Evaluation of the influence of social, demographic, environmental, work-related factors and/or lifestyle habits on Raynaud's phenomenon: a case-control study.

Raynaud's phenomenon (RP) is a clinical disorder characterized by recurrent, reversible episodes of digital vasospasm. RP can be classified as primary (pRP) or secondary, depending on whether it occurs as a benign condition (not disease-associated) or is associated with other diseases, mainly of the connective tissues. In both cases, it can be triggered by environmental factors, as indicated by the increased incidence of pRP episodes following exposure to cold, vibration injury or chemicals. The purpose of this prospective case-control study was to assess, in an Italian cohort of 132 pRP patients, the association of the phenomenon with demographic, lifestyle habits, environmental and work-related factors. Compared to healthy controls, pRP was found to be inversely associated with the use of contact lenses (OR = 0.4; p = 0.004) and of chlorous-based disinfectants (OR = 0.3; p < 0.001) and directly associated with the presence of prosthesis implants (OR = 5.3; p = 0.001) and the use of hydrogen peroxide-based compounds (OR = 2.6; p = 0.002), suggesting that the latter should be avoided in RP affected patients. Multivariate and multivariable analysis confirmed the associations. Further investigations are needed to understand the mechanism(s) underlying these findings.

Pathogenesis and potential therapeutic targets in systemic lupus erythematosus: from bench to bedside.

Systemic lupus erythematosus (SLE) is considered an autoimmune disease with multiorgan involvement. Many advances have been made during the last decade regarding inflammatory pathways, genetic and epigenetic alterations, adaptive and innate immune system mechanisms specifically involved in SLE pathogenesis. Apoptosis has been proposed as an important player in SLE pathogenesis more than a decade ago. However, only recently new key apoptotic pathways have been investigated and the link between apoptotic debris containing autoantigens, innate immunity and ongoing inflammation has been further elucidated. Better understanding of cellular mechanisms and involved cytokines contributed to the development of new biological drugs specifically addressed for SLE therapy.

Systemic lupus erythematosus: immunopathogenesis and novel therapeutic targets.

Systemic lupus erythematosus (SLE) is the prototype of autoimmune diseases with multiorgan involvement. SLE presents many genetic and epigenetic associations and the pathogenesis is characterized by a complex network of alterations affecting both adaptative and innate immunity. The disclosure of novel mechanisms of SLE pathogenesis suggested new therapeutic targets, based on interference with the cytokine pathways or on depletion of the immune cells.

Arterial occlusion mimicking vasculitis in a patient with incontinentia pigmenti.

A large number of diseases can mimic a vasculitis. The diagnosis can be challenging due to the similarity with several diseases that have a different pathogenesis. As reported in the literature, incontinentia pigmenti (IP), a rare genetic disorder, can present vascular alterations on eye, brain and lung. We report a case of peripheral arterial disease in a patient with IP, suggesting further vascular localizations of the disease.

Alopecia areata universalis during off-label treatment with Infliximab in a patient with Behçet disease.

Infliximab, a chimeric monoclonal anti-TNF-alfa agent used to treat autoimmune diseases, has shown a paradoxical side effect in the development of autoimmunity. We describe a case of alopecia areata universalis associated with infliximab treatment in a patient with Behçet disease. This case suggests a complex and contradictory role of TNF-α in the pathogenesis of alopecia areata.

Devic's syndrome and primary APS: a new immunological overlap.

Neuromyelitis optica (NMO or Devic's syndrome) is a rare autoimmune disease, previously considered a multiple sclerosis variant. The most important laboratory and clinical features are optic myelitis and transverse myelitis, associated with neuromyelitis optica-IgG antibody (NMO-IgG) positivity. Subsequent to this immunological test being available, different groups have described the not-so-rare comorbidity of neuromyelitis optica with other systemic autoimmune diseases, systemic lupus erythematosus with secondary anti-phospholipid syndrome (APS) in particular. We describe a patient meeting both the classification criteria for primary APS and the new diagnostic criteria for neuromyelitis optica. It's important to diagnose NMO syndrome as both optic neuritis and transverse myelitis were also considered neurological complications of antiphospholipid syndrome. NMO-IgG is a new and fundamental test to decide if immunosuppressant therapy is warranted for such patients.

Infliximab for the treatment of posterior uveitis with retinal neovascularization in Behçet disease.

PURPOSE: To report a case of posterior uveitis with retinal neovascularization in a patient with Behçet disease treated with infliximab. METHODS: A 50-year-old man with a history of recurrent relapses of ocular inflammation despite immunosuppressive therapy developed retinal neovascularization near the optic disk. The patient was treated with infliximab and followed up for 12 months. RESULTS: Retinal neovascularization regressed 8 months after the first anti-tumor necrosis factor (TNF) treatment and with six infusions of infliximab. The ocular inflammation resolved almost completely. CONCLUSIONS: The result suggests that anti-TNF therapy may be effective in the treatment of retinal neovascularization caused by panuveitis in Behçet disease.

Infliximab for the treatment of posterior uveitis with retinal neovascularization in Behet disease.

