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To compare the efficacy and safety of TCZ in monotherapy (TCZ MONO) vs. combined with conventional immunosuppressive drugs (TCZ COMBO) in Giant Cell Arteritis (GCA) in a clinical practice scenario. Multicenter study of 134 patients with refractory GCA. Patients on TCZ MONO (n = 82) were compared with those on TCZ COMBO (n = 52). Drugs were methotrexate (MTX) (n = 48), azathioprine (n = 3), and leflunomide (n = 1). The main outcomes were: prolonged remission (normalization of clinical and laboratory parameters for at least 6 months) and the number of relapses. Patients on TCZ COMBO were younger (68.8 ± 8.0 vs 71.2 ± 9.0 years; p = 0.04), with a trend to a longer GCA duration (median [IQR],18.5 [6.25–34.0] vs. 13.0 [7.75–33.5] months; p = 0.333), higher C-reactive protein (CRP) levels (2.1[1–4.7] vs 1.2 [0.2–2.4] mg/dL; p = 0.003), and more prevalence of extra-cranial large-vessel vasculitis (LVV) (57% vs. 34.1%; p = 0.007). In both groups, rapid and sustained improvement was observed. Despite the longer GCA duration, and the higher CRP levels and prevalence of LVV in the TCZ COMBO , the improvement was similar in both groups at 12 months. Moreover, in the TCZ COMBO group, prolonged remission was significantly higher at 12-month. Relapses and serious adverse events were similar in both groups. In clinical practice, TCZ in monotherapy or combined with conventional immunosuppressive agents is effective and safe in patients with GCA. Nevertheless, the addition of immunosuppressive drugs, usually MTX, seems to allow a higher rate of prolonged remission, even in patients with a longer GCA duration, more extra-cranial LVV involvement, and higher acute-phase reactants. [ABSTRACT FROM AUTHOR]

• There is an unmet need for rescue therapies in patients with progressive RA-ILD who do not respond to csDMARDs or immunosuppressants. • RTX rescue therapy was able to reverse the decline of lung function parameters in a not negligible proportion of patients that develop a progressive fibrosing course • The use of RTX was well tolerated in the majority of patients. • RTX was associated with a high retention rate (around 74%) at the end of follow-up. To assess the real-world, long-term effectiveness of rituximab (RTX) as a rescue therapy in patients with progressive rheumatoid arthritis-related interstitial lung disease (RA-ILD) in whom more conventional therapy has failed. Longitudinal retrospective observational study of a cohort of patients with RA-ILD that started treatment with RTX due to ongoing progressive ILD despite treatment with glucocorticoids and csDMARDs or immunosuppressants (IS). All patients were treated with two or more cycles of RTX and evaluated for at least 12 months. Ongoing therapy with csDMARDs or IS remained unchanged. Thirty-one patients were analyzed. Before initiation of RTX the mean decline (delta) in %pFVC and %pDLCO from the ILD diagnosis (median 21 months) was -16.5% and -19.7%, respectively. After 1 year of treatment, RTX was able to reverse the decline of pulmonary function test (PFTs) parameters: ∆%pFVC +8.06% compared to baseline (95% CI: -10.9 to -5.2; p <0.001) and ∆%pDLCO +12.7% (95% CI: -16.3 to -9.1; p <0.001). In addition, there was a significant reduction in the median dose of prednisone, and it could be suspended in 26% of cases. Dividing the population into UIP and non-UIP patterns, we observed a significant increase in PFTs parameters in both groups. In the 25 patients (80.6%) that completed 2 years of treatment, the statistically significant amelioration in PFTs parameters observed at one year was maintained: ∆%pFVC +11.2% (95% CI: -15.6 to -6.8; p <0.001) and ∆%pDLCO +14.8% (95% CI: -19.3 to -10.3; p <0.001). At the end of the follow-up period (median 32 months; IQR 25th–75th 26–64), only 23 of the 31 patients (74.2%) were still undergoing treatment with RTX: in 3 cases (10%) it was stopped due to adverse events, in another 3 (10%) treatment failed ultimately requiring a lung transplant, and 2 patients (6%) died due to progression of the ILD and infectious complications. The frequency of adverse events reached 32% of cases. Based on our results, RTX appears to be effective as rescue therapy in a considerable proportion of patients with progressive RA-ILD unresponsive to conventional treatment. [ABSTRACT FROM AUTHOR]

• There is an unmet need for rescue therapies in patients with progressive SSc-ILD who do not respond to conventional immunosuppressants. • The combination of MMF/RTX was able to reverse the decline of lung function parameters in a not negligible proportion of patients with a progressive fibrosing phenotype, unresponsive to conventional therapy. • Rituximab has a reasonable safety profile. To test whether the use of rituximab (RTX) is effective and safe as a rescue therapy add-on treatment to mycophenolate (MMF) in patients with progressive systemic sclerosis-associated interstitial lung disease (SSc-ILD) in whom conventional immunosuppressants (IS) have failed. Longitudinal retrospective observational study of a cohort of patients with SSc-ILD that started treatment with RTX due to ongoing lung function impairment despite treatment with glucocorticoids and IS (cyclophosphamide and/or MMF). All patients were treated with 2 or more cycles of RTX and evaluated for at least 12 months. Twenty-four patients were included. Before initiation of RTX the mean decline in%pFVC and %pDLCO during the previous 2 years (delta) was −12.9% and −12.5%, respectively. After 1 year of treatment with RTX, a significant improvement in %pFVC (∆+8.8% compared to baseline, 95% CI: −13.7 to −3.9; p = 0.001) and%pDLCO (∆+4.6%, 95% CI: −8.2 to −0.8; p = 0.018) was observed. In addition, there was a significant reduction in the median dose of prednisone and it could be suspended in 25% of patients. At 2 years of treatment, RTX had been discontinued in 9 patients (due to adverse events in 3 cases and inefficacy in 6). In the 15 patients (62.5%) that completed 24 months of therapy, the statistically significant amelioration in pulmonary function test parameters was maintained: ∆%pFVC: +11.1% (95% CI: −17.6 to −4.5; p = 0.003) and ∆%pDLCO: +8.7% (95% CI: −13.9 to −8.3; p = 0.003). Based on our results, RTX's use as an add-on treatment to MMF appears to be effective as a rescue therapy in patients with a more aggressive SSc-ILD phenotype. [ABSTRACT FROM AUTHOR]

