifestation of infection, an adverse drug reaction, malignancy or a connective tissue disease. A vasculitic process should be suspected in patients with unexplained ischemia or multiple organ involvement, especially when such features as polymyalgia rheumatica, inflammatory arthritis, palpable purpura, glomerulonephritis or multiple mononeuropathy are also present. The clinical features of systemic vasculitis depend on the organs involved and, in turn, organ involvement is largely influenced by the size of the affected blood vessels. The diagnostic work-up should be tailored to the clinical situation and geared toward a tissue or angiographic diagnosis, bearing in mind that the findings from these studies are not always pathognomonic. Emphasis should also be placed on exclusion of a secondary process. The diagnosis of the specific type of vasculitis may be made on the basis of the clinical features and the histopathologic or angiographic findings. Initial therapy for most types of systemic vasculitis consists of high-dose corticosteroids, with the addition of immunosuppressive therapy in certain patients. (+info)
Immunopathology of ANCA-associated vasculitis.
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During the past few years remarkable progress has been achieved in the understanding of the pathogenic mechanisms leading to vascular inflammation and injury in ANCA-associated vasulitides (AAV): Wegener's granulomatosis (WG), microscopic polyangiitis (MPA) and Churg Strauss syndrome (CSS). In this paper we review the immunopathology of these diseases by describing the role of autoantibodies (ANCA), dysregulation and abnormalities at the cellular level, genetic background and environmental factors that predispose to autoimmune response. (+info)
An evaluation of the Banff classification of early renal allograft biopsies and correlation with outcome.
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BACKGROUND: The Banff classification for assessment of renal allograft biopsies was introduced as a standardized international classification of renal allograft pathology and acute rejection. Subsequent debate and evaluation studies have attempted to develop and refine the classification. A recent alternative classification, known as the National Institutes of Health Collaborative Clinical Trials in Transplantation (NIH-CCTT) classification, proposed three distinct types of acute rejection. The 1997 Fourth Banff meeting appeared to move towards a consensus for describing transplant biopsies, which incorporated both approaches. Patients who received a renal allograft at the Oxford Transplant Centre were managed by a combination of protocol and clinically indicated biopsies. We have undertaken a retrospective analysis of the biopsies correlated with the clinical outcome to test the prognostic value of the original Banff (Banff 93-95) and NIH-CCTT classifications. METHODS: Three hundred and eighty-two patients received renal allografts between May 1985 and December 1989, and were immunosuppressed using a standard protocol of cyclosporine, azathioprine and steroid. Adequate 5-year follow-up data were available on 351 patients, and of these, 293 had at least one satisfactory biopsy taken between days 2 and 35 after transplantation, the latter patients forming the study group. The D2-35 biopsies taken from these patients, which were not originally reported according to the Banff classification, were re-examined and classified according to the Banff 93-95 protocols. For each patient the biopsy found to be the most severely abnormal was selected, and the Banff and NIH-CCTT grading compared with the clinical outcome. RESULTS: Seven hundred and forty-three biopsies taken from 293 patients between days 2 and 35 after transplantation were examined and the patients categorized on the basis of the 'worst' Banff grading as follows. Normal or non-rejection, 20%; borderline, 34%; acute rejection grade I (AR I), 18%; AR IIA, 6%; AR IIB, 14%; AR III, 1%; AR IIIC, 3%; widespread necrosis 3%. The clinical outcome for the last two groups combined was very poor with 18% of grafts functioning at 3 months and 6% at 5 years. The other groups with vascular rejection (AR IIB and AR III) had an intermediate outcome, graft survival being 78% at 3 months and 61% at 5 years. The remaining four groups (normal, borderline, cellular AR I and AR IIA) had the best outcome: graft survival 95% at 3 months and 78% at 5 years with virtually no difference between the four groups. Three forms of acute rejection, namely tubulo-interstitial, vascular and transmural vascular, were identified, but only the latter two categories were associated with a poor outcome. CONCLUSIONS: The eight sub-categories of the Banff classification of renal allograft biopsies are associated with three different prognoses with respect to graft survival in the medium term. These three prognostic groups correspond to the three NIH-CCTT types. The data provide support for the consensus developed at Banff 97 separating tubulo-interstitial, vascular and transmural vascular rejection (types I, II and III acute rejection). (+info)
Rheumatic disorders developed after hepatitis B vaccination.
