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Background: Overactivation of the interferon pathways has been demonstrated in patients suffering from different systemic autoimmune diseases (SADs). Genetic associations have been described for many genes involved in these pathways. Gain-of-function mutations in theTMEM173gene have recently been reported in patients with autoinflammatory diseases that share some clinical features with SADs.Methods: We aimed at detecting the reported three mutations of transmembrane protein 173 (TMEM173) exon 5 in 100 patients suffering from: systemic lupus erythematosus (SLE) (n = 22), primary antiphospholipid syndrome (PAPS) (n = 20), systemic sclerosis (SSc) (n = 20), dermatomyositis (DM) (n = 20), and vasculitis (n = 18). Samples from 19 healthy controls were also included. Sequence analyses were performed from the derivedTMEM173exon 5 PCR fragment amplified from DNA obtained from whole blood.Results: Neither mutations nor single nucleotide polymorphisms (SNPs) in the exon 5 of theTMEM173gene were detected. Just the rs7380272 SNP, located in the intronic region upstream exon 5, was detected in some patients and controls. The allele frequency of this SNP, though, was not statistically different between the patients groups and the control group.Conclusions: Our study demonstrates the lack of association between the presence of SADs and mutations in exon 5 of theTMEM173gene. SADs are complex multifactorial diseases in which not just one but probably many different genetic alterations may coexist. Although we cannot rule out the possibility that other variations may exist in other regions of this gene, we think that studies must be directed towards the analysis of other genes which, asTMEM173, also code for nucleic acid sensors that activate the nucleic-acid induced type I IFN pathway. [ABSTRACT FROM AUTHOR]

Our objective was to determine the prevalence of antinuclear antibodies (ANAs) in patients with malignancies and to investigate if their presence might be related with development of musculoskeletal symptoms or paraneoplastic rheumatic syndromes. Antinuclear antibodies were determined by indirect immunofluorescence on Hep-2 cells in 274 neoplastic patients and in a control group of 140 age-adjusted healthy subjects. Antinuclear antibody specificities (anti-DNA and antiENA) were investigated in patients with rheumatological symptoms and positive ANA. Antinuclear antibodies were detected in 76 of 274 (27.7%) patients with malignancies and in nine of 140 (6.4%) healthy subjects. Twenty patients reported paraneoplastic rheumatic symptoms or syndromes. Two of them developed clinical symptoms mimicking rheumatoid arthritis (rheumatoid-like arthropathy), one systemic lupus erythematosus (lupus-like syndrome), one dermatomyositis and four cutaneous vasculitides. Musculoskeletal symptoms and paraneoplastic rheumatic symptoms and syndromes were both more frequently observed in patients with positive ANA. Antinuclear antibody specificities were found in only two cases. We can conclude that there is an increased incidence of antinuclear antibodies in malignant conditions. Musculoskeletal symptoms and rheumatic paraneoplastic symptoms and syndromes seem to be more frequent in patients with cancer-related positive ANAs. The failure to find ANA specificities (anti-ENA, anti-DNA) in patients with malignancies and positive ANAs in our study may simply reflect molecular differences between the autoantigens involved in cancer and those characteristically involved in the systemic autoimmune diseases. [ABSTRACT FROM AUTHOR]

Background: Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) are rare autoimmune diseases characterized by inflammation of blood vessels. This study aimed to assess the cost-utility of avacopan in combination with rituximab (RTX) or cyclophosphamide (CYC) compared with glucocorticoids (GC) for the treatment of severe, active AAV in Spain., Methods: A 9-state Markov model was designed to reflect the induction of remission and sustained remission of AAV over a lifetime horizon. Clinical data and utility values were mainly obtained from the ADVOCATE trial, and costs (€ 2022) were sourced from national databases. Quality-adjusted life years (QALYs), and incremental cost-utility ratio (ICUR) were evaluated. An annual discount rate of 3% was applied. Sensitivity analyses were performed to examine the robustness of the results., Results: Avacopan yielded an increase in effectiveness (6.52 vs. 6.17 QALYs) and costs (€16,009) compared to GC, resulting in an ICUR of €45,638 per additional QALY gained. Avacopan was associated with a lower incidence of end-stage renal disease (ESRD), relapse and hospitalization-related adverse events. Sensitivity analyses suggested that the model outputs were robust and that the progression to ESRD was a driver of ICUR., Conclusions: Avacopan is a cost-effective option for patients with severe, active AAV compared to GC in Spain.