To investigate the prevalence, clinical characteristics and prognosis of pulmonary arterial hypertension (PAH) in adult onset Still's disease (AOSD). We retrospectively reviewed all patients with AOSD diagnosed during a 33-year period in 2 referral tertiary care hospitals, selecting for analysis those who presented PAH confirmed as by right heart catheterization. A systematic review of the literature (PubMed 1990 to July 2018) was also performed, in order to determine the prognosis and the most appropriate treatment strategy for this complication. The overall prevalence of PAH in our AOSD population was 4.8% (2/41). Including our 2 cases, 20 well-documented patients have been reported. PAH may complicate AOSD at any time during its course, and usually occurs in patients who have persistent and severe disease, with a considerable frequency (35%) of previous or concomitant severe clinical complications. In all cases, the etiology of pulmonary hypertension was a group 1 PAH based on the 2015 ESC/ERS guidelines. Most patients in this series had advanced WHO functional classes III-IV at the time of PAH diagnosis, reflecting an important diagnostic delay. Thirty-three percent of patients had a poor outcome despite the therapy, with a mortality rate that reached 22%. The therapeutic strategy that achieved the best results was the use of glucocorticoids, immunosuppression and PAH-specific vasodilator therapy. HAP is an under-recognized complication of AOSD that should be kept in mind in the differential diagnosis of those patients who experience dyspnea on exertion or a decrease in exercise tolerance [ABSTRACT FROM AUTHOR]

Objective: Tocilizumab (TCZ) has shown efficacy in clinical trials on giant cell arteritis (GCA). Real-world data are scarce. Our objective was to assess efficacy and safety of TCZ in unselected patients with GCA in clinical practice Methods: Observational, open-label multicenter study from 40 national referral centers of GCA patients treated with TCZ due to inefficacy or adverse events of previous therapy. Outcomes variables were improvement of clinical features, acute phase reactants, glucocorticoid-sparing effect, prolonged remission and relapses. A comparative study was performed: (a) TCZ route (SC vs. IV); (b) GCA duration (≤6 vs. >6 months); (c) serious infections (with or without); (d) ≤15 vs. >15 mg/day at TCZ onset. Results: 134 patients; mean age, 73.0 ± 8.8 years. TCZ was started after a median [IQR] time from GCA diagnosis of 13.5 [5.0–33.5] months. Ninety-eight (73.1%) patients had received immunosuppressive agents. After 1 month of TCZ 93.9% experienced clinical improvement. Reduction of CRP from 1.7 [0.4–3.2] to 0.11 [0.05–0.5] mg/dL (p < 0.0001), ESR from 33 [14.5–61] to 6 [2–12] mm/1st hour (p < 0.0001) and decrease in patients with anemia from 16.4% to 3.8% (p < 0.0001) were observed. Regardless of administration route or disease duration, clinical improvement leading to remission at 6, 12, 18, 24 months was observed in 55.5%, 70.4%, 69.2% and 90% of patients. Most relevant adverse side-effect was serious infections (10.6/100 patients-year), associated with higher doses of prednisone during the first three months of therapy. Conclusion: In clinical practice, TCZ yields a rapid and maintained improvement of refractory GCA. Serious infections appear to be higher than in clinical trials. [ABSTRACT FROM AUTHOR]

Obstetric complications are more common in women with systemic lupus erythematosus (SLE) than in the general population. To assess pregnancy outcomes in women with SLE from the RELESSER cohort after 12 years of follow-up. A multicentre retrospective observational study was conducted. In addition to data from the RELESSER register, data were collected on obstetric/gynaecological variables and treatments received. The number of term pregnancies was compared between women with pregnancies before and after the diagnosis of SLE. Further, clinical and laboratory characteristics were compared between women with pregnancies before and after the diagnosis, on the one hand, and with and without complications during pregnancy, on the other. Bivariate and multivariate analyses were carried out to identify factors potentially associated with complications during pregnancy. A total of 809 women were included, with 1869 pregnancies, of which 1395 reached term. Women with pregnancies before the diagnosis of SLE had more pregnancies (2.37 vs 1.87) and a higher rate of term pregnancies (76.8% vs 69.8%, p < 0.001) compared to those with pregnancies after the diagnosis. Women with pregnancies before the diagnosis were diagnosed at an older age (43.4 vs 34.1 years) and had more comorbidities. No differences were observed between the groups with pregnancies before and after diagnosis in antibody profile, including anti-dsDNA, anti-Sm, anti-Ro, anti-La, lupus anticoagulant, anticardiolipin or anti-beta-2-glycoprotein. Overall, 114 out of the 809 women included in the study experienced complications during pregnancy, including miscarriage, preeclampsia/eclampsia, foetal death, and/or preterm birth. Women with complications had higher rates of antiphospholipid syndrome (40.5% vs 9.9%, p < 0.001) and higher rates of positivity for IgG anticardiolipin (33.9% vs 21.3%, p = 0.005), IgG anti-beta 2 glycoprotein (26.1% vs 14%, p = 0.007), and IgM anti-beta 2 glycoprotein (26.1% vs 16%, p = 0.032) antibodies, although no differences were found regarding lupus anticoagulant. Among the treatments received, only heparin was more commonly used by women with pregnancy complications. We did not find differences in corticosteroid or hydroxychloroquine use. The likelihood of term pregnancy is higher before the diagnosis of SLE. In our cohort, positivity for anticardiolipin IgG and anti-beta-2- glycoprotein IgG/IgM, but not lupus anticoagulant, was associated with a higher risk of poorer pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Objectives To estimate the incidence of severe infection and investigate the associated factors and clinical impact in a large systemic lupus erythematosus (SLE) retrospective cohort. Methods All patients in the Spanish Rheumatology Society Lupus Registry (RELESSER) who meet ≥4 ACR-97 SLE criteria were retrospectively investigated for severe infections. Patients with and without infections were compared in terms of SLE severity, damage, comorbidities, and demographic characteristics. A multivariable Cox regression model was built to calculate hazard ratios (HRs) for the first infection. Results A total of 3658 SLE patients were included: 90% female, median age 32.9 years (DQ 9.7), and mean follow-up (months) 120.2 (±87.6). A total of 705 (19.3%) patients suffered ≥1 severe infection. Total severe infections recorded in these patients numbered 1227. The incidence rate was 29.2 (95% CI: 27.6–30.9) infections per 1000 patient years. Time from first infection to second infection was significantly shorter than time from diagnosis to first infection ( p < 0.000). Although respiratory infections were the most common (35.5%), bloodstream infections were the most frequent cause of mortality by infection (42.0%). In the Cox regression analysis, the following were all associated with infection: age at diagnosis (HR = 1.016, 95% CI: 1.009–1.023), Latin-American (Amerindian-Mestizo) ethnicity (HR = 2.151, 95% CI: 1.539–3.005), corticosteroids (≥10 mg/day) (HR = 1.271, 95% CI: 1.034–1.561), immunosuppressors (HR = 1.348, 95% CI: 1.079–1.684), hospitalization by SLE (HR = 2.567, 95% CI: 1.905–3.459), Katz severity index (HR = 1.160, 95% CI: 1.105–1.217), SLICC/ACR damage index (HR = 1.069, 95% CI: 1.031–1.108), and smoking (HR = 1.332, 95% CI: 1.121–1.583). Duration of antimalarial use (months) proved protective (HR = 0.998, 95% CI: 0.997–0.999). Conclusions Severe infection constitutes a predictor of poor prognosis in SLE patients, is more common in Latin-Americans and is associated with age, previous infection, and smoking. Antimalarials exerted a protective effect. [ABSTRACT FROM AUTHOR]