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OBJECTIVE: To obtain an overview of rheumatic disorders occurring after hepatitis B vaccination. METHODS: A questionnaire was sent to rheumatology departments in nine French hospitals. Criteria for entry were rheumatic complaints of 1 week's duration or more, occurrence during the 2 months following hepatitis B vaccination, no previously diagnosed rheumatic disease and no other explanation for the complaints. RESULTS: Twenty-two patients were included. The observed disorders were as follows: rheumatoid arthritis for six patients; exacerbation of a previously non-diagnosed systemic lupus erythematosus for two; post-vaccinal arthritis for five; polyarthralgia-myalgia for four; suspected or biopsy-proved vasculitis for three; miscellaneous for two. CONCLUSIONS: Hepatitis B vaccine might be followed by various rheumatic conditions and might trigger the onset of underlying inflammatory or autoimmune rheumatic diseases. However, a causal relationship between hepatitis B vaccination and the observed rheumatic manifestations cannot be easily established. Further epidemiological studies are needed to establish whether hepatitis B vaccination is associated or not with an incidence of rheumatic disorders higher than normal. (+info)
The activation of the neutrophil respiratory burst by anti-neutrophil cytoplasm autoantibody (ANCA) from patients with systemic vasculitis requires tyrosine kinases and protein kinase C activation.
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The ability of antineutrophil cytoplasm autoantibodies (ANCA) from patients with systemic vasculitis to stimulate protein kinase C (PKC) and tyrosine kinases was examined in human neutrophils. Using the superoxide dismutase-inhibitable reduction of ferricytochrome C, the kinetics of ANCA-induced superoxide (O2-) production were characterized and subsequently manipulated by specific inhibitors of PKC and tyrosine kinases. With this approach, ANCA IgG, but not normal IgG or ANCA F(ab')2 fragments caused a time and dose dependent release of O2- from TNF-alpha primed neutrophils. The kinetics of ANCA-induced O2- production showed an initial 10-15 min lag phase compared to the N-formyl-L-methionyl-L-leucyl-L-phenylalanine response, suggesting differences in the signalling pathways recruited by these two stimuli. Inhibitor studies revealed that ANCA-activation involved members of both the Ca2+-dependent and -independent PKC isoforms and also tyrosine kinases. ANCA IgG resulted in the translocation of the betaII isoform of PKC at a time corresponding to the end of the lag phase of O2- production, suggesting that PKC activity may be instrumental in processes regulating the activity of the NADPH oxidase in response to ANCA. Tyrosine phosphorylation of numerous proteins also peaked 10-15 min after stimulation with ANCA but not normal IgG. These data suggest that PKC and tyrosine kinases regulate O2- production from neutrophils stimulated with autoantibodies from patients with systemic vasculitis. (+info)
Validity of a vasculitis activity index for systemic necrotizing vasculitis.
