Polymyalgia rheumatica.
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Biomedical subjects
Publications and source records attributed to P Macchioni.
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Polymyalgia rheumatica (PMR) is a common disorder of the elderly: the pathogenesis of the syndrome is still debated, though active synovitis of the shoulder has recently been confirmed. To investigate the pathogenesis of this synovitis we evaluated cell adhesion molecule (CAM) expression in shoulder synovial tissue from patients with PMR, correlated synovial expression with the serum levels of soluble forms, and assessed the changes associated with corticosteroid treatment. Arthroscopic synovial biopsies were obtained from 12 untreated and seven corticosteroid (CS)-treated cases. CAM expression was evaluated by MoAb staining on frozen sections and computerized image analysis. Soluble CAM were quantified by ELISA. Endothelial cells expressed intercellular adhesion molecule-1 (ICAM-1), E- and P-selectins. Infiltrating cells were ICAM-1 and beta1-integrin-positive, while L-selectin expression was limited to intravascular leucocytes. Synovial lining cells strongly expressed vascular cell adhesion molecule-1 (VCAM-1), and less intensely ICAM-1. Only the soluble form of ICAM-1 (sICAM-1) was elevated in untreated patients. CS treatment was associated with a decrease in ICAM-1, VCAM-1 and E- and P-selectin expression. sICAM-1 levels were in the normal range in treated patients. VLA-5 and 6 expression was widely distributed among cell types, and was not CS-sensitive. Active shoulder synovitis is associated with different CAM expression in PMR. ICAM-1 expression is widely distributed and correlates with elevated levels of the soluble form; it is significantly lower in CS-treated asymptomatic cases.
OBJECTIVE: To identify isolated peripheral enthesitis and/or dactylitis as a subset of psoriatic arthritis (PsA) and to define the clinical characteristics of these patients. METHODS: We examined 401 unselected patients with PsA seen in 3 Italian rheumatological centers over a 6 month period. The diagnosis of PsA was based upon the clinical experience of a rheumatologist. The clinical features of patients with PsA were assessed by clinical examination and review of the patients' charts, evaluating the presence of peripheral arthritis, spinal involvement, dactylitis, and enthesitis. A series of 483 rheumatological patients without psoriasis and spondyloarthropathy (European Spondylarthropathy Study Group criteria) seen consecutively in a one month period constituted the control group. RESULTS: 14 patients (3.5%) presented isolated episodes of peripheral enthesitis and/or dactylitis. No patient developed peripheral arthritis and/or axial involvement during the followup period (median 30 mo; range 3-72 mo). 10/14 patients (71%) presented at least one episode of finger and/or toe dactylitis. 5 of these 10 patients (50%) had additional episodes of peripheral enthesitis (Achilles tendinitis, plantar fasciitis, and posterior tibial tendinitis). Episodes of Achilles tendinitis and/or plantar fasciitis were present in 8/14 patients (57%). 3 of these 8 patients (37%) had associated peripheral enthesitis in other sites as well: lateral epicondyle, insertion of the patella tendon into the inferior pole of the patella, femoral quadriceps, and posterior tibial tendons. An additional case had posterior tibial tendinitis and 2 episodes of toe dactylitis. None of these 14 cases presented radiological evidence of sacroiliitis and only one of the 13 typed was HLA-B27 positive. 12 patients (2.4%) of the control group had episodes of peripheral enthesitis (11 plantar fasciitis and one Achilles tendinitis). No patient had episodes of dactylitis. The frequency of isolated Achilles tendinitis and/or dactylitis was significantly higher in patients with PsA compared to controls (3.5 vs 0.2%; p = 0.001). CONCLUSION: In some patients PsA can occur only with peripheral enthesitis, particularly Achilles tendinitis, and/or dactylitis. These patients may represent a subset of PsA, not defined by Moll and Wright and spondyloarthritis classification criteria, and poorly recognized in the studies on PsA.
