The challenge of the definition of early symptomatic knee osteoarthritis: a proposal of criteria and red flags from an international initiative promoted by the Italian Society for Rheumatology.

The aim of this study was to establish consensus for potential early symptomatic knee osteoarthritis (ESKOA) clinical definition and referral criteria from primary care to rheumatologists, based on available data from literature and a qualitative approach, in order to perform studies on patients fulfilling such criteria and to validate the obtained ESKOA definition. A complex methodological approach was followed including: (1) three focus groups (FG), including expert clinicians, researchers and patients; (2) a systematic literature review (SLR); (3) two discussion groups followed by a Delphi survey. FG and SLR were performed in parallel to inform discussion groups in order to identify relevant constructs to be included in the modified Delphi survey. ESKOA is defined in the presence of: (a) two mandatory symptoms (knee pain in the absence of any recent trauma or injury and very short joint stiffness, lasting for less than 10 min, when starting movement) even in the absence of risk factors, or (b) knee pain, and 1 or 2 risk factors or (c) three or more risk factors in the presence of at least one mandatory symptom, with symptoms lasting less than 6 months. These criteria are applicable in the absence of active inflammatory arthritis, generalized pain, Kellgren-Lawrence grade >0, any recent knee trauma or injury, and age lower than 40 years. Knee pain in the absence of any recent trauma lasting for less than 6 months was considered as the referral criterion to the rheumatologist for the suspicion of ESKOA. This consensus process has identified provisional clinical definition of ESKOA and defined potential referral criterion to rheumatologist, in order to test ESKOA obtained definition in prospective validation studies.

Color duplex ultrasonography findings of temporal arteries in a case of giant cell arteritis: role in diagnosis and follow-up.

Giant cell arteritis (GCA) is a systemic autoimmune disease that affects medium- and large-sized arteries. The diagnostic gold standard is the temporal artery biopsy, but it has limited sensitivity and some difficulties in reproducibility. Color duplex ultrasonography is a noninvasive, reproducible, and inexpensive method for diagnosis of temporal arteries involvement (temporal arteritis [TA]) in GCA with high sensitivity and specificity. We present the ultrasound findings at baseline and during follow-up in a case of TA in a patient with GCA.

The macrophages in rheumatic diseases.

Macrophages belong to the innate immune system giving us protection against pathogens. However it is known that they are also involved in rheumatic diseases. Activated macrophages have two different phenotypes related to different stimuli: M1 (classically activated) and M2 (alternatively activated). M1 macrophages release high levels of pro-inflammatory cytokines, reactive nitrogen and oxygen intermediates killing microorganisms and tumor cells; while M2 macrophages are involved in resolution of inflammation through phagocytosis of apoptotic neutrophils, reduced production of pro-inflammatory cytokines, and increased synthesis of mediators important in tissue remodeling, angiogenesis, and wound repair. The role of macrophages in the different rheumatic diseases is different according to their M1/M2 macrophages phenotype.

Calciphylaxis in a patient affected by rheumatoid arthritis, chronic renal failure, and hyperparathyroidism: a case report.

Calciphylaxis, or calcific uremic arteriolopathy, is the tissue and vascular calcification that occurs mainly in chronic kidney disease. However, it can be secondary to parathyroid dysfunction and it has been described in rheumatic patients. We present a case of calciphylaxis in a woman with inactive rheumatoid arthritis, acute renal failure, and hyperparathyroidism.

User preference for a portable syringe pump for iloprost infusion.

