Clinical spectrum time course in non-Asian patients positive for anti-MDA5 antibodies.

OBJECTIVES: To define the clinical spectrum time-course and prognosis of non-Asian patients positive for anti-MDA5 antibodies. METHODS: We conducted a multicentre, international, retrospective cohort study. RESULTS: 149 anti-MDA5 positive patients (median onset age 53 years, median disease duration 18 months), mainly females (100, 67%), were included. Dermatomyositis (64, 43%) and amyopathic dermatomyositis (47, 31%), were the main diagnosis; 15 patients (10%) were classified as interstitial pneumonia with autoimmune features (IPAF) and 7 (5%) as rheumatoid arthritis. The main clinical findings observed were myositis (84, 56%), interstitial lung disease (ILD) (108, 78%), skin lesions (111, 74%), and arthritis (76, 51%). The onset of these manifestations was not concomitant in 74 cases (50%). Of note, 32 (21.5%) patients were admitted to the intensive care unit for rapidly progressive-ILD, which occurred in median 2 months from lung involvement detection, in the majority of cases (28, 19%) despite previous immunosuppressive treatment. One-third of patients (47, 32% each) was ANA and anti-ENA antibodies negative and a similar percentage was anti-Ro52 kDa antibodies positive. Non-specific interstitial pneumonia (65, 60%), organising pneumonia (23, 21%), and usual interstitial pneumonia-like pattern (14, 13%) were the main ILD patterns observed. Twenty-six patients died (17%), 19 (13%) had a rapidly progressive-ILD. CONCLUSIONS: The clinical spectrum of the anti-MDA5 antibodies-related disease is heterogeneous. Rapidly-progressive ILD deeply impacts the prognosis also in non-Asian patients, occurring early during the disease course. Anti-MDA5 antibody positivity should be considered even when baseline autoimmune screening is negative, anti-Ro52 kDa antibodies are positive, and radiology findings show a NSIP pattern.

Abatacept in interstitial lung disease associated with rheumatoid arthritis: national multicenter study of 263 patients.

OBJECTIVE: To assess the efficacy of abatacept (ABA) in RA patients with interstitial lung disease (ILD) (RA-ILD). METHODS: This was an observational, multicentre study of RA-ILD patients treated with at least one dose of ABA. ILD was diagnosed by high-resolution CT (HRCT). We analysed the following variables at baseline (ABA initiation), 12 months and at the end of the follow-up: Modified Medical Research Council (MMRC) scale (1-point change), forced vital capacity (FVC) or diffusion lung capacity for carbon monoxide (DLCO) (improvement or worsening ≥10%), HRCT, DAS on 28 joints evaluated using the ESR (DAS28ESR) and CS-sparing effect. RESULTS: We studied 263 RA-ILD patients [150 women/113 men; mean (s.d.) age 64.6 (10) years]. At baseline, they had a median duration of ILD of 1 (interquartile range 0.25-3.44) years, moderate or severe degree of dyspnoea (MMRC grade 2, 3 or 4) (40.3%), FVC (% of the predicted) mean (s.d.) 85.9 (21.8)%, DLCO (% of the predicted) 65.7 (18.3) and DAS28ESR 4.5 (1.5). The ILD patterns were: usual interstitial pneumonia (UIP) (40.3%), non-specific interstitial pneumonia (NSIP) (31.9%) and others (27.8%). ABA was prescribed at standard dose, i.v. (25.5%) or s.c. (74.5%). After a median follow-up of 12 (6-36) months the following variables did not show worsening: dyspnoea (MMRC) (91.9%); FVC (87.7%); DLCO (90.6%); and chest HRCT (76.6%). A significant improvement of DAS28ESR from 4.5 (1.5) to 3.1 (1.3) at the end of follow-up (P < 0.001) and a CS-sparing effect from a median 7.5 (5-10) to 5 (2.5-7.5) mg/day at the end of follow-up (P < 0.001) was also observed. ABA was withdrawn in 62 (23.6%) patients due to adverse events (n = 30), articular inefficacy (n = 27), ILD worsening (n = 3) and other causes (n = 2). CONCLUSION: ABA may be an effective and safe treatment for patients with RA-ILD.

Late-onset Cogan's syndrome associated with large-vessel vasculitis.

Cogan's syndrome is a rare autoimmune disease that usually affects young Caucasian adults and is classically defined as the combination of nonsyphilitic interstitial keratitis and audiovestibular symptoms resembling Meniere's disease, both of them developed in an interval of less than two years. Nevertheless, cases with atypical ophthalmologic and audiovestibular features, with systemic manifestations or affecting children and older patients have also been reported, expanding the clinical spectrum of Cogan's syndrome. Herein, we present the case of a late-onset Cogan's syndrome associated with a large-vessel vasculitis.

Risk of hospitalization associated with body mass index and weight changes among prevalent haemodialysis patients.

