Giuseppe Passiu

Central nervous system involvement in systemic lupus erythematosus: cerebral imaging and serological profile in patients with and without overt neuropsychiatric manifestations

The aim of this study was to evaluate morphological and functional abnormalities by cerebral imaging in a series of systemic lupus erythematosus (SLE) patients with and without overt central nervous system (CNS) manifestations, and to detect possible relationships with clinical parameters and a large panel of autoantibodies, including those reactive against neurotypic and gliotypic antigens. 68 patients with SLE were investigated in a cross-sectional study which included clinical evaluation of symptoms, cerebral magnetic resonance imaging (MRI) and brain single photon emission tomography (SPECT) analysis, electroencephalography (EEG), and serological tests for antibodies directed against nuclear, cytoplasmic neuronal and glial cell-related antigens. The results of this study showed: (1) a significant positive association of (a) anti-glial fibrillary acidic protein (GFAP) serum antibodies with neuropsychiatric (NP) manifestations and (b) antiserin proteinase 3 (anti-PR3/c-ANCA) serum antibodies with pathological cerebral SPECT; (2) the presence of significantly higher values of (a) SLICC organ damage index in patients with abnormal MRI and (b) SLAM activity index in patients with abnormal SPECT; and (3) the association of (a) abnormal MRI with nonactive NP manifestations and (b) combined abnormality of brain SPECT and MRI with the occurrence of overall overt NP manifestations and with those of the organic/major type. Neuropsychiatric manifestations, namely those of the organic/major type, appeared to be significantly associated to the presence of a serum antibody against GFAP, a gliotypic antigen. There was also evidence of an association between SPECT abnormality and the presence of anti-PR3 (c-ANCA). Furthermore, brain imaging by MRI and SPECT applied to SLE patients appears to express CNS involvement significantly related to specific categories of NP manifestations. The abnormalities detected by the two tests seem to be preferentially associated with different activity phases of the NP disorder or of the lupus disease.

Effect of rituximab on clinical and laboratory features of antiphospholipid syndrome: a case report and a review of literature:

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by a hypercoagulable state related to persistently elevated levels of antiphospholipid antibodies (aPL). Current treatment for APS is only partially effective and new therapies are strongly needed. We report on a case of a 50 years old man with APS who suffered from recurrent thromboembolic episodes despite conventional anticoagulant treatment. Eight years after the first thrombotic manifestation he was diagnosed with a large B cell non-Hodgkin lymphoma. Treatment with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) plus rituximab was started with partial clinical remission of lymphoma and normalization of aPL levels with a three years follow-up period free of thrombotic episodes. A review of the literature revealed that only 12 case reports on the use of rituximab in patients with primary, secondary and catastrophic APS have been published. Current knowledge clearly suggests the need for clinical trials to evaluate the effect of rituximab in the treatment of resistant APS. Lupus (2008) 17, 50—55.

HLA-DPB1 alleles association of anticardiolipin and anti-beta2GPI antibodies in a large series of European patients with systemic lupus erythematosus.

Our objective was to determine the HLA-DPB1 allele associations of anticardiolipin (aCL) and anti-beta2 GPI (aβ2 GPI) antibodies, and of clinical manifestations of the antiphospholipid syndrome (APS), in systemic lupus erythematosus(SLE). We studied 577 European patients with SLE. aCL and aβ2 GPI antibodies were measured by ELISA. Molecular typing of HLA-DPB1 locus was performed by polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) method. aCL showed positive association with -DPB1*1501 (P 0.005, OR 7.4), and -DPB1*2301 (P 0.009, OR 3.3). aβ2 GPI showed positive association with -DPB1*0301 (P 0.01, OR 1.9), and -DPB1*1901 (P 0.004, OR 8.1). In addition, livedo reticularis was associated with -DPB1*1401, and Raynaud’s phenomenon with -DPB1*2001. In conclusion, HLA-DPB1 locus may contribute to the genetic predisposition to develop antiphospholipid antibodies and clinical manifestations of the APS in patients with SLE.

Abnormalities of magnetic resonance imaging of the central nervous system in patients with systemic lupus erythematosus correlate with disease severity

SummaryForty randomly selected patients with systemic lupus erythematosus (SLE) were studied by clinical and serologic parameters and magnetic resonance imaging (MRI). Abnormal MRI was found in 15/40 patients (37,5%): all 15 cases showed multiple widespread small-sized areas of increased signal in T2 in the white matter; in one of these patients MRI also displayed a large area with a reduced signal in T1 and an increased signal in T2 involving both the white and the gray matter. Among the 15 patients with abnormal MRI, only 7 had neuropsychiatric symptoms. The presence of MRI changes was highest in patients with organic type symptoms and was associated to the highest disease severity scores. A long-term follow up of asymptomatic patients would be useful to establish whether the application of MRI is appropriate for the assessment of CNS involvement in SLE.