Eosinophil-related diseases represent a group of pathologic conditions with highly heterogeneous clinical presentation and symptoms ranging from mild to critical. Both systemic and localized forms of disease are typically treated with glucocorticoids. The approval of novel biologic therapies targeting the interleukin-5 pathway can help reduce the use of systemic glucocorticoids (SGC) in eosinophilic diseases and reduce the risk of SGC-related adverse effects (AEs). In this article, a panel of experts from different medical specialties reviewed current evidence on the use of SGC in two systemic eosinophilic diseases: Eosinophilic Granulomatosis with PolyAngiitis (EGPA) and HyperEosinophilic Syndrome (HES); and in two single-organ (respiratory) eosinophilic diseases: Chronic RhinoSinusitis with Nasal Polyps (CRSwNP) and Severe Asthma with Eosinophil Phenotype (SA-EP), and contrasted it with their experience in clinical practice. Using nominal group technique, they reached consensus on key aspects related to the dose and tapering of SGC as well as on the initiation of biologics as SGC-sparing agents. Early treatment with biologics could help prevent AEs associated with medium and long-term use of SGC., Competing Interests: VP has received consulting, speaker fees, grants and support to attend international congresses from AstraZeneca, GSK and Sanofi. IB has received fees from GSK, Novartis, Sanofi, AstraZeneca and Teva for talks at scientific events and as member of advisory boards. MJR has received lecture fees from Novartis, GSK, LETI, Astra-Zéneca, Chiesi and TEVA. GE-F has received consulting fees from GSK and Janssen and support to attend congress from Boehringer Ingelheim. RSL has received consulting fees from GSK and support to attend congresses from Menarini. JMH-R has received honoraria from Amgen, Novartis, Celgene/BMS, Pfizer and GSK and is a member of Novartis, Pfizer, Amgen and Celgene/BMS advisory boards. He has received consulting fees from GSK and research support from Novartis and Celgene/BMS. EM has received consulting fees from GSK. AC-L has received fees in the last 3 years for talks at meetings sponsored by AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, Ferrer, GlaxoSmithKline, MSD, Novartis, Orion Pharma, and Sanofi; travel and attendance expenses for conferences from Bial, Gebro, GlaxoSmithKline, Novartis, and TEVA; and funds/grants for research projects from several state agencies, non-profit foundations, and AstraZeneca and GlaxoSmithKline. JLIA has received fees for consultancy, projects, and talks from AstraZeneca, Bayer, Boehringer Ingelheim, Chiesi, Glaxo, Grifols, Smith Kline, Menarini, Novartis, Orion, Pfizer, Sandoz, and Teva. MSDS has received fees from GSK, Sanofi, MSD and MEDA for talks at scientific events and is a member of advisory boards. JM-S has received fees from GSK, Sanofi, AstraZeneca and Teva for talks at scientific events and as member of advisory boards. BA-M has received grants and research support from Abbvie and Roche, and fees for consulting or participating in company-sponsored speakers bureaus from GSK, Boehringer Ingelheim and Janssen. DB-C and ALM are employees of GSK and hold stocks/shares in GSK. ÍR-F: has received consulting fees from GSK and is on GSK’s advisory board for mepolizumab., (Copyright © 2024 del Pozo, Bobolea, Rial, Espigol-Frigolé, Solans Laqué, Hernández-Rivas, Mora, Crespo-Lessmann, Izquierdo Alonso, Domínguez Sosa, Maza-Solano, Atienza-Mateo, Bañas-Conejero, Moure and Rúa-Figueroa.)