The search for new glucocorticoid-sparing disease-modifying anti-rheumatic drugs continues to be an unmet need in large vessel vasculitis (LVV). This report aims to assess the effectiveness and safety of leflunomide (LEF) in Takayasu arteritis (TA) and giant cell arteritis (GCA). We systematically reviewed the literature, searching for studies evaluating the efficacy of LEF in LVV. A meta-analysis was conducted using the random-effects method. The literature search identified eight studies that assessed LEF in TAK and seven in GCA. All were uncontrolled observational studies with a high risk of bias, implying a low or very-low certainty of evidence. In TAK, the pooled proportion of patients achieving at least a partial remission was 75% (95% CI: 0.64–0.84), angiographic stabilization was observed in 86% (0.77–0.94) and relapses in 12% (0.05–0.21). The mean reduction in the prednisolone dose (MRPD) after LEF treatment was 15.7 mg/d (10.28–21.16). Adverse events were observed in 8% of patients (0.02–0.16). Comparison of LEF with methotrexate (MTX) or cyclophosphamide revealed LEF to be superior in terms of remission induction, relapse prevention, and tolerance. When compared with tofacitinib, both drugs demonstrated comparable efficacy. In GCA, the pooled proportion of patients achieving at least a partial remission was 60% (0.17–0.95). The MRPD after LEF treatment was 15.63 mg/d (1.29–32.55) and 53% of the patients were able to discontinue glucocorticoids (0.25 – 0.80). Relapses were observed in 21% of cases (0.14– 0.28) and adverse events in 28% (0.12–0.46). Comparison of LEF with MTX showed similar efficacy and tolerance. LEF is well tolerated and might be effective for patients with TAK and GCA. [ABSTRACT FROM AUTHOR]

• Major CNS NP-SLE contributes to a 2-times higher mortality in SLE. • The individual major CNS NP-SLE manifestations contribute differently to survival in SLE. • CVD and organic brain syndrome are associated with the highest mortality rates. To analyze the prevalence, incidence, survival and contribution on mortality of major central nervous system (CNS) involvement in systemic lupus erythematosus (SLE). Patients fulfilling the SLE 1997 ACR classification criteria from the multicentre, retrospective RELESSER-TRANS (Spanish Society of Rheumatology Lupus Register) were included. Prevalence, incidence and survival rates of major CNS neuropsychiatric (NP)-SLE as a group and the individual NP manifestations cerebrovascular disease (CVD), seizure, psychosis, organic brain syndrome and transverse myelitis were calculated. Furthermore, the contribution of these manifestations on mortality was analysed in Cox regression models adjusted for confounders. A total of 3591 SLE patients were included. Of them, 412 (11.5%) developed a total of 522 major CNS NP-SLE manifestations. 61 patients (12%) with major CNS NP-SLE died. The annual mortality rate for patients with and without ever major CNS NP-SLE was 10.8% vs 3.8%, respectively. Individually, CVD (14%) and organic brain syndrome (15.5%) showed the highest mortality rates. The 10% mortality rate for patients with and without ever major CNS NP-SLE was reached after 12.3 vs 22.8 years, respectively. CVD (9.8 years) and organic brain syndrome (7.1 years) reached the 10% mortality rate earlier than other major CNS NP-SLE manifestations. Major CNS NP-SLE (HR 1.85, 1.29–2.67) and more specifically CVD (HR 2.17, 1.41–3.33) and organic brain syndrome (HR 2.11, 1.19–3.74) accounted as independent prognostic factors for poor survival. The presentation of major CNS NP-SLE during the disease course contributes to a higher mortality, which may differ depending on the individual NP manifestation. CVD and organic brain syndrome are associated with the highest mortality rates. [ABSTRACT FROM AUTHOR]