OBJECTIVE: To investigate the immunologic features of synovitis in patients with polymyalgia rheumatica (PMR) and to assess the modifications induced by corticosteroids. METHODS: Arthroscopic biopsies of shoulder synovium were obtained from 12 patients with untreated PMR and from 7 patients with PMR that had been treated. Immunohistochemistry was performed on frozen sections utilizing a panel of monoclonal antibodies and computerized image analysis. RESULTS: Synovitis was present in 10 of 12 (83%) untreated patients and in only 2 of 7 (29%) treated patients. The synovitis was characterized by vascular proliferation and leukocyte infiltration. Infiltrating cells consisted predominantly of macrophages and T Lymphocytes. Almost all T lymphocytes were CD45RO positive. A few neutrophils, but no B cells, natural killer cells, or gamma/delta T cells were found. Intense expression of HLA class II antigens (DR moreso than DP moreso than DQ) was found in the lining layer cells as well as in macrophages and lymphocytes. DR, but not DP or DQ, was expressed by the endothelium of a few vessels. Class II antigen expression correlated with the number of macrophages and lymphocytes. Macrophage infiltration of arteriole walls was observed in 1 untreated patient without giant cell arteritis (GCA). In untreated patients, there was a positive correlation between the percentage of infiltrating T cells and the duration of disease. Steroid therapy was associated with a significant reduction in the number of blood vessels and of HLA class II expression. One treated patient who no longer had symptoms of PMR still had active synovitis: a relapse occurred 4 months after the biopsy. CONCLUSION: Our findings support the hypothesis that synovitis is a major cause of the musculoskeletal symptoms of PMR. There are immunologic similarities with the vascular inflammation observed in GCA. Corticosteroids act on both the vascular and cellular components of synovitis.
OBJECTIVE: To investigate the effects of desferrioxamine (DFO) infusion on chronic disease anemia (CDA) of rheumatoid arthritis (RA) by evaluating interleukin-6 (IL-6) and erythropoietin (EPO) production. PATIENTS AND METHODS: Five patients with RA and CDA (group I) were treated with DFO, 500 mg daily, through a continuous 10-h subcutaneous infusion 5 days a week for 4 weeks. One month after withdrawal, DFO was resumed in all five group I patients (group II) with an increase to 1 g daily following the previous treatment schedule. Clinical and laboratory parameters were evaluated weekly during the two study periods. Serum EPO was measured by radioimmunoassay. IL-6 was detected by the enzyme-linked immunoabsorbent assay method. RESULTS: No significant variations in hematological parameters, IL-6 or EPO levels were observed in group I patients. After 1 week of DFO 1 g daily, reticulocyte counts and EPO improved significantly. Hemoglobin and hematocrit rose significantly after 3 weeks of 1 g daily DFO therapy. Four weeks after DFO withdrawal, EPO, reticulocyte counts, hemoglobin and hematocrit returned to baseline levels. A significant improvement in the clinical parameters of disease activity was observed, particularly in group II patients. CONCLUSION: DFO improves CDA in RA patients. The beneficial effects on erythropoiesis seem to be related to improved EPO responsiveness to the anemia.
The aim of this study was to evaluate CD8 lymphocyte subsets in active polymyalgia rheumatica (PMR), to determine whether low percentages of CD8+ cells could be used to differentiate PMR from elderly-onset (EORA) and adult rheumatoid arthritis (RA), and to investigate the effects of prednisone on CD8 lymphocyte subsets. A significant reduction of percentages and absolute numbers of CD8bright+ cells was observed in patients with active PMR. Both CD8bright+, CD57- and CD8bright+, CD57+ subsets were significantly reduced. Reduced percentages of CD8+ cells were observed in 55% of patients with active PMR/giant cell arteritis (GCA), in 23% with EORA and in 44% with adult RA. Prednisone therapy in PMR patients, after only 1 week, increased the lymphocyte count and the absolute numbers of lymphocyte subsets significantly. However, the percentages of CD8bright+ cells remained persistently low for the 2 yr study period in 80% of the patients with low pre-treatment levels. Our results demonstrate that CD8 cell percentage is a poor epidemiological discriminator for PMR diagnosis. Notwithstanding the rise in absolute numbers of CD8 cell subsets induced by prednisone, the persistently low percentages of CD8+ cells in a group of PMR patients indicate an abnormality connected with the disease.