Background: Two clinical subsets of giant cell arteritis have been identified with different histological and CT findings. However, PET/CT findings have not been compared with temporal artery biopsy (TAB)., Objective: The aims of this study were to describe clinical and histological findings in patients with giant cell arteritis according to the presence or absence of aortitis in PET/CT at the disease diagnosis, and to identify independent factors related to aortic involvement., Methods: Patients were included and followed prospectively. Clinical symptoms and TAB findings were recorded. PET/CT was performed in the first 10 days of steroid therapy. Aortitis was defined if a grade 3 uptake on visual analysis was present on arterial wall. Clinical and histological variables were compared according to the presence or absence of aortitis on PET/CT. Multivariate analysis was performed to identify independent factors related to the presence of aortitis., Results: Twenty-seven patients (median age, 77.6 years) were included. PET/CT was performed with a median delay of 5.0 days. Aortitis was observed in 8 patients. Patients with aortitis were younger (69.9 vs 83.7 years, P = 0.04) and had less frequently ischemic manifestations (25.0% vs 84.2%, P = 0.006) than patients without aortitis. Giant multinucleated cells were more frequent on TAB from patients with aortitis (71.4% vs 16.7%), and its presence was an independent risk factor for the occurrence of aortic involvement on PET/CT (odds ratio, 12.2; P = 0.046)., Conclusions: Our study shows that giant cells on TAB are associated with the presence of aortitis on PET/CT. Patients with aortic involvement are younger and show less frequently ischemic manifestations., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To assess the efficacy and safety of tocilizumab (TCZ) in Caucasian patients with refractory Takayasu's arteritis (TAK) in clinical practice., Methods: A multicenter study of Caucasian patients with refractory TAK who received TCZ. The outcome variables were remission, glucocorticoid-sparing effect, improvement in imaging techniques, and adverse events. A comparative study between patients who received TCZ as monotherapy (TCZ MONO ) and combined with conventional disease modifying anti-rheumatic drugs (cDMARDs) (TCZ COMBO ) was performed., Results: The study comprised 54 patients (46 women/8 men) with a median [interquartile range (IQR)] age of 42.0 (32.5-50.5) years. TCZ was started after a median (IQR) of 12.0 (3.0-31.5) months since TAK diagnosis. Remission was achieved in 12/54 (22.2%), 19/49 (38.8%), 23/44 (52.3%), and 27/36 (75%) patients at 1, 3, 6, and 12 months, respectively. The prednisone dose was reduced from 30.0 mg/day (12.5-50.0) to 5.0 (0.0-5.6) mg/day at 12 months. An improvement in imaging findings was reported in 28 (73.7%) patients after a median (IQR) of 9.0 (6.0-14.0) months. Twenty-three (42.6%) patients were on TCZ MONO and 31 (57.4%) on TCZ COMBO : MTX ( n  = 28), cyclosporine A ( n  = 2), azathioprine ( n  = 1). Patients on TCZ COMBO were younger [38.0 (27.0-46.0) versus 45.0 (38.0-57.0)] years; difference (diff) [95% confidence interval (CI) = -7.0 (-17.9, -0.56] with a trend to longer TAK duration [21.0 (6.0-38.0) versus 6.0 (1.0-23.0)] months; diff 95% CI = 15 (-8.9, 35.5), and higher c-reactive protein [2.4 (0.7-5.6) versus 1.3 (0.3-3.3)] mg/dl; diff 95% CI = 1.1 (-0.26, 2.99). Despite these differences, similar outcomes were observed in both groups (log rank p  = 0.862). Relevant adverse events were reported in six (11.1%) patients, but only three developed severe events that required TCZ withdrawal., Conclusion: TCZ in monotherapy, or combined with cDMARDs, is effective and safe in patients with refractory TAK of Caucasian origin., Competing Interests: Conflict of interest statement: Disclosures that might be interpreted as constituting of possible conflict(s) of interest for the study: DP-P is supported by a research contract from the Carlos III Health Institute of Spain (Rio Hortega program, ref. CM20/00006) and has received research support from UCB Pharma, Roche, Sanofi, Pfizer, AbbVie, and Lilly. MAG-G received grants/research supports from Abbvie, MSD, Jansen, and Roche and had consultation fees/participation in company sponsored speaker’s bureau from Abbvie, Pfizer, Roche, Sanofi, Lilly, Celgene, and MSD. RB received grants/research supports from Abbvie, MSD, and Roche, and had consultation fees/participation in company sponsored speaker’s bureau from Abbvie, Lilly, Pfizer, Roche, Bristol-Myers, Janssen, UCB Pharma, and MSD. The remaining authors declare they do not have conflict of interest., (© The Author(s), 2021.)