Objective To identify predictors of early response to tocilizumab (TCZ) in patients with active rheumatoid arthritis (RA) seen in daily routine clinical practice. Methods A multicenter ambispective observational study of 126 RA patients treated with TCZ as a first- or second-line biological therapy. The variables associated to achieve the therapeutic goal (remission defined as a DAS28-ESR < 2.6) at 3 and 6 months were identified using regression analysis. Results TCZ was administered as the first biologic in 26% of patients. Overall, 34% of patients received TCZ as monotherapy. EULAR response and remission were obtained in 82% and 31% of patients at 3 months and in 86% and 40% at 6 months. In the multivariate analysis, the predictive factors increasing the likelihood of clinical remission at 3 months were baseline ESR > 30 mm/h (OR = 19.07, 95% CI: 2.720–133.716), baseline CRP > 10 mg/L (OR = 4.95; 95% CI: 1.464–13.826), and the presence of extra-articular manifestations of the disease (OR = 15.45, 95% CI: 2.334–102.319). The factors that decreased it were higher concentrations of hemoglobin (OR = 0.53, 95% CI: 0.319–0.910), higher baseline DAS28-ESR (OR = 0.30, 95% CI: 0.145–0.635) and the number of previous DMARDs (OR = 0.41, 95% CI: 0.221–0.779), and biological therapies used (OR = 0.33, 95% CI: 0.155–0.734). The only factor that remained statistically significant at 6 months was higher baseline DAS28-ESR (OR = 0.55, 95% CI: 0.347–0.877). No relationship was found with the neutrophil count or with the RF or ACPA positivity. Conclusion In routine clinical practice, strong acute phase response, the presence of extra-articular manifestations, and the number of previous DMARDs and biological therapies used may help to identify patients who will have a rapid response to TCZ. However, it is likely that no parameter will predict response if taken separately. [ABSTRACT FROM AUTHOR]

Objective To investigate the frequency and type of giant cell arteritis (GCA)-related ischemic complications in a series of patients with GCA who, for a substantial period of time (i.e., at least 3 mo), lacked vascular symptoms and presented with apparently isolated polymyalgia rheumatica (PMR). Methods Retrospective follow-up study of an unselected population of 167 patients with GCA diagnosed from 1985 to 2014. Results In all, 18 patients (11%) developed GCA on a background of a prior history of PMR. They were diagnosed as having isolated PMR because they did not have clinical evidence of GCA at diagnosis and exhibited a prompt and complete response to low-dose steroid therapy. However, during the course of treatment, 17 patients later experienced an arteritic relapse with the development of typical craniofacial symptoms, and one patient developed signs of upper extremity vascular insufficiency, resulting in the diagnosis of large-vessel GCA. The median time to GCA diagnosis from the initiation of low-dose steroid therapy was 9 ± 14.4 mo (range: 3−39). At the time of GCA diagnosis, severe ischemic complications were observed in 50% (9/18) of the patients. Of these patients 22% (4/18) were considered to have “true” occlusive disease (i.e., permanent visual loss, stroke, and/or limb claudication). Late inflammation of the aorta and its branches occurred in 4 (22%) of the patients during long-term follow-up. Conclusion Patients with GCA presenting with apparently isolated PMR have a significant risk of developing transient or permanent disease-related ischemic complications; these complications occurred in 50% of the cases. [ABSTRACT FROM AUTHOR]

Objective To investigate the frequency, location, characteristics, and clinical significance of subaxial involvement (below C1–C2) in a series of patients with rheumatoid arthritis (RA) and symptomatic involvement of the cervical spine. Methods A total of 41 patients with RA were examined via cervical spine magnetic resonance imaging (MRI). A comparative analysis of the incidence of the different types of subaxial lesions was performed between these patients and 41 age- and sex-matched patients with symptomatic cervical spondylosis. Results Stenosis of the spinal canal was found at the subaxial level in 85% of RA patients, and at the atlantoaxial level in 44%. Comparative analysis between these patients and the cervical spondylosis patients revealed significant differences in the types and frequencies of subaxial lesions. For both conditions, signs of discopathy and end-plate osteophytosis were the most common abnormalities observed on magnetic resonance imaging (MRI). However, in the RA patients these abnormalities coincided with subchondral bone and ligamentous acute inflammatory changes and with secondary destruction (vertebral instability) or repair (vertebral ankyloses). Only evidence of subaxial myelopathy was significantly associated with an increased risk of neurological dysfunction among the RA patients [Ranawat class II or III; P = 0.01; odds ratio (OR) = 11.43], although subaxial cord compression tended toward a significant association with the risk of neurological dysfunction ( P = 0.06; OR = 3.95). Conclusion Subaxial stenosis seems to be the consequence of both the inflammatory process and mechanical-degenerative changes. Despite its frequency, it was not usually related to the occurrence of myelopathy symptoms, not even in cases with MRI evidence of spinal cord compression. [ABSTRACT FROM AUTHOR]

Objective To analyze the clinical features, microbiological spectrum, diagnostic procedures and outcomes in native joint pyogenic arthritis among non-intravenous drug users. Methods We collected all microbiologically proved cases of infectious arthritis at our hospital between 1992 and 2013. Patients with prosthetic joint infection were excluded, as were patients with non-pyogenic arthritis and intravenous drug users. Results We identified 268 patients; the mean age was 61 ± 14.7 years and 62% were men. The incidence increased over the period of study. In 188 patients (70%), one or more underlying medical illnesses were found. The mean symptom duration was 8.9 ± 9.5 days. Globally, 311 affected joints were found, 232 (75%) involving peripheral joints and 79 (25%) axial joints. Staphylococci (55%) and Streptococci (29%) were the predominant microorganisms. Blood cultures were positive in 78% (173/223) of the cases. In 81 patients (30%), one or more concomitant infectious processes were found. Antimicrobial therapy was prescribed 4–8 weeks in most cases, and surgical drainage was performed in 65% of patients. Four patients relapsed and 23 (8%) died. Conclusions The prevalence of pyogenic native joint arthritis in non-intravenous drug users is increasing, frequently affecting old patients with underlying medical conditions. Although large joints are the most frequently compromised, the involvement of axial joints is a relevant feature that has not been recognized in other series. Staphylococci and Streptococci are the main causative agents. Bacteremia and concomitant infectious processes are frequent complications. Diagnostic delay and mortality continue to be important concerns. [ABSTRACT FROM AUTHOR]

