BackgroundThe aim was to study changes in immunohistochemical expression markers of synovial and skin inflammation, clinical outcomes and magnetic resonance imaging (MRI) scores with abatacept treatment in patients with psoriatic arthritis (PsA).MethodsBiological-treatment-naïve PsA patients with active disease including synovitis of a knee were enrolled in this single-centre, crossover study. Patients were randomised to receive intravenous abatacept 3 mg/kg of body weight or placebo infusion on day 1, 15 and 29; thereafter abatacept 10 mg/kg of body weight was administered every 28 days for 5 months. Clinical data were collected at each visit. Synovial biopsy of the involved knee was obtained at baseline and 2 and 6 months. MRI of the same knee and skin biopsy was performed prior to arthroscopy.ResultsFifteen patients were recruited. Significant improvements in the joint-related measures were observed; 90% were European League Against Rheumatism criteria responders and 30% achieved psoriasis area severity index (PASI)50 at 6 months. Reduction in synovitis (P = 0.016) and vascularity (P = 0.039) macroscopic scores consistent with decrease in total MRI score (P = 0.016) were noticed. Abatacept decreased the immunohistological expression of FOXP3+ cells (P = 0.027), specifically the expression of CD4+FOXP3+ regulatory T cells (Tregs) (P = 0.008) in the synovium over 6 months. There was no significant clinical or immunohistological change in any of the skin measures.ConclusionThis is the first study assessing synovial and psoriatic skin immunpathological changes following abatacept treatment in PsA. Reduction in Treg expression in the synovium but not in the psoriatic lesion suggests abnormal Treg function in PsA with differential suppressive capacity in the synovium compared to the lesional skin. The results of this study demonstrate that abatacept 10 mg/kg of body weight might be an effective treatment option for joint disease in patients with PsA.Trial registrationIrish Health Products Regulatory Authority. Trial registration number: CT 900/489/1 – Abatacept (case number: 2077284, EudraCT Number: 2009-017525-19, Protocol number: 77777). Registered on 12 March 2010.
Case: A 67-year-old female presented with an exceedingly rare cardiac neoplasmpapillary fibroelastoma. This is made rarer still as it occurred on the pulmonary valve. The patient complained of a prolonged history of chest discomfort. Magnetic resonance imaging and echocardiography revealed a pulmonary valve papillary fibroelastoma. Surgical excision proved curative and the patient remains asymptomatic to date. Discussion: The literature surrounding papillary fibroelastomas is discussed. Primary cardiac tumours are uncommon. Papillary fibroelastomas occurring the right side of the heart comprise less than 0.05% of these. They have a characteristic macroscopic appearance which allow them to be easily identified with echocardiography and at surgical excision. They can present in a variety of ways including classical cardiac symptoms, embolic complications or as an incidental finding. Surgical excision is the definitive treatment.
BackgroundAbatacept is a fully human fusion protein which selectively inhibits T-cell activation via the CD80/CD86:CD28 co-stimulation pathway and decreases serum levels of inflammatory cytokines and proteins implicated in the pathogenesis of psoriatic arthritis (PsA). Improvement in skin psoriasis with greatest reduction in PASI using 3 mg/kg dose of abatacept and reduction of clinical symptoms of PsA on 10 mg/kg dose has been previously shown. Data is limited on the immunopathological effect of abatacept in PsA synovial tissue.Objectives(1) to study the change in immunohistochemical markers of synovial inflammation from baseline to 6 months after introducing abatacept treatment in patients with active PsA; (2) to evaluate the impact of a short period of abatacept 3 mg/kg treatment on both skin and joint-related clinical outcomes compared to placebo (PBO); (3) to investigate if cell markers of synovial inflammation correlate to disease activity measures and MRI synovitis scores.MethodsBiological treatment-naïve PsA patients with active disease for ≥3 months with clinical synovitis of a knee and the presence of a psoriatic skin lesion were enrolled. Patients were randomised to receive abatacept 3mg/kg or PBO infusion on day 1, 15 and 29; thereafter abatacept 10mg/kg was administered every 28 days for 5 months. Clinical data were collected at each visit.Ga-enhanced MRI and arthroscopic synovial biopsy of the involved knee were obtained at 0, 2 and 6 months. Immunohistological staining for CD3, CD4, CD8, FoxP3 and CD31 was performed and expression was scored on a 5 point scale using a semi-quantitative method [1]. FoxP3 (%/300 cells) and CD31 expression (number of positive vessels/10 HPF) was evaluated. The PsAMRIS semi-quantitative method was used to score MRI scans by one consultant radiologist. A total synovitis score (MRS (0-12)) per knee was calculated [2].Results15 patients (8 female/7 male) with mean age of 45 (±14.6) years were recruited. 4 were on methotrexate, the remainder had not received any prior DMARDs. 73% and 80% of patients were EULAR responders at 2 and 6 months. Non responders had significantly higher CRP at basleline; ESR, CRP, DAS28 ESR and DAS28 CRP at 2 months and higher enthesitis scores at 6 months compared to responders.Preliminary synovial tissue analysis of the first 10 patients who completed the study revealed a reduction in expression for all cell markers as early as 2 months following treatment. There was a significant reduction in synovial CD4 expression at 6 months (p=0.038). Disease activity measures and cell markers did not show a significant difference between the treatment and PBO groups. MRS at baseline was lower (p=0.02) and change in DAS28 ESR 0 to 6 months was greater in the PBO group (p=0.08). Baseline DAS28 ESR significantly correlated with CD3, CD4 and FoxP3 expression at 6 months (rho=0.89 p=0.04).ConclusionsAbatacept reduced synovial CD4 positive T-cell expression in psoriatic arthritis over 6 months. DAS28 ESR at baseline correlated with all observed T-cell markers in ...
A man in his 80s had a 4-week history of progressive weakness and fatigue, with associated development of purple bruiselike lesions on his head. What is your diagnosis?
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