Objectives: A potential point of concern among clinicians is whether results derived from the clinical trials can be reasonably applied or generalised to a definable group of patients seen in real world. It can be the case of the GiACTA study that is a phase III randomised controlled trial of tocilizumab (TCZ) in giant cell arteritis (GCA). To address this question, we compared the clinical features and the responses to TCZ from the GiACTA trial patients with those from a series of GCA seen in the daily clinical practice., Methods: Comparative study of clinical features between patients from the GiACTA trial (overall n=251) and those from a multicentre series of real-world GCA patients undergoing TCZ therapy (n=134). The diagnosis of GCA in the GiACTA trial was established by the ACR modified criteria whereas in the series of real-world patients it was made by using the ACR criteria, a positive biopsy of temporal artery or the presence of imaging techniques consistent with large-vessel vasculitis in individuals who presented cranial symptoms of GCA. GiACTA trial patients received subcutaneous TCZ (162 mg every 1 or 2 weeks) whereas those from the clinical practice series were treated using standard IV dose (8 mg/kg/month) or subcutaneous (162 mg/week)., Results: Real-life patients undergoing TCZ were older with longer disease duration and higher values of ESR and had received conventional immunosuppressive therapy (mainly methotrexate) more commonly than those included in the GiACTA trial. Despite clinical differences, TCZ was equally effective in both GiACTA trial and clinical practice patients. However, serious infections were more commonly observed in GCA patients recruited from the clinical practice., Conclusions: Despite clinical differences with patients recruited in clinical trials, data from real-life patients confirm the efficacy of TCZ in GCA.

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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: To define disease activity levels, minimal clinically important improvement (MCII) and patient-acceptable symptom state (PASS) with the primary Sjögren's syndrome (SS) disease activity indexes: European League Against Rheumatism (EULAR) SS disease activity index (ESSDAI) and EULAR SS patient-reported index (ESSPRI)., Methods: For 790 patients from two large prospective cohorts, ESSDAI, physician evaluation of disease activity, ESSPRI and patients' satisfaction with their current health status were recorded. Receiver operating characteristic curve analyses and anchoring methods were used to estimate disease activity levels of ESSDAI and the PASS of ESSPRI. At follow-up visit, patients and physicians assessed, respectively, whether symptoms and disease activity have improved or not. An anchoring method based on this evaluation was used to estimate MCII of ESSDAI and ESSPRI., Results: Low-activity (ESSDAI<5), moderate-activity (5≤ESSDAI≤13) and high-activity (ESSDAI≥14) levels were defined. MCII of ESSDAI was defined as an improvement of at least three points. The PASS estimate was defined as an ESSPRI<5 points and MCII as a decrease of at least one point or 15%., Conclusions: This study determined disease activity levels, PASS and MCII of ESSDAI and ESSPRI. These results will help designing future clinical trials in SS. For evaluating systemic complications, the proposal is to include patients with moderate activity (ESSDAI≥5) and define response to treatment as an improvement of ESSDAI at least three points. For addressing patient-reported outcomes, inclusion of patients with unsatisfactory symptom state (ESSPRI≥5) and defining response as an improvement of ESSPRI at least one point or 15% seems reasonable., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

IgG4-related disease (IgG4-RD) is a rare entity consisting of inflammation and fibrosis that has been described in multiple organs. Concrete diagnostic criteria have been established recently and there is a lack of large series of patients.To describe the clinical presentation, histopathological characteristics, treatment and evolution of a series of IgG4-RD Spanish patients.A retrospective multicenter study was performed. Twelve hospitals across Spain included patients meeting the current 2012 consensus criteria on IgG4-RD diagnosis.Fifty-five patients were included in the study, 38 of whom (69.1%) were male. Median age at diagnosis was 53 years. Thirty (54.5%) patients were included in the Histologically Highly Suggestive IgG4-RD group and 25 (45.5%) in the probable IgG4-RD group. Twenty-six (47.3%) patients had more than 1 organ affected at presentation. The most frequently affected organs were: retroperitoneum, orbital pseudotumor, pancreas, salivary and lachrymal glands, and maxillary sinuses.Corticosteroids were the mainstay of treatment (46 patients, 83.6%). Eighteen patients (32.7%) required additional immunosuppressive agents. Twenty-four (43.6%) patients achieved a complete response and 26 (43.7%) presented a partial response (<50% of regression) after 22 months of follow-up. No deaths were attributed directly to IgG4-RD and malignancy was infrequent.This is the largest IgG4-RD series reported in Europe. Patients were middle-aged males, with histologically probable IgG4-RD. The systemic form of the disease was frequent, involving mainly sites of the head and abdomen. Corticosteroids were an effective first line treatment, sometimes combined with immunosuppressive agents. Neither fatalities nor malignancies were attributed to IgG4-RD.