Objective To assess the efficacy of tocilizumab (TCZ) in giant cell arteritis (GCA) patients with refractory disease and/or with unacceptable side effects due to corticosteroids. Methods A retrospective multicenter open-label study on 22 GCA patients treated with TCZ at standard dose of 8 mg/kg/month. The main outcomes were achievement of disease remission and reduction of corticosteroid dose. Results The mean age ± standard deviation of patients was 69 ± 8 years. The main clinical features at TCZ onset were polymyalgia rheumatica ( n = 16), asthenia ( n = 7), headache ( n =5), constitutional symptoms ( n = 4), jaw claudication ( n = 2), and visual loss ( n = 2). Besides corticosteroids and before TCZ onset, 19 of 22 patients had also received several conventional immunosuppressive and/or biologic drugs. Of 22 patients, 19 achieved rapid and maintained clinical improvement following TCZ therapy. Also, after a median follow-up of 9 (interquartile range: 6–19) months, the C-reactive protein level had fallen from 1.9 (1.2–5.4) to 0.2 (0.1–0.9) mg/dL ( p < 0.0001) and the erythrocyte sedimentation rate decreased from 44 (20–81) to 12 (2–20) mm/1st hour ( p = 0.001). The median dose of prednisone was also tapered from 18.75 (10–45) to 5 (2.5–10) mg/day ( p < 0.0001). However, TCZ had to be discontinued in 3 patients due to severe neutropenia, recurrent pneumonia, and cytomegalovirus infection. Moreover, 1 patient died after the second infusion of TCZ due to a stroke in the setting of an infectious endocarditis. Conclusion TCZ therapy leads to rapid and maintained improvement in patients with refractory GCA and/or with unacceptable side effects related to corticosteroids. However, the risk of infection should be kept in mind when using this drug in patients with GCA. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether rheumatoid arthritis (RA) and psoriatic arthritis (PsA) can be differentiated in the early stages of the disease (duration of symptoms ≤1 year) on the basis of magnetic resonance imaging (MRI) features of the hand and wrist. Material and methods: Twenty early RA and 17 early PsA patients with symptomatic involvement of the wrist and hand joints and inconclusive radiographic studies were examined prospectively with contrast-enhanced MRI. Images were evaluated in accordance with the Outcome Measures in Rheumatology Clinical Trials recommendations. Results: Certain MRI features, such as the presence of enthesitis or extensive diaphyseal bone marrow edema, were observed exclusively in PsA (P = 0.0001). These distinctive findings were present in nearly 71% (12/17) of PsA patients. Diffuse and, in some cases, pronounced soft-tissue edema spreading to the subcutis was also seen more frequently in patients with PsA (P = 0.002). There were no significant differences in the frequency of synovitis, bone erosions, subchondral bone edema, or tenosynovitis between the 2 groups. However, in RA extensor tendons were involved more often than the flexor tendons, whereas in PsA the opposite was observed (P = 0.014). With respect to the discriminatory power of the different MRI findings examined, only the presence of enthesitis or diaphyseal bone edema and, to a lesser extent, the pattern of hand tendon involvement and the presence of soft-tissue edema accurately differentiated PsA from RA (all these features achieved accuracies greater than 0.70). Conclusions: We observed significant differences in the MRI findings of the hand and wrist that can help to distinguish between RA and PsA in the early stages of disease. This imaging method could help to assist in the differential diagnostic process in selected patients in whom diagnosis cannot be unequivocally established after conventional clinical, biochemical, and radiographic examinations. [Copyright &y& Elsevier]

Objective: To review and summarize the information available on the effectiveness and safety of biological therapies in refractory Felty''s syndrome (FS). Methods: We describe a case of FS with severe neutropenia and recurrent bacterial infections unresponsive to disease-modifying antirheumatic drug treatment and long-term administration with granulocyte colony-stimulating factor, in which treatment with rituximab (RTX) was useful and resulted in a sustained neutrophil response. Current evidence on the use of biological therapies in FS is also analyzed through a systematic review of the English-language literature, based on a PubMed search. Results: Available data on the use of biological therapies in refractory FS are based only on several case reports and are limited to the use of RTX and some anti-tumor necrosis factor α agents (etanercept, infliximab, and adalimumab). Including the case described here, data are available on 8 patients treated with RTX. A sustained increase in the absolute neutrophil count (>1500/mm3) was observed in 62.5% (5/8) of these patients after 1 cycle of treatment. In most of them, the hematological response was accompanied by a parallel improvement in biological markers of inflammation and other clinical manifestations of FS (arthritis, recurrent infections, systemic symptoms, etc). After a median follow-up of 9 months (range, 6-14), only 1 of these patients relapsed and neutropenia reappeared; in this patient, retreatment was rapidly effective. No significant adverse events related to RTX therapy were reported. Experience with anti-tumor necrosis factor agents is limited to 6 patients, none of whom presented any sustained increase in neutrophil count. Conclusions: Although it is not yet possible to make definite recommendations, the global analysis of all cases reported to date only supports the use of RTX as a second-line therapy in patients with refractory FS. [Copyright &y& Elsevier]

