1,720,969 research outputs found
Does polymorphysm of genes coding for pro-inflammatory mediators predict the clinical response to tnf alpha blocking agents? A review analysis of the literature
No full textTumor necrosis factor-α (TNF-α) has a key role in the pathogenesis of rheumatoid arthritis (RA) and the introduction of anti-TNFα biological therapies has dramatically altered the treatment of RA. Anti-TNFα agents display good clinical efficacy in patients resistant to traditional disease-modifying antirheumatic drugs and superior efficacy in the suppression of erosive joint damage, even if a significant non-response rate has been reported (30-40%). Because anti-TNFα therapy is associated with expensive treatment costs, leading to restrictions in the numbers of patients who may be treated, the identification of predictors of treatment outcome may improve the cost-effectiveness of anti-TNFα therapies. Several candidate gene studies have addressed this topic, but they have had limited success in identifying predictors. It is not clear whether the response to anti-TNFα treatment will be conferred through a number of genes, each with a small effect size, or whether genes may predict the outcome of the treatmen
Choroidal impairment and macular thinning in patients with systemic sclerosis : the acute study
No full textRaynaud's phenomenon (RP) is a reversible vasospastic response of the extremities to cold or emotion, and can be the first manifestation or may be present before the development of an overt systemic sclerosis (SSc). The disturbance of the balance between vasodilation and vasoconstriction is not limited to the peripheral microcirculation of the skin, but it is also observed in other organs, such as the choroidal plexus of the eye. We aimed to examine the choroidal thickness (CT), the macular thickness and ganglion cell complex (GCC) average in thirty consecutive patients, without visual symptoms, classified as primary RP (pRP), RP secondary to suspected SSc, and overt SSc. All the patients underwent rheumatologic and ophthalmologic examination, capillaroscopy, test for anti-nuclear antibodies, anti-dsDNA, and anti-extractable nuclear antigens. Ophthalmologic examination included: best corrected visual acuity; slit lamp biomicroscopy; intraocular pressure measurements, fundus examination, and Spectral Domain-Optical Coherence Tomography (SD-OCT) with enhanced depth imaging scan system. Twenty-seven healthy subjects similar for gender and age were analyzed. In pRP, CT was significantly thinner than controls in the outer nasal and temporal regions. In secondary RP, the inner and outer nasal areas were significantly thinner than controls. In SSc, the central, inner inferior, inner nasal, inner superior, outer temporal, outer inferior, and outer nasal regions were significantly thinner than controls. A decreasing trend of central foveal thickness was noted. All the patients had GCC average significantly lower than controls. A thinning of choroidal and macular thickness, as well as of GCC was observed in patients with pRP and becomes more severe and extensive in RP secondary to suspected SSc and overt SSc. To our knowledge, this is the first study to analyze the choroidal features using SD-OCT in RP. These data may be clinically useful in suggesting an early involvement of ocular microcirculation with significant reduction of choroidal perfusion
Hand impairment in systemic sclerosis : association of different hand indices with organ involvement
No full textOBJECTIVE: To evaluate the association between the assessment tools used to quantify hand impairment and organ involvement in patients with systemic sclerosis (SSc).
METHODS: Eighty consecutive SSc patients were assessed for hand impairment using the Hand Anatomic Index (HAI), finger-to-palm distance in flexion (FTP), and the Hand Mobility in Scleroderma (HAMIS) test. Cluster analysis was used to identify patients having similar characteristics on the basis of the pattern of organ involvement in order to create clinically homogeneous groups, and to correlate these clusters with the measures of hand involvement. Finally, we evaluated the discriminating ability of the indices to identify the patients whose clinical condition was more severe.
RESULTS: Two major clusters were identified by cluster analysis on the basis of organ involvement. The first (cluster A) included 61 patients and the second (cluster B) 19 patients characterized by minor and major extent of organ involvement, respectively. The extent of organ involvement and the hand impairment were related. The scores of hand indices were lower in cluster B. The area under the receiver operating characteristic (ROC) curve (C-index) for the logistic model including all three indices was 0.85 (95% confidence interval 0.74–0.95).