PURPOSE: To report a case of posterior uveitis with retinal neovascularization in a patient with Behet disease treated with infliximab. METHODS: A 50-year-old man with a history of recurrent relapses of ocular inflammation despite immunosuppressive therapy developed retinal neovascularization near the optic disk. The patient was treated with infliximab and followed up for 12 months. RESULTS: Retinal neovascularization regressed 8 months after the first antitumor necrosis factor (TNF) treatment and with six infusions of infliximab. The ocular inflammation resolved almost completely. CONCLUSIONS: The result suggests that anti-TNF therapy may be effective in the treatment of retinal neovascularization caused by panuveitis in Behet disease. (Eur J Ophthalmol 2004; 14: #-8).

The role of intravenous immunoglobulin therapy in autoimmune and inflammatory disorders.

The first use of immunoglobulin therapy, historically, was in 1890 when Emil von Behring developed effective antiserum against diphtheria toxin, but only in the early 1970s technological advancements in the fractionation of plasma lead to the production of Ig preparations which could be administered intravenously. Intravenous Ig products are a mainstay for disorders such as: primary immunodeficiency, serious infections, autoimmune and inflammatory disorders. During autoimmune and systemic inflammatory disease IVIg exhibits a number of immune modulatory activities such as: Fc Receptor-mediated effects, modulation of complement, modulation of cytokine production, superantigens neutralization, antibodies neutralization by idiotype network, increased catabolism of IgG, but also biologic effects of other molecules present in IVIg preparations. Recent understanding about IVIg composition and mechanism of action can explain its therapeutic effect in autoimmune and inflammatory disorders. Nevertheless it is important to underline that IVIg is a heterogeneous product and it is difficult to determine the exact mechanism of its activities in every disease. The increased use of IVIg in the treatment of autoimmune disorders outlined the issue of tolerability. Undesiderable effects to IVIg occurs in less than 5% of patients.

Use of technetium-99m hexamethylpropylene amine oxime SPET for the study of cerebral blood flow reactivity after acetazolamide infusion in patients with Behçet's disease.

The purpose of this study was to characterise the nature of the baseline perfusion defects found in patients with Behçet's disease using hexamethylpropylene amine oxime single-photon emission tomography in conjunction with acetazolamide test (Acz SPET). Eleven patients underwent both baseline and Acz SPET. Regions of interest (ROIs) were drawn on the areas with decreased perfusion (D-ROI) and, in the same section, on areas with normal perfusion (N-ROI). The ROIs were then repositioned on the corresponding section on Acz SPET. The mean ROI counts were then transformed into a perfusion index value (PIV) with reference to the global brain counts. In total we found 24 D-ROIs (17 in the cortical and 7 in subcortical grey matter). The influence of Acz infusion was selectively registered in the D-ROIs, where PIVs changed from 1.23+/-0.17 (baseline SPET) to 1.63+/-0.23 (Acz SPET) (P<0.001). No significant difference was seen in the N-ROIs (1.46+/-0.21 and 1.40+/-0.17, respectively, on baseline SPET and Acz SPET). Our results demonstrate that Acz infusion increases the regional cerebral blood flow within baseline grey matter perfusion defects. This finding suggests that baseline perfusion abnormalities could reflect a disconnection rather than local vasculitic involvement.

A double-blind, placebo-controlled comparison of treatment with fluticasone propionate and levocabastine in patients with seasonal allergic rhinitis. FLNCO2 Italian Study Group.

Fluticasone propionate aqueous nasal spray (FPANS) is a topically active glucocorticoid which has been successfully used for the treatment of seasonal allergic rhinitis (SAR). Topical levocabastine is a highly selective H1 antagonist which has been proposed as an alternative treatment of SAR. The purpose of this study was to compare the clinical efficacy of two topical nasal treatments, FPANS and levocabastine, in the treatment of SAR. Additionally, the effect of treatments on nasal inflammation was examined during natural pollen exposure. A group of 288 adolescent and adult patients with at least a 2-year history of SAR to seasonal pollens participated in a multicenter, doubleblind, double-dummy, and placebo-controlled study. Patients were treated with either FPANS 200 microg, once daily (n = 97), or topical levocabastine, 200 microg, given twice daily (n = 96), or matched placebo (n = 95) for a period of 6 weeks, starting from the expected beginning of the pollen season. Clinically relevant pollens included Parietaria, olive, and grass. Assessment of efficacy was based on scores of daily nasal symptoms and on nasal cytology of nasal lavage. Nasal lavage was performed immediately before, during, and at the end of treatment in 39 patients. FPANS significantly increased the percentage of symptom-free days for nasal obstruction on waking and during the day, rhinorrhea, sneezing, and itching. FPANS provided a better control for night and day nasal obstruction (P<0.02 and P<0.01) and rhinorrhea (P<0.01) than levocabas tine. In addition, fewer patients treated with FPANS used rescue medication (P<0.025). The percentage of eosinophils in nasal lavage was reduced only during treatment with FPANS. The results of this study indicate that FPANS 200 microg, once daily, provides a better clinical effect than levocabastine 200 microg, twice daily, in patients with SAR. Unlike levocabastine, FPANS significantly attenuates nasal eosinophilia during pollen exposure, a feature which may explain its therapeutic efficacy.