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OBJECTIVE: To establish the validity of an index designed to measure activity in systemic necrotizing vasculitis (SNV). METHODS: The Vasculitis Activity Index (VAI) was designed to incorporate appropriately weighted clinical measurements that reflect disease activity in SNV. We performed a pilot study to guide the modification and subsequent testing of the initial design. The data necessary to calculate the VAI are direct ratings by a clinical observer of the degree of activity in 9 organ systems and 3 indirect measures of vasculitis activity. These data are recorded on 0-4 visual analog scales. Physician's global assessment (PGA) is used as the "gold standard" measurement of disease activity. The VAI was validated using 2 independent data sets: the questionnaire data set, derived from test case histories ("paper cases") sent to 100 practicing rheumatologists, and the clinic data set, obtained from use of the VAI in 204 regular care visits of 74 patients with SNV. RESULTS: The VAI correlated highly with the PGA: Pearson's correlation coefficient R = 0.84 (95% confidence interval [95% CI] 0.80-0.88) for the questionnaire data set, and R = 0.92 (95% CI 0.90-0.94) for the clinic data set. The mean of the interobserver coefficients of variation for the test case histories was lower for the VAI than for the PGA (mean difference 0.45; P = 0.002), indicating that the VAI has less interobserver variation than does the PGA. The change in VAI between clinic visits for individual patients correlated highly with the change in PGA (R = 0.88, 95% CI = 0.83-0.91). The VAI data collection form requires about 1 minute to complete, including computation of the score. CONCLUSION: The VAI is a valid measure of vasculitis activity that correlates highly with the PGA. In addition, the VAI has less interobserver variation than the PGA and has a high level of sensitivity to change over time. Additional testing of the VAI appears warranted. (+info)
Endothelial nuclear factor-kappaB translocation and vascular cell adhesion molecule-1 induction by complement: inhibition with anti-human C5 therapy or cGMP analogues.
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We have previously shown that reoxygenation of hypoxic human umbilical vein endothelial cells (HUVECs) leads to the activation and deposition of complement. In the present study, we investigated whether the terminal complement complex (C5b-9) influences HUVEC nuclear factor-kappaB (NF-kappaB) translocation and vascular cell adhesion molecule-1 (VCAM-1) protein expression after hypoxia/reoxygenation by decreasing endothelial cGMP. Additionally, we investigated the action of anti-human C5 therapy on endothelial cGMP, NF-kappaB translocation, and VCAM-1 protein expression. Reoxygenation (0.5 to 3 hours, 21% O(2)) of hypoxic (12 hours, 1% O(2)) HUVECs in human serum (HS) significantly increased C5b-9 deposition, VCAM-1 expression, and NF-kappaB translocation compared with hypoxic/reoxygenated HUVECs treated with the recombinant human C5 inhibitor h5G1.1-scFv. Acetylcholine (ACh)-induced cGMP synthesis was significantly higher in normoxic HUVECs compared with hypoxic HUVECs reoxygenated in HS but did not differ from hypoxic HUVECs reoxygenated in buffer or HS treated with h5G1.1-scFv. Treatment of hypoxic/reoxygenated HUVECs with h5G1.1-scFv or cGMP analogues significantly attenuated NF-kappaB translocation and VCAM-1 protein expression. Treatment with NO analogues, but not a cAMP analogue, cGMP antagonists, or an NO antagonist, also significantly attenuated VCAM-1 expression. We conclude that (1) C5b-9 deposition, NF-kappaB translocation, and VCAM-1 protein expression are increased in hypoxic HUVECs reoxygenated in HS; (2) reoxygenation of hypoxic HUVECs in HS, but not buffer alone, attenuates ACh-induced cGMP synthesis; and (3) treatment of hypoxic/reoxygenated HUVECs with h5G1.1-scFv attenuates C5b-9 deposition, NF-kappaB translocation, and VCAM-1 expression while preserving ACh-induced cGMP synthesis. C5b-9-induced VCAM-1 expression may thus involve an NO/cGMP-regulated NF-kappaB translocation mechanism. (+info)
Systemic vasculitis and aneurysm formation in the Wiskott-Aldrich syndrome.
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A 24 year old male who suffered from the Wiskott-Aldrich syndrome developed intra-abdominal bleeding on two occasions. Radiological investigations showed aneurysmal dilatation of branches of the hepatic and superior mesenteric arteries. The second abdominal bleed necessitated laparotomy and the bleeding was localised to the kidneys. Right nephrectomy was performed and histological examination showed a necrotising vasculitis, mainly involving medium and small sized renal blood vessels. Steroids, immunosuppressive treatment, and control of blood pressure resulted in resolution of the vasculitic process and prevented further haemorrhage. Vasculitis and aneurysm formation are rarely described complications of Wiskott-Aldrich syndrome and may account for the life threatening haemorrhage which occurs in this condition. (+info)