CONCLUSION: The seriousness of hand involvement as measured by the three indices was associated with the extent of organ involvement. Further studies of hand impairment scales are needed to provide validated guidance as meaningful clinical measures
Reduction of haemostatic and inflammatory biomarkers by tumor necrosis factor-alpha bockade in patients with rheumatoid arthritis
No full textChoroidal Changes in Patients with Raynaud’s Phenomenon Secondary to a Connective Tissue Disease : Study of Vascular Eye Involvement in Patients Affected by Raynaud’s Phenomenon with in vivo Noninvasive EDI-OCT
No full textActivation of inflammation, coagulation and fibrinolysis in patients with Rheumatoid Arthritis : inhibition by Tumor Necrosis Factor alpha blockade
No full textObjective: Rheumatoid arthritis (RA) is associated with increased
cardiovascular risk and activation of inflammation and coagulation
pathways. Its treatment with infliximab, a chimeric monoclonal
antibody to tumour necrosis factor-a (TNF-a), reduces inflammation,
but its effects on coagulation and fibrinolysis are unknown.
We therefore investigated plasma biomarkers of inflammation,
coagulation and fibrinolysis before and after infliximab treatment in
RA patients.
Methods: We studied 18 patients with active RA and 36 healthy
controls. RA patients, receiving a stable dose of methotrexate
(10 mg/week), were treated with infliximab (3 mg/kg) at week 0, 2,
6 and 14. At baseline and at week 14, we determined: disease
activity score (DAS28), visual analogue scale (VAS) pain, erythrocyte
sedimentation rate (ESR), and plasma levels of C-reactive
protein (CRP), TNF-a, IL-6, prothrombin fragment 1+2 (F1+2) and
D-dimer. In six patients, we also evaluated inflammation and
coagulation parameters one hour after infliximab infusion.
Results: At baseline, ESR, CRP, TNF-a and IL-6 levels were
significantly higher in the RA patients (p=0.001–p=0.0001), as
were F1+2 and D-dimer levels (p=0.0001). After 14 weeks of
infliximab treatment, there was a significant clinical improvement
(decrease in DAS28, VAS pain, number of swollen and tender
joints) and a significant decrease in ESR and CRP, IL-6, F1+2 and Ddimer
levels (p=0.03–p=0.003). The levels of TNF-a, IL-6, F1+2
and D-dimer significantly decreased one hour after infliximab
infusion (p=0.05–p=0.008).
Conclusions: In RA patients, infliximab leads to a rapid clinical
improvement and a decrease in inflammation and coagulation
biomarkers. The reduction in the latter suggests that it may reduce
thrombotic risk
Cutaneous Manifestations of ANCA-Associated Small Vessels Vasculitis
No full textSkin lesions are frequent manifestations of underlying systemic conditions, including systemic autoimmune vasculitis. In particular, anti-neutrophil cytoplasmic antibodies (ANCA) are associated with distinct forms of vasculitis characterized by inflammatory cell infiltration of the walls of small and medium-sized vessels leading to vascular destruction and tissue necrosis. ANCA-associated vasculitis is rare and systemic diseases, which can be classified based on different distribution of vascular inflammation and presence or absence of granulomatosis and asthma. Despite their diversities, ANCA-associated vasculitis, namely microscopic polyangiitis, granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis, can all display a broad variety of cutaneous manifestations, which can appear during the course of the disease or even as first sign at the time of onset. Different skin manifestations might coexist in the same patient and occur in different occasions during the course of the vasculitis. Thus, a deep knowledge of the spectrum of skin lesions as part of ANCA-associated vasculitis is mandatory for a correct diagnostic process, whenever cutaneous vasculitis is suspected. Due to this broad variety of manifestations, the diagnosis of skin involvement in ANCA-associated vasculitis is very challenging and it must be supported by a detailed medical history, accurate physical examination, specific histopathological analysis of skin biopsy and the presence of ANCA serology. In this review, we focus on the cutaneous manifestations that can develop in the context of ANCA-associated vasculitis, detailing the clinical features, the histopathological aspects as well as the direct immunofluorescence studies for each of the three conditions. Moreover, we acknowledged the differential diagnoses that must be ruled out in the diagnostic process and the main therapeutic approaches available for treatment of ANCA-associated vasculitis
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