Objective: To compare the effectiveness and safety of a combination of rituximab (RTX) with either methotrexate (MTX) or leflunomide (LEF) in the treatment of patients with active rheumatoid arthritis (RA) and inadequate response to anti-tumor necrosis factor agents or traditional disease-modifying antirheumatic drugs (DMARD) in a real-world setting. Methods: Data from 77 consecutive unselected patients with active RA and treated with at least 1 cycle of RTX (1 g × 2 weeks) plus MTX or LEF were retrospectively collected. A comparative study between the 2 combinations of treatment (RTX+MTX and RTX+LEF) was performed at 6 months of follow-up considering 3 outcomes: the improvement of RA disease activity, the evolution of functional disability, and the tolerability and side effect profile. Results: Of the 77 patients, 45 received RTX+MTX and 32 RTX+LEF. At baseline there were no significant differences between the groups in terms of the main clinical and laboratory data, or in the number of previous DMARD and anti-tumor necrosis factor agents used. At 6 months of follow-up, we did not find significant differences between the 2 combinations in the evolution of RA disease activity (DAS28 response, according to the European League Against Rheumatism (EULAR) improvement criteria) and functional disability progression (health assessment questionnaire) over time. Minor adverse events occurred in 9% of RTX+MTX patients and in 9% of RTX+LEF patients. None of the patients had serious adverse events and none discontinued the treatment during the study period. Conclusions: Our preliminary data support the view that LEF is a useful alternative if MTX is contraindicated, since its effectiveness and safety seem similar. [Copyright &y& Elsevier]

Objective: To review and summarize published information on the effectiveness and safety of rituximab (RTX) in adult patients with refractory neuropsychiatric systemic lupus erythematosus (NPSLE). Methods: We describe a patient with persistently active NPSLE, despite conventional therapy, who responded dramatically to RTX. Current evidence on the therapeutic use of RTX in this complex situation is also analyzed through a systematic review of the English-language literature, based on a PubMed search. Results: Available data on the use of RTX in refractory NPSLE come from a large number of case reports and some open-label studies. Including our case, 35 patients have been well documented. A complete or partial therapeutic response was achieved in 85% of patients after 1 cycle of treatment. A positive correlation between serological markers of disease activity and clinical outcome has also been demonstrated in some of these patients. Clinical improvement was accompanied by a significant reduction in the daily dose of oral corticosteroids. Relapse after RTX treatment was noted in 45% of cases (median 9.5 months; range, 4-33 months). Infections were observed in 29% of patients. Conclusion: Evidence for the effectiveness of RTX as induction therapy in NPSLE is based solely on several case reports and noncontrolled trials. Although it is not yet possible to make definite recommendations, the global analysis of these cases supports the off-label use of RTX in cases of severe refractory NPSLE. [Copyright &y& Elsevier]

Objectives: The observed higher incidence of pyogenic vertebral osteomyelitis (PVO) may entail an increasing number of patients with no microbiologic diagnosis. The true incidence of these cases, how exhaustive the etiologic diagnostic efforts must be, and the usefulness of an empirical antibiotic therapy are not well defined. Methods: Retrospective analysis of all cases of vertebral osteomyelitis in our center (1991-2009) and retrospective analysis of cases of PVO (2005-2009). Clinical data, diagnostic procedures, treatment, and outcome were reviewed. A comparative analysis between microbiologically confirmed PVO (MCPVO) and probable PVO (PPVO) was performed. Results: Increasing incidence of PVO (+0.047 episodes/100,000 inhabitants-year). During the last decade, there was an increase of PPVO (+0.059 episodes/100,000 inhabitants-year) with stable incidence of MCPVO. During 2005-2009, there were 72 patients [47 (65%) MCPVO and 25 (35%) PPVO]. 60% men; mean age was 66 years. Bacteremia was found in 59%. Computed tomographic guided vertebral biopsy, positive in 7/36 (19%), was more successful among patients with bacteremia. Among MCPVO, there was an increasing proportion of less virulent bacteria. Cases of MCPVO presented more frequently with sepsis, fever, and high acute-phase reactants, and PPVO cases were mostly treated with oral fluoroquinolones plus rifampin. No differences were found between both groups in outcome (93% success, 22% sequelae). Conclusions: An epidemiologic change of PVO is suggested by a higher incidence of PPVO and the isolation of less virulent microorganisms among MCPVO. In this setting, the availability of an oral and effective empirical antibiotic therapy may challenge an exhaustive prosecution of the etiology. [Copyright &y& Elsevier]

Background and Objective: Lobular panniculitis, together with polyarthritis and intraosseous fat necrosis, may occasionally complicate pancreatic disease. This triad is known in the literature as the pancreatitis, panniculitis, and polyarthritis (PPP syndrome). We describe a case of the PPP syndrome and review the available literature to summarize the clinical characteristics of patients with this condition. Methods: A patient with the PPP syndrome, with evidence of extensive intraosseous fat necrosis in the joints involved revealed by magnetic resonance imaging, is described and the relevant literature based on a PubMed search from 1970 to February 2008 is reviewed. The keywords used were pancreatitis or pancreatic disease, panniculitis, arthritis, and intraosseous fat necrosis. Results: Including our case, 25 well-documented patients with the PPP syndrome have been reported. Our patient had few abdominal symptoms despite high serum levels of pancreatic enzymes. In our review of the literature, almost 2/3 of patients had absent or mild abdominal symptoms, leading to misdiagnosis. The delay in diagnosis and specific treatment of the underlying pancreatitis worsens the prognosis of this condition, which has a mortality rate as high as 24%. In nearly 45% of the patients, the arthritis follows a chronic course with a poor response to nonsteroidal anti-inflammatory drugs and corticosteroids, and the rapid development of radiographic joint damage. Conclusion: Certain forms of pancreatic disease can very occasionally cause arthritis and panniculitis. Although uncommon, physicians should be alert to the possible presence of this syndrome for 2 reasons: first, unrecognized pancreatic disease can be fatal if not treated promptly; second, to avoid inappropriate and risky therapy to improve joint symptoms. [Copyright &y& Elsevier]

