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1.
J Eur Acad Dermatol Venereol ; 30(9): 1531-6, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27393182

ABSTRACT

BACKGROUND: There are conflicting data on the occurrence of subclinical myocardial dysfunction in psoriatic patients and on the impact of long-term tumour necrosis factor-alpha (TNF-α) inhibitor therapy on cardiac function. OBJECTIVE: In this study, we explored whether there are any signs of subclinical cardiovascular disease (echocardiographic abnormalities) in severe psoriatic patients without clinically overt heart disease. As a second objective, the influence of long-term treatment with TNF-α inhibitors on the ventricular functions of psoriatic patients was also investigated. METHODS: Clinical and echocardiographic data from 44 psoriatic patients and 45 age- and sex-matched controls were processed. As a first step, the echocardiographic parameters of psoriatic patients obtained before anti-TNF-α treatment were compared with controls. As a second step, to detect the effect of long-term anti-TNF-α treatment on echocardiographic parameters, data of patients before and after therapy were analysed. RESULTS: The right ventricular Tei index was higher (P < 0.001), whereas the tricuspid annular plane systolic excursion (TAPSE) and right ventricular free wall peak systolic velocity were lower (P < 0.001 and P < 0.0001, respectively) in the psoriatic patients than in the controls. Following treatment with TNF-α inhibitors, TAPSE and right ventricular free wall peak systolic velocity significantly improved (P < 0.0001 for both parameters). The Tei index of both ventricles improved during biological therapy; however, this change did not reach statistical significance. CONCLUSION: Patients with severe psoriasis exhibit signs of subclinical cardiovascular disease compared to control, and prolonged anti-TNF-α therapy has a potentially beneficial effect on these signs.


Subject(s)
Cardiovascular Diseases/complications , Dermatologic Agents/therapeutic use , Psoriasis/drug therapy , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adult , Cardiovascular Diseases/diagnostic imaging , Echocardiography , Female , Humans , Male , Middle Aged , Psoriasis/complications
2.
Lupus ; 21(13): 1412-22, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22864236

ABSTRACT

The aim of the present study was to assess the autoantibody profile, dominant clinical symptoms and cluster characteristics of different mixed connective tissue disease (MCTD phenotypes. Two-hundred-and-one patients with MCTD were followed-up longitudinally. Five clinical parameters, Raynaud's phenomenon, pulmonary artery hypertension (PAH), myositis, interstitial lung disease (ILD), erosive arthritis and five auto-antibodies besides anti-U1RNP, antiendothelial cell antibodies (AECA), anti-CCP, anti-cardiolipin (anti-CL), anti-SSA/SSB and IgM rheumatoid factor (RF) were selected for cluster analysis. The mean age of patients was 52.9 ± 12.4 years and the mean follow-up of the disease was 12.5 ± 7.2 years. Patients were classified into three cluster groups. Cluster 1 with 77 patients, cluster 2 with 79 patients and cluster 3 with 45 patients. In cluster 1 the prevalence of PAH (55.8%; p < 0.001), Raynaud's phenomenon (92.2%; p < 0.001) and livedo reticularis (24.6%, p < 0.001) was significantly greater than in cluster 2 and 3. In cluster 2, the incidence of ILD (98.7%; p < 0.001), myositis (77.2%; p < 0.001), and esophageal dysmotility (89.8%; p < 0.001) was significantly greater than that in cluster 1 and 3. In cluster 3, anti-CCP antibodies were present in 31 of 45 patients (68.8%) with erosions. Anti-CCP antibodies were present in 37 of 42 patients (88.0%) with erosions. PAH, angina, venous thrombosis was observed in cluster 1 and pulmonary fibrosis in cluster 2, musculosceletal damage, gastrointestinal symptoms and osteoporotic fractures were most frequent in cluster 3. Cumulative survival assessment indicated cluster 1 patients having the worst prognosis. Cluster analysis is valuable to differentiate among various subsets of MCTD and useful prognostic factor regarding the disease course.


Subject(s)
Mixed Connective Tissue Disease/epidemiology , Adult , Aged , Analysis of Variance , Arthritis/epidemiology , Autoantibodies/blood , Biomarkers/blood , Chi-Square Distribution , Cluster Analysis , Disease Progression , Familial Primary Pulmonary Hypertension , Female , Humans , Hungary/epidemiology , Hypertension, Pulmonary/epidemiology , Incidence , Longitudinal Studies , Lung Diseases, Interstitial/epidemiology , Male , Middle Aged , Mixed Connective Tissue Disease/classification , Mixed Connective Tissue Disease/diagnosis , Mixed Connective Tissue Disease/immunology , Mixed Connective Tissue Disease/mortality , Myositis/epidemiology , Phenotype , Prevalence , Prognosis , Raynaud Disease/epidemiology , Survival Analysis , Time Factors
3.
Scand J Rheumatol ; 35(4): 300-4, 2006.
Article in English | MEDLINE | ID: mdl-16882595