Objectives: To validate the two recently developed disease activity indexes for assessment of primary Sjögren's syndrome (SS): the European League Against Rheumatism (EULAR) SS Patient Reported Index (ESSPRI) and the EULAR SS Disease Activity Index (ESSDAI)., Methods: A prospective international 6-month duration validation study was conducted in 15 countries. At each visit, physicians completed ESSDAI, SS disease activity index (SSDAI), Sjögren's Systemic Clinical Activity Index (SCAI) and physician global assessment (PhGA); and patients completed ESSPRI, Sicca Symptoms Inventory (SSI), Profile of Fatigue and Discomfort (PROFAD) and patient global assessment (PGA). Psychometric properties (construct validity, responsiveness and reliability) were evaluated and compared between scores., Results: Of the 395 patients included, 145 (37%) and 251 (64%) had currently active or current or past systemic manifestations, respectively. EULAR scores had higher correlation with the gold standard than other scores (ESSDAI with PhGA: r=0.59; ESSRPI with PGA: r=0.70). Correlations between patient and systemic scores were very low (ranging from 0.07 to 0.29). All systemic scores had similar large responsiveness in improved patients. Responsiveness of patient scores was low but was significantly higher for ESSPRI compared with SSI and PROFAD. Reliability was very good for all scores., Conclusions: ESSDAI and ESSPRI had good construct validity. All scores were reliable. Systemic scores had a large sensitivity to change in patients whose disease activity improves. Patient scores had a small sensitivity to change, however, significantly better for ESSPRI. Systemic and patient scores poorly correlated, suggesting that they are 2 complementary components that should be both evaluated, but separately., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objectives: To describe the clinical features of a large cohort of 496 Spanish patients with Behçet's disease (BD) and to analyse if patient's sex influenced the initial and cumulated prevalence of disease manifestations., Methods: Retrospective and descriptive study of 496 patients recruited in sixteen centres on the frame of the Spanish Registry of Behçet Disease Project Group. Demographic and clinical data are presented in addition to treatments and their related adverse effects. Clinical features at disease onset and during follow-up were compared according to the sex of the patients., Results: On the whole series, female to male ratio was 1.2:1.0. Mean age at disease onset was 28.7±12.6 years (range 17-73). Oral ulcers were the most frequent initial manifestation presented in 52.0% of patients. During follow-up, eye inflammatory disease was recorded in 45.1% of patients; thrombosis in 19.7% and central nervous system involvement in 13.5%. Men had higher prevalence of ocular involvement and venous thrombosis (52.5% vs. 39.2%, p=0.004 and 26.3% vs. 9.6%, p<0.001, respectively)., Conclusions: Spanish patients with BD presented similar clinical characteristics as their counterpart in the same geographical area and other world regions. In addition, we confirmed that ocular and vascular involvements are more frequent in men than in women.

Cutaneous complications associated with decorative tattooing are well known. However, the inhibition of a purpuric reaction by a tattoo is a fact that, as far as the authors know, has not been described before, fitting the definition of a 'sparing phenomenon', the absence of manifesting a particular skin disease in an area previously affected by another condition. From the clinical observation of purpuric lesions apparently inhibited by a tattoo in a 26-year-old patient, we performed an exact binomial test on the observed and expected proportion of purpuric lesions inside (0%, 95% confidence interval, CI, 0-2.6%) and outside (100%, 95% CI 97.4-100%) the tattooed skin, demonstrating a nonrandom distribution respecting the tattooed area (p < 0.001) and identifying the composition of the ink used in the tattoo (color pigment, glycerine, Hamamelis virginiana extract, water and alcohol). Moreover, we reviewed the cases of sparing phenomenon described in the literature. In conclusion this is the first report of a sparing phenomenon of purpuric lesions over tattooed skin., (© 2013 S. Karger AG, Basel.)