PURPOSE: Administration of intravenous iloprost - a first-line European League Against Rheumatism (EULAR)-recommended choice for the treatment of scleroderma (SSc)-related digital vasculopathy - requires repeated treatment cycles of 6 hours per day in a hospital setting. During the infusion, patient mobility is considerably restricted due to the size and fixity of traditional syringe pumps. The aim of this study was to evaluate the satisfaction level of patients and nurses, after the introduction of a new portable syringe pump (Infonde(®), Italfarmaco S.p.A., Milan, Italy) at the Department of Rheumatology, Magenta Hospital, Milan, Italy. PATIENTS AND METHODS: Thirty-four consecutive SSc patients receiving stable therapy with iloprost, previously administered with a fixed pump, were treated using the portable Infonde(®) pump. Patients (n=34) and nurses (n=4) were asked to answer a nine- and six-item questionnaire, respectively, to assess the satisfaction of the administration comparing the new device versus the previous one. The health care staff of the ward developed the questionnaire, and the response scores ranged from 0 (fixed device better) to 10 (portable device better); thus a score >5 indicates a preference for Infonde(®). RESULTS: Patients' answers indicated a preference towards the new portable syringe pump, versus the previous fixed pump. Questionnaires administered to patients generated a total of 306 responses, with over 95% of the responses in the range 8-10, of which 89% had a score equal to 10. The responses of nurses showed a score equal to 10 in 100% cases. No significant adverse events were recorded, indicating no change in the tolerability profile of the drug. CONCLUSION: Iloprost administration with Infonde(®) pump was preferred by both patients and health care professionals, and was well tolerated. The possibility to perform daily activities and the freedom of movement suggest a positive impact of Infonde(®) on the treatment, with a potential favorable effect on the quality of life of patients during the many hours spent receiving the infusion.

Different T cells' distribution and activation degree of Th17 CD4+ cells in peripheral blood in patients with osteoarthritis, rheumatoid arthritis, and healthy donors: preliminary results of the MAGENTA CLICAO study.

OBJECTIVE: To determine distribution of T cells and activation degree of Th CD4+ cells in peripheral blood of patients with osteoarthritis (OA), rheumatoid arthritis (RA), and healthy donors. METHODS: Patients with established diagnosis of RA according to American College of Rheumatology/European League Against Rheumatism 2010 criteria, knee or hip OA according to American College of Rheumatology criteria, and healthy blood donor volunteers were eligible. Multi-channel flow cytometry and monoclonal antibodies against CD3, CD4, CD8, CCR6, CD38, CXCR3, and HLA DR were used to distinguish and evaluate T cells' subpopulation. RESULTS: We analyzed blood samples of 15 patients with well-defined RA, 56 with hip or knee OA, and 20 healthy age matched controls. Blood samples from RA patients showed significantly higher counts of CD4+ CD38+ DR+ (activated CD4 T cells) and Th17 (CCR6+ CXCR3-) cells as compared to OA patients and control group (P<0.01). Furthermore the samples from the OA patients showed a higher percentage of activated CD4 T cells and Th17 cells as compared to control group (P<0.05). Interestingly there was no difference between Th1 (CD4+ CXCR3+ CCR6-) and Th2 (CD4+ CXCR3- CCR6-) between the three groups (P>0.1). CONCLUSION: According to the latest view of OA disease pathogenesis, our preliminary results support the hypothesis that OA may also be a disease with an immunological/inflammatory involvement like RA. It seems that there is a quantitative but non-qualitative difference in Th17 cells' profile, including the expression of activation markers, between RA and OA.

Successful treatment of a patient with giant cell vasculitis (horton arteritis) with tocilizumab a humanized anti-interleukin-6 receptor antibody.

Giant cell arteritis (GCA) is the most common form of systemic vasculitis in adults, affecting preferentially medium-large size arteries. Here we report a case of a female with a diagnosis of GCA based on temporal artery biopsy, successfully treated with tocilizumab, a humanized anti-interleukin-6 receptor antibody.

NK cell count as predictor of clinical response in patients with rheumatoid arthritis treated with rituximab.