ABSTRACT

OBJECTIVE: To determine the percentage and absolute number of CD4+ regulatory T-cells (Treg) in 48 patients with mixed connective tissue disease (MCTD). METHODS: Data were classified on the basis of the stage of the disease: 17 patients were in the active stage and 31 in the inactive stage. The absolute number of CD4+/intracellular interleukin-10+ (IL-10+) and CD4+CD25+high Treg cells was determined by flow cytometry. The percentage of CD4+CD25+high suppressor T-cells was determined on the basis of Foxp3 expression. RESULTS: The percentage and the absolute number of CD4+CD25+high Treg cells were lower in patients than in healthy controls (p<0.04), and were further decreased in patients with active MCTD and were lower than in the inactive stage (p<0.01). There was an increase in the percentage and absolute number of CD4+IL-10+ Treg cells in patients with MCTD compared to the healthy controls (p<0.02). The percentage of CD4+IL-10+ Treg cells was higher in the active stage of MCTD than in the inactive stage of the disease (p<0.005). However, we did not find any significant difference in the absolute number of CD4+IL-10+ Treg cells between the patients in the active and inactive stages of MCTD. CONCLUSION: Our results suggest that the decrease in the number of CD4+CD25+high Treg cells in an important factor in the immunoregulatory disturbance in patients with MCTD. We suggest that the increase in the number of CD4+IL-10+ Treg cells is a compensatory mechanism aiming to restore the balance between type 1 and type 2 cytokines in MCTD.


Subject(s)
Mixed Connective Tissue Disease/blood , T-Lymphocytes, Regulatory/metabolism , Adult , Female , Humans , Interleukin-10/metabolism , Male , Middle Aged , Receptors, Interleukin-2/metabolism
4.
Scand J Immunol ; 64(1): 69-76, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16784493

ABSTRACT

We investigated the clinical characteristics and immunoserological alterations in patients with mixed connective tissue disease (MCTD) associated with pulmonary arterial hypertension (PAH). Anti-U1RNP autoantibodies, anti-endothelial cell antibodies (AECA) and serum thrombomodulin (TM) as well as von Willebrand factor antigen (vWFAg) concentrations were measured in 25 patients with MCTD associated with PAH and in 154 MCTD patients without PAH. The results showed that the probability of survival was lower in MCTD patients with PAH than in the 154 MCTD-non-PAH patients (5-year survival rate in MCTD with PAH: 73%, versus 96% in MCTD-non-PAH; P < 0.01). AECA were more frequently present in the sera of MCTD patients with PAH than in MCTD-non-PAH (P < 0.001). Serum TM and vWFAg levels were higher in MCTD-PAH patients than in MCTD-non-PAH patients (TM: P < 0.001; vWFAg: P < 0.001). Significant correlation was noticed between the quantity of AECA and TM level (r = 0.466) as well as the quantity of AECA and vWFAg level (r = 0.550). In conclusion, our results suggest that in MCTD the presence of AECA and endothelial cell activation may play a role in the development of PAH and in the maintenance of obliterative vascular processes.


Subject(s)
Hypertension, Pulmonary/etiology , Mixed Connective Tissue Disease/complications , Pulmonary Artery/physiopathology , Adult , Antibodies, Anticardiolipin/blood , Antibodies, Anticardiolipin/immunology , Antibodies, Antinuclear/blood , Antibodies, Antinuclear/immunology , Autoantibodies/blood , Autoantibodies/immunology , Echocardiography, Doppler , Female , Humans , Hypertension, Pulmonary/immunology , Hypertension, Pulmonary/physiopathology , Male , Middle Aged , Mixed Connective Tissue Disease/immunology , Mixed Connective Tissue Disease/physiopathology , Ribonucleoprotein, U1 Small Nuclear/immunology , Survival Analysis
5.
Rheumatology (Oxford) ; 44(5): 656-61, 2005 May.
Article in English | MEDLINE | ID: mdl-15716315