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OBJECTIVES: To determine if the presence of low percentages of CD8 positive cells or high levels of soluble interleukin-2 receptors (sIL-2R) define a subgroup of patients with more severe polymyalgia rheumatica and giant cell arteritis (PMR/GCA). METHODS: 38 PMR/GCA patients were followed up prospectively. Serum levels of sIL-2R and peripheral blood CD8 lymphocytes were measured before the start of corticosteroid treatment, after six months of treatment and at the last visit. Phenotypical analysis of lymphocyte subpopulations was performed with a two colour technique, and assay of sIL-2R was performed using an enzyme-linked immunosorbent kit. Forty four healthy people matched for age and gender comprised a healthy control group. RESULTS: The median duration of follow up was 28 months (range 7-65). Corticosteroid treatment lasted a median of 23.5 months (7-65). Eleven patients (29%) were in remission at the end of follow up; 45% of the patients had at least one relapse or recurrence. Compared with controls, patients with active disease had a significantly lower percentage of CD8 cells and significantly increased sIL-2R levels. Erythrocyte sedimentation rate, C reactive protein, and sIL-2R values were significantly less after six months of steroid treatment compared with before treatment. The percentage of CD8 cells remained significantly lower at six months and the end of follow up compared with controls, while sIL-2R levels remained significantly greater. Patients in whom the percentage of CD8 cells at six months was lower than one SD of the mean of normal controls (26%) had a significantly longer duration of corticosteroid treatment, a greater cumulative dose of prednisone and more relapses or recurrences compared with patients in whom the percentage was in the normal range. The duration of treatment and the cumulative dose of prednisone were not influenced by the percentage of CD8 cells before treatment therapy or by the levels of sIL-2R after six months of treatment. CONCLUSIONS: A reduced percentage of CD8 cells after six months of treatment may be a useful outcome parameter which would identify a group of PMR/GCA patients likely to experience more severe disease, defined as longer duration of corticosteroid treatment, higher cumulative dose of prednisone, and relapse or recurrence of disease.
OBJECTIVE: To evaluate the prevalence of psoriatic arthritis (PsA) in Italian patients with psoriasis and to compare the Moll and Wright criteria, the European Spondylarthropathy Study Group (ESSG) criteria, and Amor criteria when applied to this patient population. METHODS: We examined 205 unselected patients with psoriasis. The diagnosis of PsA was based upon the clinical experience of a rheumatologist. After, we tested these classification criteria. HLA class I and II antigens were also analyzed. RESULTS: Thirty-six percent (75) of psoriatic patients were considered by a clinical expert to have PsA. Moll and Wright criteria identified 46 patients (22%) with PsA; 49 patients (24%) were identified by ESSG criteria and Amor criteria; 12 patients identified by Amor criteria but not by ESSG criteria presented enthesitis or dactylitis; 10 patients identified by ESSG but not by Amor criteria had peripheral synovitis. In patients with peripheral arthritis and psoriasis, the evaluation of NSAID response was critical to fulfilling Amor criteria. However, it was not easy to retrospectively evaluate NSAID response using these criteria. The sensitivity was low for each of the 3 classification criteria (from 61 to 65%), whereas the specificity was high (from 99 to 100%). CONCLUSION: Our study confirms a high prevalence of PsA among an unselected population of Italian patients with psoriasis. Our data reveal the inadequacy of the existing criteria for PsA, including the ESSG criteria and Amor criteria for the classification of spondyloarthropathy.
OBJECTIVE: To determine the levels of serum soluble intercellular adhesion molecule 1 (sICAM-1) in patients with polymyalgia rheumatica (PMR) and/or giant cell arteritis (GCA) prior and during steroid therapy. METHODS: Sixteen patients with PMR and/or GCA had complete clinical and laboratory investigations at diagnosis before treatment and 9 patients were followed during 6 months of steroid therapy. Serum sICAM-1 levels were measured by ELISA: RESULTS: Serum ICAM-1 levels were higher in the patient group compared to a control population. No significant correlation was found between serum sICAM-1 levels and other indices of disease activity. After steroid administration, a dramatic fall in serum sICAM-1 levels was observed at the end of the first week and persisted until the end of the study period, paralleling clinical and laboratory disease remission. CONCLUSION: Serum sICAM-1 levels paralleled disease activity in PMR and/or GCA. Steroid treatment induced a rapid normalization of the serum sICAM-1 levels.