PURPOSE: The relationship between antiCD20 therapy with rituximab and the lymphocytes phenotype in patients with rheumatoid arthritis was investigated, with an attempt to establish a relationship between commonly used clinical activity indices and variations in leukocyte count, in particular natural killer (NK) lymphocytes. METHODS: Patients with seropositive (cyclic citrullinated peptides and rheumatoid factor positive) rheumatoid arthritis (according to the American College of Rheumatology 1987 criteria) refractory to conventional and antitumor necrosis factor-alpha agents who were subsequently treated with rituximab, a chimeric monoclonal antibody directed against CD20, were enrolled between January 2009 and September 2009. All subjects were treated with rituximab standard rheumatologic dose of 1.0 g on days 1 and 15 every 6 months for at least 2 years. A clinical evaluation was performed at baseline and subsequently every 3 months thereafter. At each assessment activated NK (CD56+/CD16+/CD54bright) cell count was collected and disease activity was assessed using Disease Activity Score in 28 Joints and the Simplified Disease Activity Index (SDAI). RESULTS: Thirty-four patients were enrolled (mean age ± standard deviation: 54.8 ± 12.8 years). Basal SDAI was 21.75 ± 5.4 and NK cell count mean value was 157.6 ± 90. After 24 months, SDAI was 14 ± 1.2 and NK cell count mean value was 301.7 ± 21 (P < 0.05). An inverted correlation between SDAI and NK count was observed at 3 months (r = -0.36, P < 0.05), 6 months (r = -0.48, P < 0.45), 9 months (r = -0.47, P < 0.05), 12 months (r = -0.41, P < 0.01), 15 months (r = -0.58, P < 0.05), 18 months (r = -0.53, P < 0.05), 21 months (r = -0.68, P < 0.05), and 24 months (r = -0.61, P < 0.05). A linear regression model between all variables collected and SDAI/Disease Activity Score in 28 Joints at 6 months and 12 months confirmed a significant relationship between SDAI/Disease Activity Score in 28 Joints and NK cell count. CONCLUSION: The data confirm the clinical efficacy of rituximab and suggests the use of NK cells as a predictor of clinical response in patients with rheumatoid arthritis.

Safety of etanercept in elderly subjects with rheumatoid arthritis.

OBJECTIVE: To report side effects seen in a clinical cohort of patients aged >65 years with rheumatoid arthritis (RA) treated with the tumor necrosis factor-alpha TNF-alpha blocker etanercept and to compare the side effects rate with patients aged 65 years and 62 (40 females, 22 males) aged <65 years. In the patients aged >65 years, the safety profile (defined as rate of side effects) of etanercept was similar to that in patients aged 0.05) and the survival curves between the groups were similar (P > 0.05). CONCLUSIONS: In our three-year experience, the anti-TNFalpha agent etanercept has been well tolerated and safe in elderly patients. The risk of side effects in these patients was no greater than in subjects aged

An open, randomized comparison study of cyclosporine A, cyclosporine A + methotrexate and cyclosporine A + hydroxychloroquine in the treatment of early severe rheumatoid arthritis.

PURPOSE: To determine whether a regimen of cyclosporine (CSA) and methotrexate (MTX), or CSA and hydroxychloroquine (HCQ) introduced in early rheumatoid arthritis (RA) can produce a significant improvement in clinical outcome and/or retard radiographic damage in comparison with standard monotherapy with CSA alone. METHODS: One hundred five patients with active RA of less than 36 months duration, who had never previously been treated with immunosuppressive agents, were included in a 12-month, multi-center, open, randomized trial. Patients who fulfilled the criteria for early severe RA were randomized to receive either combination therapy (CSA + MTX n = 34, CSA + HCQ n = 35) or CSA alone (n = 36). RESULTS: CSA + MTX was more effective than the other two treatment groups in controlling RA symptoms. CSA+MTX did not show a significant radiographic progression according to Larsen-Dale (0.90 +/- 3.89 compared to baseline values, P > 0.05); moreover, patients treated with CSA alone or CSA+HCQ showed a significant worsening of Larsen-Dale score (2.91 +/- 5.99 and 2.97 +/- 4.28 respectively vs baseline values, P < 0.05), although not significant when compared with the CSA + HCQ group (P = 0.56 and 0.39, respectively). CONCLUSIONS: This trial indicated that CSA+MTX was more effective than the other two treatments in improving clinical data and inhibiting radiographic progression, although the differences were not significant in this relatively small study. However, the difference was significant in favor of CSA + MTX regarding ACR 50% response.