Lombardi A

Neutral endopeptidase (3.4.24.11) in plasma and synovial fluid of patients with rheumatoid arthritis. A marker of disease activity or a regulator of pain and inflammation

SummaryIn recent years the role of the peripheral nervous system has been focused on the pathogenesis of rheumatoid arthritis (RA). In particular, substance P (SP), released by the sensory terminals, has been demonstrated to be involved in cartilage breakdown [13]. The aim of our work was to study the levels of SP and its peptidases, neutral endopeptidase (3.4.24.11) (NEP) and angiotensin-converting enzyme (ACE), in the synovial fluid and plasma of 30 patients with RA and 14 patients with osteoarthritis (OA). ACE and NEP were determined with a fluorimetric assay and SP with a radioimmunoassay (RIA) method. ACE levels were normal in the plasma of patients with RA and OA (6.1±1.9 and 6.7±1.4 pmol/ml/min, respectively); we found no differences in the values, of ACE between RA and OA synovial fluid (5.7±4.2 and 5.5±4.1 pmol/ml/min, respectively). NEP levels were significantly increased in plasma (139.3±36 pmol/ml/min) and synovial fluid (133.8±32 pmol/ml/min in synovial fluid) and healthy controls (89.7±14 pmol/ml/min in plasma). In synovial fluid, SP was significantly higher in RA patients (43.1±16.6 pg/ ml) than in OA patients (12±13.1 pg/ml), while plasma levels did not show any difference (RA: 14.4±10.2; OA: 13.6±10.6; healthy subjects: 11.3±3.9 pg/ml). The only relationship detected in controls and in OA was among plasma NEP and ESR (P<0.05) and synovial fluid NEP (P<0.001). Our data confirmed that SP could have a role in the pathogenesis of RA synovial inflammation through a control on neurogenic inflammation (SP degradation), vascular tone control (endothelin degradation) and on nociception (enkephalin degradation).

High resolution computed tomography in systemic sclerosis. Real diagnostic utilities in the assessment of pulmonary involvement and comparison with other modalities of lung investigation

SummaryThe real utility of high resolution computed tomography (HRCT) for early detection of lung involvement was investigated in eighteen patients affected with systemic sclerosis (SSc). The results obtained from HRCT have been compared with traditional (chest radiographs, pulmonary function tests (PFT)) and nontraditional (ventilation and perfusion scintiscan) modalities of lung investigation. A significant statistical correlation (p<0.001) between HRCT scans and chest radiographs was observed. Moreover, HRCT was more sensitive in the detection of early pulmonary interstitial involvement and more accurate in the assessment of interstitial fibrosis in cases with severe lung involvement. A statistical correlation (P<0.001) between HRCT and the modalities of investigation of alveolo-capillary membrane — as PFT and ventilation scintiscan — was also observed. These results indicate that in SSc HRCT may be a useful technique for assessing early pulmonary involvement and for complementing other methodologies of investigation of lung function.

Colchicine treatment in a case of pachydermoperiostosis with acroosteolysis

SummaryWe report a case of pachydermoperiostosis with arthralgia, acroosteolysis, and recurrent staphilococcal folliculitis of the face, treated with colchicine (0.5 mg once daily for the 1st week and 0.5 mg twice daily for the next 3 weeks). The evaluation of arthralgia, hyponchial angle, folliculitis, and pachyderma, performed at basal time and once weekly, showed improvement of symptoms and signs after 7–15 days of treatment. Neutrophilic chemotaxis, evaluated before starting the treatment and after 15 and 30 days of therapy, showed a progressive decrease of the initial very high index. Colchicine provided a beneficial therapeutic response in both inhibiting increased chemotactic activity and in reducing tissular oedema in our patient.

Cutaneous and Plasma Fibrinolytic Activity in Systemic Sclerosis.: Evidence of Normal Plasminogen Activation

Abstract: Eleven patients with systemic sclerosis (SSc) were studied for plasma and cutaneous fibrinolytic activity, residual (potential fibrinolysis) fibrinolytic activity (FA) of the dermal vessels that is related to the endothelial storage of plasminogen activators that become available due to particular stimuli such as intradermic injection of histamine, and the serum levels of circulating von Willebrand antigen, antithrombin III, plasminogen, (β‐thromboglobulin, and platelet aggregate ratio (PAR). Cutaneous FA (autohistographic fibrin film method) appeared normal or increased in non‐affected skin, normal in lesional skin, and increased after intradermal (i.d.) injection of 0.1 ml of 0.01% histamine. Monoclonal antibodies directed against the catalytic site of tissue type plasminogen activator completely blocked the fibrinolytic activity, while anti‐urokinase antibodies did not abolish the lysis areas. Plasmatic FA, euglobulin lysis time test, (ELT) and the levels of β‐thromboglobulin resulted similar to the controls. A significant increase in von Willebrand Factor VIII antigen (but not of Factor VIII coagulant) was observed in the patients (p < 0.01). Platelet aggregate ratio, levels of plasma plasminogen and Antithrombin III showed a significant difference (p < 0.01) when compared with the control subjects. Data suggest that primary injured microvessels in SSc are likely to be arteriolae while venulae could be affected by secondary hypoxia due to the arteriolar damage with consequent release of tissue type plasminogen activator. Therefore, the authors suggest that the fibrinolytic potential is maintained in SSc and that the fibrinolytic therapy should not be used in all patients with SSc but only in those cases with documented exhaustion of plasmatic and/or cutaneous FA.

Suppression of autoantibodies to factor VIII and correction of factor VIII deficiency with a combined steroid-cyclophosphamide-porcine factor VIII treatment in a patient with rheumatoid arthritis

Abstract. The presence of autoantibodies against factor VIII is an unusual but serious complication in rheumatoid arthritis. We describe the case of a patient who developed this kind of complication, with spontaneous bleeding and marked changes in the haematological parameters, that was unsuccessfully treated with a high dose of intravenous gammaglobulin. Subsequently, combined therapy with porcine factor VIII concentrate, cyclophosphamide and steroids led to the disappearance of the anti‐factor VIII autoantibodies.