ABSTRACT

OBJECTIVE: Interstitial lung disease (ILD) may be a characteristic, often serious, manifestation of mixed connective tissue disease (MCTD). In this retrospective study, the frequency and clinical picture of ILD were determined in patients with MCTD using two diagnostic tests: high-resolution computed tomography (HRCT) and inhaled aerosol clearance times of (99m)Tc-labelled diethylene-triamine pentaacetate ((99m)Tc-DTPA). In addition, pulmonary function, effects of therapy and a variety of immunoserological markers were also assessed. METHODS: One hundred and forty-four consecutive patients with MCTD were selected from the clinic, irrespective of the presence or absence of ILD. All patients underwent a detailed clinical assessment, chest HRCT scanning, chest radiography, inhaled aerosol of (99m)Tc-DTPA clearance times, and all pulmonary function tests. Patients who had active ILD received corticosteroid (CS) or CS in combination with cyclophosphamide (CPH). All investigations were repeated after 6 months of immunosuppressive therapy. RESULTS: Ninety-six out of 144 MCTD patients (66.6%) had active ILD, 75 of this group (78.1%) showed ground glass opacity, 21 patients (21.8%) ground glass opacity with mild fibrosis with HRCT. Forty-five patients with active ILD received 2 mg/kg/day CS for 6-8 weeks alone and 51 patients CS in combination with CPH (2 mg/kg/day). Six months later, after therapy, 67 out of 96 MCTD patients with ILD (69.8%) showed a negative HRCT pattern, ground glass opacity with mild fibrosis developed in 15 patients (15.6%), and fibrosis was detected in 13 patients (13.5%). Only one patient showed subpleural honeycombing. (99m)Tc-DTPA was rapid in all 96 MCTD patients with active ILD (28.7 +/- 8.2 min, normal value >40 min). After therapy the (99m)Tc-DTPA was normalized, 79 out of 96 patients (82.3%). Carbon monoxide diffusion capacity (DLCO) was reduced in 33 out of 96 MCTD patients with active ILD (34.3%), while there were no significant differences in the pulmonary function tests between the active versus inactive stage of ILD or versus patients without ILD. The sera of 96 MCTD patients with active ILD contained a high level of immune complexes (ICs), and the total haemolytic complement levels (CH50/ml U) decreased. After 6 months of therapy, the IC levels decreased and CH50/ml levels normalized (MCTD patients before and after active ILD: IC optical density = 355 +/- 227 vs 206 +/- 92, P<0.001; CH50/ml, 38.0 +/- 12.6 U vs 64.3 +/- 13.0 U, P<0.001). CONCLUSIONS: HRCT is the gold standard for diagnosis of ILD. However, we used another method, (99m)Tc-DTPA, in order to compare this technique with HRCT. This latter technique has not been studied previously in MCTD. The elevated levels of IC and increased complement consumption indicated that IC-mediated alveolocapillary membrane damage and tissue injury might play a role in the pathogenesis of ILD in MCTD.


Subject(s)
Lung Diseases, Interstitial/etiology , Mixed Connective Tissue Disease/complications , Adult , Aged , Cyclophosphamide/therapeutic use , Drug Therapy, Combination , Female , Glucocorticoids/therapeutic use , Humans , Lung Diseases, Interstitial/diagnosis , Lung Diseases, Interstitial/diagnostic imaging , Lung Diseases, Interstitial/drug therapy , Male , Methylprednisolone/therapeutic use , Middle Aged , Radionuclide Imaging , Radiopharmaceuticals , Respiratory Function Tests , Retrospective Studies , Technetium Tc 99m Pentetate , Tomography, X-Ray Computed
6.
Haematologia (Budap) ; 30(4): 303-11, 2000.
Article in English | MEDLINE | ID: mdl-11204029

ABSTRACT

Antiphospholipid syndrome is characterized by the presence of antiphospholipid antibodies resulting in arterial and venous thromboembolism. Apart from primary cases, this syndrome is often associated with autoimmune diseases. Around 50 cases of catastrophic antiphospholipid antibody syndrome have been reported as yet. Authors describe the first case of catastrophic antiphospholipid syndrome associated with gastric cancer. Apart from presenting the clinical case, authors also discuss the possible pathomechanism of this associated disorder including the role of immunological factors, as well as antiphospholipid antibodies.


Subject(s)
Antiphospholipid Syndrome , Stomach Neoplasms , Fatal Outcome , Female , Humans , Middle Aged
7.
Orv Hetil ; 140(52): 2917-20, 1999 Dec 26.
Article in Hungarian | MEDLINE | ID: mdl-10659644

ABSTRACT

Antiphospholipid syndrome is characterized by the presence of antiphospholipid antibodies resulting in arterial and venous thromboembolism. Apart from primary cases, this syndrome is often associated with autoimmune diseases. Around 50 cases of catastrophic antiphospholipid antibody syndrome have been reported as yet. Authors describe a case of a female patients with catastrophic antiphospholipid syndrome associated with gastric cancer. This may be the first case of such association in the literature. Authors also discuss the possible pathomechanism of this disorder, as well as the available therapeutic approaches.


Subject(s)
Adenocarcinoma/pathology , Antibodies, Antiphospholipid/immunology , Stomach Neoplasms/pathology , Adenocarcinoma/immunology , Fatal Outcome , Female , Humans , Middle Aged , Stomach Neoplasms/immunology , Syndrome
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