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Factors associated with chronic heart failure (CHF) in patients with systemic lupus erythematosus (SLE) have received little attention. Recent data on the use of hydroxychloroquine in the treatment of SARS-CoV-2 infection have cast doubt on its cardiac safety. The factors associated with CHF, including therapy with antimalarials, were analyzed in a large multicenter SLE cohort. Cross-sectional study including all patients with SLE (ACR-1997 criteria) included in the Spanish Society of Rheumatology Lupus Register (RELESSER), based on historically gathered data. Patients with CHF prior to diagnosis of SLE were excluded. A multivariable analysis exploring factors associated with CHF was conducted. The study population comprised 117 patients with SLE (ACR-97 criteria) and CHF and 3,506 SLE controls. Ninety percent were women. Patients with CHF were older and presented greater SLE severity, organ damage, and mortality than those without CHF. The multivariable model revealed the factors associated with CHF to be ischemic heart disease (7.96 [4.01–15.48], p < 0.0001), cardiac arrhythmia (7.38 [4.00–13.42], p < 0.0001), pulmonary hypertension (3.71 [1.84–7.25], p < 0.0002), valvulopathy (6.33 [3.41–11.62], p < 0.0001), non-cardiovascular damage (1.29 [1.16–1.44], p < 0.000) and calcium/vitamin D treatment (5.29 [2.07–16.86], p = 0.0015). Female sex (0.46 [0.25–0.88], p = 0.0147) and antimalarials (0.28 [0.17–0.45], p < 0.000) proved to be protective factors. Patients with SLE and CHF experience more severe SLE. Treatment with antimalarials appears to confer a cardioprotective effect. [ABSTRACT FROM AUTHOR]

Objective: To investigate the frequency and clinical significance of bone marrow edema (BME) in a series of patients with rheumatoid arthritis (RA) and symptomatic involvement of the cervical spine. Methods: We studied 19 consecutive RA patients with cervical spine magnetic resonance imaging (MRI) according to a specifically designed protocol that included short inversion time inversion recovery sequences. All cases had neck pain unresponsive to conventional treatment, neurological symptoms, or signs suggestive of cervical myelopathy, or cervical pain with evidence of atlantoaxial subluxation on radiographs. Results: The mean age of the 19 patients (15 women and 4 men) at time of the study was 59 ± 12 years (range, 23-82) and the median disease duration was 14 ± 7.4 years (range, 4-30). BME was observed in 74% (14/19) of the patients: at the atlantoaxial level alone in 16% of the patients; subaxially alone in 16%; and at both levels in 42% of the patients. At the atlantoaxial level, BME was usually observed involving the odontoid process, whereas subaxially BME was limited to the vertebral plates and the interapophyseal joints. Patients with BME had higher erythrocyte sedimentation rate (ESR) values at the time of MRI examination (P = 0.014) and more severe atlantoaxial joint MRI synovitis scores (P = 0.05) compared with the remaining patients; the frequency of odontoid erosions was also greater in this group, but the difference did not reach statistical significance. Altogether, these data suggest a more severe inflammatory response in these patients. In this group a significant correlation was found between BME scores at atlantoaxial level and (1) ESR values (r = 0.854; P = 0.001) and (2) atlantoaxial joint MRI synovitis scores (r = 0.691; P = 0.001). Conclusion: BME is frequently observed in patients with established RA and symptomatic cervical spine involvement. Both atlantoaxial and subaxial levels are equally affected. The presence of BME seems related to the intensity of the inflammatory response and to the severity of the atlantoaxial joint synovitis. [Copyright &y& Elsevier]

Objective: The diagnosis of rheumatoid arthritis (RA) is sometimes difficult to establish early in the disease process, particularly in the absence of its classic hallmarks. Our aim was to compare the practical usefulness of magnetic resonance imaging (MRI) of the hand versus anticyclic citrullinated peptide (anti-CCP) antibody testing to confirm the diagnosis of clinically suspected RA in the absence of rheumatoid factor (RF) and radiographic erosions. Methods: We prospectively included patients with early inflammatory arthritis and strong clinical suspicion of RA, in whom initial complementary tests (RF and radiographs of hands, wrists, and feet) did not provide unequivocal confirmation of the diagnosis. In all patients, anti-CCP antibodies were assessed and contrast-enhanced MRI of the most affected hand was performed according to a specifically designed protocol. The MRI criterion for the diagnosis of RA was either the presence of synovitis with bone erosions or bone marrow edema, which is currently considered to be a forerunner of erosions. Results: In the 40 patients (28 women), the mean age at diagnosis was 54 ± 6 years and the median duration of symptoms was 4 ± 2.6 months (range 1.5 to 12). Final diagnoses at 1-year follow-up were RA in 31 patients, undifferentiated arthritis in 7 (5 self-limiting), and psoriatic arthropathy (PsA) and antisynthetase syndrome in 1 patient each. Anti-CCP antibodies were positive only in 7 patients, all of whom were finally diagnosed with RA. The prevalence of anti-CCP positivity in our series of seronegative RA patients was thus 23% (7/31); in these patients the anti-CCP antibodies had a specificity of 100% (95% CI: 71.7 to 100) and sensitivity of 23% (95% CI: 9.6 to 41.1). Use of the MRI criterion led to the correct diagnosis in 100% of patients with RA and to false-positive results (1 with PsA and 1 with antisynthetase syndrome). The MRI criterion had a specificity of 78% (95% CI: 40.0 to 97.2) and sensitivity of 100% (95% CI: 90.8 to 100) for identification of seronegative RA. Conclusion: Although the tests are not mutually exclusive, in our experience MRI is more helpful than anti-CCP antibody determination in confirming the diagnosis of clinically suspected early RA in patients in whom the diagnosis cannot be confirmed using conventional methods. [Copyright &y& Elsevier]