Absence of epicardial coronary stenosis in patients with systemic sclerosis with severe impairment of coronary flow reserve

Systemic sclerosis (SSc) is known to be characterised by a diffuse microvascular pathological process leading to cutaneous and visceral changes and to related clinical manifestations. Both necropsy studies1,2 and in vivo investigations3–5 have shown that in a number of patients with SSc there is evidence of a coronary microvascular disease, while coronary artery disease does not exceed that seen in a control group. In particular, myocardial perfusion defects on thallium-201 scintigraphy usually occur in the absence of angiographic evidence of coronary stenosis.3 Recently, we used a new and non-invasive method of contrast enhanced, transthoracic, second harmonic echo Doppler in patients with SSc to evaluate the coronary flow reserve (CFR), a functional variable measuring the ability of the coronary microvasculature to adapt its lumen to a vasodilating stimulus.6 We detected a significant reduction of the CFR …

Bleomycin-induced scleroderma: Report of a case with a chronic course rather than the typical acute/subacute self-limiting form

Abstract: We report a case of bleomycin-induced scleroderma in a 35-year-old woman treated with chemotherapy for Hodgkin’s disease. Approximately 6 months after the first chemotherapy cycle, the patient developed skin sclerosis in both arms. The lesion showed no signs of spontaneous clinical amelioration and treatment with steroids was unsuccessful. A partial remission of the skin sclerosis was instead obtained by the administration of d-penicillamine. A family history revealed other cases of autoimmune diseases and HLA typing showed the presence of antigens associated with scleroderma. The association between bleomycin therapy and scleroderma is discussed.

Sustained normalization of cerebral blood-flow after iloprost therapy in a patient with neuropsychiatric systemic lupus erythematosus

We report the case of a 30-year-old caucasian woman affected by SLE who developed neurological symptoms (prosopagnosia and visual-spatial agnosia) after nine years of disease. Brain MRI showed no abnormalities while a brain SPECT scan showed diffuse uptake defects and hypoperfusion areas in the right and left frontal-parietal regions. At that time the patient was on hydroxychloroquine (400 mg/day) and oral prednisolone (0.5 mg/kg/day) as maintenance therapy. One year later the patient showed worsening of Raynauds phenomenon with digital dystrophic lesions and was therefore treated with an intravenous infusion of Iloprost (1.5 ng/kg/min per 6h/ day for 10 days consecutively), while baseline treatment remained unchanged. One month later the patient showed a dramatic improvement in her cognitive function and subsequent SPECT scans showed the gradual disappearance of perfusion abnormalities. This first report of Iloprost treatment in CNS lupus suggests the potential therapeutic usefulness of this drug in patients with SLE and functional CNS involvement.

Evaluation of cardiac functional abnormalities in systemic sclerosis by dobutamine stress echocardiography: a myocardial echostress scleroderma pattern.

In this study, we investigate the possibility of detecting, by dobutamine stress echocardiography (DSE), the presence of early or subclinical myocardial functional changes in patients with systemic sclerosis (SSc) without symptoms of ischaemic cardiac involvement.

Remitting asymmetrical pitting oedema in systemic lupus erythematosus: two cases studied with magnetic resonance imaging

To our knowledge, only three cases of remitting symmetrical pitting oedema in systemic lupus erythematosus have been reported so far. This is the first report of two patients with asymmetrical pitting oedema and systemic lupus erythematosus. The first patient presented two consecutive episodes of unilateral oedema. The first episode involved the distal part of the right lower extremity and remitted spontaneously while the second involved the volar region of the left wrist and distal half of the forearm and promptly responded to steroids. Magnetic resonance imaging of the left wrist and forearm showed tenosynovitis of the flexor tendons and subcutaneous oedema. The second patient instead developed a single episode of pitting oedema of the distal part of the right lower extremity that resolved spontaneously. Magnetic resonance imaging of the right ankle and foot showed subcutaneous oedema without involvement of the tendon sheaths or osteoarticular and ligamental structures. These two cases suggest that pitting oedema in systemic lupus erythematosus may occasionally be asymmetric and associated or not with tenosynovitis.

Increased pulmonary epithelial permeability in systemic sclerosis is associated with enhanced cutaneous nerve growth factor expression

Background: Nerve growth factor (NGF), a neurotrophic factor that indirectly induces fibroblast proliferation and collagen production, has been found to be increased in the affected dermis of patients with systemic sclerosis (SSc). To investigate the possibility of a relationship between cutaneous NGF production and pulmonary damage in SSc, we studied seven non-smoking scleroderma patients. Methods: Abnormalities in lung structure were assessed by radiological lung examination, and pulmonary epithelial permeability (PEP) was determined by ventilation lung scintigraphy. All patients underwent skin punch biopsy with NGF immunohistological staining. Results: A statistically significant correlation was found between the PEP values and the cutaneous NGF staining scores, which were markedly increased in all of the patients examined, irrespective of the age, disease duration, or radiologically defined lung abnormalities. Conclusion: These results support the hypothesis that functional and anatomical changes in SSc target organs may be determined by a local tissue hyperproduction of NGF.