OBJECTIVE: Soluble CD4 (sCD4) and sCD8 were measured in the sera of 19 patients with active polymyalgia rheumatica (PMR). METHODS: We correlated the results obtained with lymphocyte subpopulations, soluble interleukin 2 receptors (sIL-2R), and clinical and laboratory variables at diagnosis. In addition 15 patients were prospectively studied during a 6 month period of prednisone therapy. Assays of the sCD4 and sCD8 molecules and of the sIL-2R were performed using an enzyme-linked immunosorbent kit. RESULTS: Serum sCD8 and sIL-2R levels were significantly elevated in patients with active disease compared to normal controls, while serum sCD4 and the relative percentage of CD8+ T cell levels decreased. In the 15 patients prospectively studied sCD8 levels fell significantly after 1 week of therapy along with the remission of clinical disease and normalization of erythrocyte sedimentation rate. At the end of the study period, sCD8 values did not differ from normal controls and they were significantly reduced compared to baseline values. CD8+ lymphopenia persisted at the end of the study. sCD4 levels remained significantly lower during the study period. sIL-2R levels fell significantly at the end of the study period. However, the 6-month levels of sIL-2R remained significantly higher compared to controls. CONCLUSION: The rise of serum sCD8 levels observed in patients with PMR with active disease suggests an early activation of CD8 T cells. The therapeutic effect of steroid in PMR may be partially mediated by its effect on CD8 activated cells.
The phenotypic characteristics of peripheral blood lymphocytes were investigated in 22 patients suffering from active polymyalgia rheumatica/giant cell arteritis (PMR/GCA) prior to steroid treatment. We observed a significant reduction in the absolute number and the relative percentage of CD4-, CD8+ and CD3+, CD16+ and/or CD56+ cells compared to controls. Fifteen patients were investigated prospectively over a 6-month period of prednisone therapy. At the end of the study CD4-CD8+ cells had increased significantly compared to baselines, CD3+ CD16+ and/or CD56+ cells remained significantly lower when compared to controls. We did not observe any abnormalities in the absolute number and percentage of HLA-DR+ T lymphocytes, CD5+ B cells and NK cell phenotypes before or during steroid treatment. Our study confirms that there was significant increase in the absolute number of CD8+ T cells during steroid treatment in the PMR/GCA patients, but indicates the persistence of an immunological alteration despite the control of disease manifestations.
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The radiological changes of the cervical spine were evaluated in 57 patients with psoriatic arthritis and were correlated with clinical, radiological, and immunogenetic features of the disease. Forty patients (70%) showed radiological evidence of the cervical spine being affected by the disease. Two patterns of cervical spine abnormalities were noted. Fifteen patients (26%) had erosive and/or subluxing cervical rheumatoid like lesions; 25 patients (44%) had a more frequently reported pattern similar to ankylosing spondylitis. Although subaxial subluxations were the most frequently observed cervical abnormalities (53%) in the inflammatory subgroup, none of the patients studied had cord compression. Ankylosing cervical spine disease was the only form of axial involvement in nine (36%) of 25 patients with the ankylosing form of psoriatic arthritis. All of these patients had peripheral disease and were B27 negative. Predictors of cervical spine disease patterns were considered using clinical, demographic, and radiological features and HLA antigens. The results of a multivariate analysis showed that the best predictors of inflammatory cervical spine disease are the presence of HLA-B39 and HLA-DR4 antigens, radiocarpal erosions, and the absence of the HLA-DR5 antigen.
Twelve patients with psoriatic arthritis (PsA) and very active articular disease resistant to conventional second line therapy entered into a 6-month open study of cyclosporine A (CsA) at a starting dosage of 3 mg/kg/day. Comparisons of phenotypic characteristics of lymphocytes and response to mitogens of peripheral blood mononuclear cells (PBMC) were made between these patients with PsA before CsA therapy, 7 patients without prior 2nd line therapy, 14 untreated patients with psoriasis alone, and 61 healthy controls. We confirmed a significant reduction of the basal percentage of CD8+ cells and an increase in the CD4/CD8 ratio in patients with PsA before CsA therapy compared to controls. These abnormalities were not present in patients with PsA without prior 2nd line therapy and in patients with psoriasis alone. Peripheral blood activated T cells (CD3+, HLA-DR+), natural killer (NK) (CD3-, CD16+ and/or CD56+), total B and CD5+ B cells were decreased only in patients with PsA before CsA therapy. The reduction of non-MHC restricted cytotoxicity T (CD3+, CD16+ and/or CD56+) was observed in all the 3 groups of patients compared to controls. After the 6 months of CsA therapy we observed a significant increase of CD3+, HLA-DR+, CD3+, CD16+ and/or CD56+, total B, and CD20+, CD5+ cells in the 11 patients with PsA compared to pretreatment values. Contrary to azathioprine, CsA does not impair the NK cell population which has a protective role against cancer and viral infections.