Objectives: Management of abscess-associated spontaneous pyogenic vertebral osteomyelitis (PVO) is controversial. The role of magnetic resonance imaging (MRI) in follow-up and its relation with clinical outcome is often unclear. This study evaluates the clinical and MRI outcome of abscess-associated PVO under conservative treatment. Methods: Prospective study and retrospective review of patients with spontaneous PVO in whom the initial MRI showed soft-tissue involvement (STI). Treatment according to a medical protocol, clinical and MRI follow-up at diagnosis, and at 2 later time points: early response (ER, at the end of antibiotic therapy) and late response (LR, ≥6 months after therapy). MRI classified STI as soft-tissue edema (STE) or abscess. Results: Of the 27 patients (20 men, 74%, age 65 ± 14), all had pain, 17 (63%) had fever, and 6 (22%) had mild neurological impairment. The main etiology was Staphylococcus sp (11, 41%). Twenty-one (81%) had bacteremia and 18 (67%) had epidural/paraspinal abscess. Patients received antibiotics for 9 weeks, administered orally for 6 weeks. ER: Three cases failed and general improvement was seen in the remainder. MRI showed persistent STI, which diminished in all cases except 1, whereas bone/disc findings remained. LR: All patients were cured; 8 reported mild sequelae (30%). MRI still revealed bone/disc abnormalities, but residual STE was infrequent. Median follow-up was 29 months. Conclusion: Most patients with abscess-associated spontaneous PVO are cured with a conservative approach. MRI shows STI reduction at ER evaluation. Repeat MRI is probably unnecessary if clinical and laboratory outcomes are satisfactory. The persistence of bone/disc MRI findings alone does not represent therapeutic failure. [Copyright &y& Elsevier]

Objective: To determine the impact of prior corticosteroid treatment on temporal artery biopsy (TAB) yield to establish the diagnosis of giant cell arteritis (GCA). Methods: Retrospective study of a consecutive cohort of 78 patients clinically diagnosed and managed as GCA, who received corticosteroids before TAB. Results: Among the 78 patients, TAB was positive in 57 (73%) and negative in 21 (27%). No significant differences in the length of the specimen were found between the positive and negative biopsies. We grouped patients according to treatment duration before TAB. In those with newly diagnosed GCA treated with high-dose steroid therapy, the biopsy results were positive in 78% (35/45) of patients treated for less than 2 weeks, in 65% of those treated for 2 to 4 weeks (13/20), and in 40% of those treated for more than 4 weeks (2/5). We also observed 8 patients that developed GCA on a background of a prior history of polymyalgia rheumatica (PMR); in this group biopsy was positive in 88% of the cases, after a median duration of treatment of 180 ± 172 days and an average daily dose of 7.1 ± 1.4 mg/d. Conclusion: The performance of TAB should not delay the prompt institution of steroid therapy on diagnosis of GCA, since the diagnostic yield of TAB seems valuable within 4 weeks of starting high-dose steroid treatment. In patients that developed GCA on a background of a prior history of PMR, a late TAB is also generally informative despite long-term treatment with low doses of corticosteroids. [Copyright &y& Elsevier]

Objective: Since statins interfere with a variety of immune-inflammatory pathways shared by atherosclerosis and giant cell arteritis (GCA), they might be potentially useful as adjunctive therapy to glucocorticosteroids in GCA. Our aim was to examine whether concomitant use of statins had any potential benefit in GCA. Methods: Retrospective follow-up study of an unselected population of 121 patients with GCA. A comparative analysis between patients with and without statin therapy was performed. Results: At the time of the GCA diagnosis, 30 patients (25%) had already been receiving statins and continued taking them during the corticosteroid treatment. No statistically significant reduction in the incidence of severe ischemic complications (including visual manifestations, jaw claudication, cerebrovascular accidents, ischemic heart disease, and limb claudication due to large artery stenosis) was observed in this group compared with the remaining patients. When we analyzed follow-up data, we found no significant differences between groups in terms of frequency of relapses, incidence of aortitis, and percentage of patients recovered from GCA. The duration of therapy and corticosteroids requirements among patients in permanent remission was similar in both groups. Conclusion: We did not observe a significant benefit derived from the use of statins at low to moderate doses in the incidence of severe ischemia or the disease outcome. [Copyright &y& Elsevier]

Objective: To analyze the clinical features, approaches to management, and outcome of spontaneous pyogenic facet joint infection (PFJI) in adults. Patients and methods: Case series of 10 adults with microbiologically proven PFJI diagnosed during a 10-year period in a teaching hospital, plus a review of 32 additional cases previously reported (PubMed 1972 to 2003). Patients with prior spinal instrumentation or surgery and injection drug users were excluded. Only cases that were sufficiently detailed to be individually analyzed were included. These 32 cases, together with our 10 patients, form the basis of the present analysis. Results: PFJI represented nearly 20% of all spontaneous pyogenic spinal infection diagnosed in our hospital during a 10-year period. This data suggest that PFJI is more common than was previously thought. Of the 42 patients with PFJI, 26 (62%) were men and 16 (38%) were women, with ages ranging from 20 to 86 years (mean age, 59 ± 15 years); 55% of patients were older than 60 years. The most common location of infections was the lumbosacral region (86%). All patients presented with severe back pain; fever was noted in 83% of the cases and neurological impairment in nearly 48%. In 38% of patients a systemic predisposing factor for infection was present; the most common conditions were diabetes mellitus, malignancies, and alcoholism. In almost 36% of cases, one or more concomitant infectious processes due to the same microorganism was found, mainly arthritis, skin and soft-tissue infections, endocarditis, and urinary tract infections. Staphylococcus aureus was the most common etiologic microorganism (86% of cases). Bacteremia was documented in 81% of the cases. The diagnosis of PFJI was based mainly on imaging study findings. Paraspinal and/or epidural extension was frequent (81% of cases), but its presence did not indicate a worse prognosis. Medical treatment alone was usually successful. The overall prognosis of PFJI was good, with a mortality rate of only 2%. The great majority of patients were cured without functional sequelae. Conclusion: Incidence data from our institution reveal that PFJI is not a rare condition, representing approximately 20% of all pyogenic spinal infections. This entity should be considered in the differential diagnosis of patients with low back pain, especially in the presence of fever, whatever the patient’s immunological status. [Copyright &y& Elsevier]