The Churg-Strauss Syndrome is an ANCA-associated vasculitis, an inflammatory multisystem disease with preference to the respiratory tract. Peripheral and tissue eosinophilia are the pathological hallmarks of this condition. The etiopathogenesis is unknown but some cytokines appear to play a central role and could be targets for new therapies., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Amyloidosis is a clinical disorder caused by extracellular deposition of proteins that are normally soluble as insoluble fibrils that damage different organs. More than 20 proteins can form amyloid deposits. All types of amyloid fibrils have a secondary structure with a β folded shape that is characteristic and makes them to adopt a green birefringence after stained with Congo red and viewed under cross-polarized light. Amyloidosis can be acquired or hereditary, systemic or localized, and are classified by the fibril precursor protein. Advances in the knowledge of the pathogenesis of amyloidosis allows the development of new diagnostic and therapeutical schemes that are currently under investigation., (Copyright © 2011 Elsevier España, S.L. All rights reserved.)

Objective: To assess the risk and predictors of lymphoma development in a large cohort of patients with primary Sjögren's syndrome (pSS)., Methods: Cox-regression analyses were used to study the predictive value of clinical and laboratory findings at pSS diagnosis, and Kaplan-Meier survival curves to compare survival probability between patients who developed lymphoma and the total cohort. Expected risk for lymphoma was calculated by comparison with the background population., Results: Eleven (4.5%) from 244 patients developed a non-Hodgkin lymphoma (NHL). Diffuse large B-cell and mucosa-associated lymphoid tissue lymphomas occurred at a similar frequency. Three (27.3%) patients died: 2 due to transformation from mucosa-associated lymphoid tissue to diffuse large B-cell. Purpura (HR 8.04, 95% confidence interval [CI] 2.33-27.67), parotidomegaly (HR 6.75, 95%CI 1.89-23.99), anemia (HR 3.43, 95%CI 1.04-11.35), leukopenia (HR 8.70, 95%CI 2.38-31.82), lymphocytopenia (HR 16.47, 95%CI 3.45-78.67), hypergammaglobulinemia (HR 4.06, 95%CI 1.06-15.58), low C3 (HR 36.65, 95%CI 10.65-126.18), and low C4 (HR 39.70, 95%CI 8.85-126.18) levels at pSS diagnosis were significant predictors of NHL development, but only hypocomplementemia and lymphocytopenia were independent risk factors. Hypocomplementemia was related to earlier development of NHL and higher mortality. The cumulative risk of developing lymphoma ranged from 3.4% in the first 5 years to 9.8% at 15 years. Standardized incidence ratio (95%CI) for NHL development was 15.6 (95%CI 8.7-28.2)., Conclusions: Patients with pSS have a 16-fold increased risk of developing lymphoma. This risk increases with time. Hypocomplementemia and lymphocytopenia at pSS diagnosis are the strongest predictors. Survival is clearly reduced in patients with hypocomplementemia. Indolent lymphomas tend to evolve over time toward a more aggressive histologic type., (Copyright © 2011 Elsevier Inc. All rights reserved.)

This study aims to determine the effectiveness of mycophenolate sodium (MS) in patients with scleroderma (SSc)-related interstitial lung disease (ILD). In a prospective observational study, we evaluated 14 consecutive SSc-ILD patients who were treated with MS for 12 months. The effect of MS on lung function was examined by using longitudinal data analytic methods. Wilcoxon rank-sum tests were used to examine the forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and diffusing capacity of the lung for carbon monoxide (DLCO) by pulmonary function testing. As a group, the median values for FVC, FEV1 and DLCO did not change significantly after 12 months of MS therapy and fulfilled the definition of stable disease by the American Thoracic Society. Individually, after 12 months of treatment, 6 out of 14 patients showed a pulmonary improvement defined as an increase of more than 10% in FVC, and 5 out of 14 patients remained stable. By contrast, the median FVC had declined a non-significant 7.2% from the previous 12 months before MS initiation. No significant drug adverse effects were registered. These prospective data suggest that MS is a safe and well-tolerated therapy for SSc-ILD patients, and it is capable of preventing functional pulmonary deterioration.