Type 2 helper T-cell predominance and high CD30 expression in systemic sclerosis.

The pattern of cytokine production of skin-infiltrating T cells from patients with progressive systemic sclerosis was investigated. Most CD4+ T-cell clones generated from skin biopsy specimens showed a type 2 helper (Th2) cytokine profile (production of interleukin-4, but no interferon (IFN)-gamma). High interleukin-4 but little or no IFN-gamma mRNA expression was found by in situ hybridization in skin perivascular mononuclear cell infiltrates. The immunohistochemical analysis revealed CD30 expression by high numbers of CD4+ T cells in the same specimens. Finally, the great majority of patients with diffuse disease had elevated levels of soluble CD30 in their sera. These data suggest the existence in patients with progressive systemic sclerosis of a predominant activation of Th2-like T cells, which may account for the major alterations (endothelial cell injury, fibrosis, and autoantibody production) occurring in this disease.

Possible pathogenetic role of activated platelets in the primary antiphospholipid syndrome involving the central nervous system.

Neurological disorders occurring in the primary antiphospholipid syndrome (neuro-PAPS) have not yet been completely understood. Platelet activation has been suggested to play a crucial role in the pathogenesis of hemostatic disorders in the antiphospholipid syndrome, but no association with neuro-PAPS has been investigated so far. Therefore, we investigated 16 patients with PAPS by flow cytometry in the presence of circulating activated platelets as defined by the surface expression of activation-dependent glycoprotein CD62. In addition, the relationship among activated platelets and anticardiolipin antibodies (aCL) was evaluated. Compared to normal subjects CD62 was found significantly increased in these patients. Furthermore, a significantly increased percentage of CD62-positive platelets was found in the neuro-PAPS group (nine patients) compared to the non-neuro-PAPS patients (seven subjects). On the contrary, no significant difference was found between the two groups with regard to aCL IgG and platelet number. Furthermore, within the neuro-PAPS group, no difference was evidenced, in the CD62-positive platelet percentage, between the four subjects with thrombocytopenia and the five with the normal blood platelet count. Similarly, neuro-PAPS subjects with previous peripheral arterial and/or venous thrombosis did not show a significantly more elevated level of CD62-positive platelets. Finally, a linear correlation was found between the aCL IgG level and the CD62-positive platelet percentage in all the patients and, more significantly, in the neuro-PAPS group, but not within the non-neuro-PAPS patients. Our data demonstrate that circulating activated platelets are detectable by flow cytometry in the majority of PAPS patients and suggest the existence of a relationship among activated platelets, aCL, and neurological disease that patients affected by PAPS might undergo.

Flow cytometric detection of circulating activated platelets in primary antiphospholipid syndrome. Correlation with thrombocytopenia and anticardiolipin antibodies.

Platelet activation has been suggested to play a crucial role in the pathogenesis of haemostatic disorders in antiphospholipid syndrome (APS). In 16 patients with primary APS (PAPS) we investigated by flow cytometry the presence of circulating activated platelets as defined by the surface expression of activation-dependent glycoproteins CD62 and CD63. In addition, the relationships among activated platelets, thrombocytopenia, antiphospholipid antibodies (aPL) and platelet associated IgG (PalgG) were evaluated. Compared to normal subjects CD62, but not CD63 expression, was found significantly increased in patients. All thrombocytopenic subjects showed a percentage of CD62 expressing platelets above the cut off. In thrombocytopenics a significantly increased percentage of CD62 and higher levels of aCL IgG were found compared to PAPS patients with normal platelet count. No correlation was found between activated platelets and both lupus anticoagulant antibodies and PalgG. Our data demonstrate that circulating activated platelets are detectable by flow cytometry in the majority of PAPS patients and suggest the existence of a relationship among activated platelets, thrombocytopenia and aPL levels.

Pathogenesis and therapy of Behçet's disease.

Behçet's disease is a relapsing-remitting systemic vasculitis characterized by oral and genital ulcers, uveitis and thrombophlebitis which can involve many organs. Although its pathogenesis is not fully understood, a possible pathogenetic model can be proposed on the basis of recent studies. Genetic factors, in particular, have been investigated and the role of the genes encoding tumor necrosis factor, transporter in antigen processing proteins and MIC (MHC class I chain related) has been emphasized. In addition, a possible polarization of T lymphocytes towards the Th1 phenotype in Behçet's disease has been suggested by recent observations in experimental uveoretinitis and by preliminary data in humans. Neutrophils may also play a role in the pathogenesis of this disease, as they are attracted by macrophage-released cytokines at the site of the lesions, and thus contribute to tissue damage and self-maintenance of inflammation. New strategies for the treatment of Behçet's disease are being devised. In particular, immunosuppressive drugs used in association or in sequence may be administered to patients with particular clinical features or very severe disease.