Objective: To analyse the differences in SSc clinical features and survival in patients aged > or = 65 years compared with young SSc patients., Methods: Of a total of 319 SSc patients, we identified 67 (21%) patients aged >65 years. Demographical data such as SSc subsets, the cutaneous complaint, internal organ involvement and the causes of morbidity and mortality were collected. Results of the elderly and young patients were compared., Results: There were 61 (91%) women and 6 (9%) men aged > or = 65 years. The limited SSc (lSSc) subset was more prevalent in elderly than in young patients (74.6 vs 54%, P = 0.002). Pulmonary disease (86.6% in elderly vs 73.8% in young patients, P = 0.034) and cardiac involvement (70.1% in elderly vs 49.6% in young patients, P = 0.004) were significantly more prevalent in elderly patients. In contrast, signs of oesophageal involvement (43.3% in elderly vs 57.5% in young patients, P = 0.040) were less frequent in aged patients. In addition, pulmonary and heart disease appeared significantly earlier after the diagnosis in patients aged > or = 65 years. Mortality was significantly higher in elderly than in young patients (35.8 vs 19%, P = 0.005), but when standardized mortality ratios (SMRs) were analysed, there was no significant mortality increase in the elderly., Conclusion: In elderly patients, the lSSc subset is more prevalent than the diffuse. Pulmonary and cardiac involvement are more prevalent in aged patients and appears sooner after the disease diagnosis. SSc is clearly related to increased mortality, although it is not significant in the elderly group.

Objective: To evaluate the diagnostic value of colour-duplex ultrasonography (CDU) of the temporal and ophthalmic arteries in the diagnosis of giant cell arteritis (GCA) and its usefulness in the follow-up of the disease. Furthermore, to examine the relationship between CDU abnormalities in ophthalmic arteries and blindness., Methods: This is a prospective study of all patients with clinical suspicion of GCA or polymyalgia rheumatica (PMR) seen consecutively at the Internal Medicine Department at Vall d'Hebron University Hospital, Spain, between March 2003 and July 2006. Patients were evaluated with regard to the sensitivity and specificity of the dark halo sign in the temporal artery for the diagnosis of GCA, as well as the sensitivity and specificity of the presence of stenosis in temporal and/or ophthalmic arteries. Additionally, the usefulness of the dark halo sign in the follow-up of GCA was addressed., Results: Forty-seven patients (30 with GCA, 17 with PMR) and 13 controls were included in the study. The sensitivity and specificity for the diagnosis of biopsy-proven GCA were higher for the temporal halo (72% in both cases) than for temporal artery stenosis (41% and 89%, respectively), or for ophthalmic artery stenosis (58% and 89%, respectively). Disappearance of the halo was observed in 50% of patients six months after diagnosis, although all patients were in clinical remission, and laboratory parameters were within normal values., Conclusion: CDU of the temporal arteries may be a valid tool in the diagnosis of GCA. However, its role in the follow up of the disease deserves re-evaluation. CDU of the ophthalmic arteries is less useful for CGA diagnosis and no relationship with blindness is suspected.

Objective: Interstitial lung disease (ILD) frequently complicates systemic sclerosis (SSc). Cyclophosphamide (CYC) is a promising immunosuppressive therapy for SSc-related ILD. Our objective was to investigate the effectiveness of an intravenous CYC (iv CYC) pulse regime in SSc-related ILD during treatment and thereafter., Methods: In a prospective observational study ten consecutive patients with SSc-related ILD were treated with iv CYC in a pulse regime lasting from 6 to 24 months. Clinical status, pulmonary functional testing (PFT) and high resolution computed tomography (HRCT) of the chest were evaluated at enrolment and 6, 12 and 24 months thereafter. After treatment withdrawal, patients were followed up every 6 months with PFT and chest HRCT to monitor lung disease., Results: Clinical improvement was apparent in 8 out of 10 patients. The median values of forced vital capacity (FVC), forced expiratory volume in the first second (FEV1) and diffusion lung capacity for carbon monoxide (DLCO) as well as ground-glass pattern on HRCT did not change significantly after 6, 12 and 24 months of therapy. The follow-up continued in 8 out of 10 patients after treatment withdrawal for a median of 26.5 months (range: 12-48 months). The final median FVC was 54.5% of predicted value (interquartile range, IQR= 31.6%-94%). Only one patient suffered a FVC deterioration greater than 10%, even though less than 160 ml. The final median DLCO was 68% of predicted value (IQR=38.3-83.6%). Only 2 patients who developed pulmonary arterial hypertension deteriorated their DLCO values of more than 15%., Conclusions: An iv CYC pulse regimen over 24 months may stabilize pulmonary activity in patients with SSc-related ILD during the course of treatment and for a median of 26.5 months thereafter.