The impact of body mass index (BMI) and body weight on hospitalization rates in haemodialysis patients is unknown. This study hypothesizes that being either underweight or obese is associated with a higher hospitalization rate. Observational study of 6296 European haemodialysis patients with prospective data collection and follow-up every six months for three years (COSMOS study). The risk of being hospitalized was estimated by a time-dependent Cox regression model and the annual risk (incidence rate ratios, IRR) by Poisson regression. We considered weight loss, weight gain and stable weight. Weight change analyses were also performed after patient stratification according to their baseline BMI. A total of 3096 patients were hospitalized at least once with 9731 hospitalizations in total. The hospitalization incidence (fully adjusted IRR 1.28, 95% CI [1.18-1.39]) was higher among underweight patients (BMI <20kg/m2) than patients of normal weight (BMI 20-25kg/m2), while the incidence of overweight (0.88 [0.83-0.93]) and obese patients (≥30kg/m2, 0.85 [0.79-0.92]) was lower. Weight gain was associated with a reduced risk of hospitalization. Conversely, weight loss was associated with a higher hospitalization rate, particularly in underweight patients (IRR 2.85 [2.33-3.47]). Underweight haemodialysis patients were at increased risk of hospitalization, while overweight and obese patients were less likely to be hospitalized. Short-term weight loss in underweight individuals was associated with a strikingly high hospitalization rate.

Anti-MDA5 dermatomyositis mimicking psoriatic arthritis.

Dermatomyositis causes inflammation and damage of muscle and skin, and sometimes involves internal organs, especially lung parenchyma. Patients with dermatomyositis still represent a diagnostic challenge because of the rarity of this disease and the lack of specificity of some of its cutaneous manifestations. Herein, we describe the case of a patient with dermatomyositis, initially diagnosed as psoriatic arthritis, in which the performance of anti-melanoma differentiation-associated gene 5 (MDA5) antibodies was decisive to establish a definitive diagnosis.

Restrictive Use of Oral Glucocorticoids in Systemic Lupus Erythematosus and Prevention of Damage Without Worsening Long-Term Disease Control: An Observational Study.

OBJECTIVE: To analyze the influence of 2 different treatment strategies on general and specific damage accrual in patients with systemic lupus erythematosus (SLE). METHODS: Two cohorts were identified according to the responsible physicians: patients treated at the autoimmune diseases unit (ADU), and patients treated by other members of the internal medicine (IM) department. Members of the ADU worked with a protocol including the universal prescription of hydroxychloroquine (HCQ), the use of maximum oral prednisone dosages ≤30 mg/day and maintenance therapy with ≤5 mg/day, by using methylprednisolone pulses and/or early immunosuppressive (IS) drugs. We analyzed the influence of these 2 treatment strategies on damage accrual, both general and domain specific, attributed to glucocorticoids, cardiovascular (CV) disease, SLE, and unclassified, since the diagnosis of disease in patients with a followup ≥5 years. RESULTS: A total of 74 patients were included in the ADU group and 213 in the IM group. They were comparable for most demographic and lupus-related variables. ADU patients received prednisone later and at lower doses, more methylprednisolone pulses, earlier IS drugs and more HCQ (P < 0.05 for all comparisons). The Systemic Lupus Erythematosus Disease Activity Index score decreased similarly in both cohorts (P = 0.4). Patients in the ADU group were less likely to accrue any damage (P = 0.007). They accrued less glucocorticoid-related (adjusted hazard ratio [HR] 0.23 [95% confidence interval (95% CI) 0.07-0.80]), CV disease (adjusted HR 0.28 [95% CI 0.08-0.95]), and unclassified damage (adjusted HR 0.58 [95% CI 0.3-1.1]). Both groups accrued similar SLE-related damage (adjusted HR 0.84 [95% CI 0.40-1.75]). CONCLUSION: The use of reduced oral prednisone doses, which was possible by combining different therapies, reduced glucocorticoid-related damage and improved CV prognosis without increasing damage caused by SLE.

Patterns of drug therapy in newly diagnosed Spanish patients with systemic lupus erythematosus.

OBJECTIVES: This is the first Spanish multicentric inception lupus cohort, formed by SLE patients attending Spanish Internal Medicine Services since January 2009. We aimed to analyse drug therapy during the first year of follow-up according to disease severity. METHODS: 223 patients who had at least one year of follow-up were enrolled upon diagnosis of SLE. Therapy with prednisone, pulse methyl-prednisolone, hydroxychloroquine, immunosuppressives and calcium/vitamin D was analysed. RESULTS: Prednisone was given to 65% patients, at a mean (SD) daily dose of 11 (10) mg/d. 38% patients received average doses >7.5 mg/d during the first year. Patients with nephritis and with a SLEDAI ≥6 were treated with higher doses of prednisone. 81% of patients were treated with hydroxychloroquine, with higher frequency among those with a SLEDAI ≥6 (88% vs. 68%, p<0.001). The use of immunosuppressive drugs and methyl-prednisolone pulses was higher in patients with a baseline SLEDAI ≥6, however, differences were no longer significant when patients with lupus nephritis were excluded. The use of calcium/vitamin D increased with the dose of prednisone, however, 43% of patients on medium-high doses of prednisone did not take any calcium or vitamin D. CONCLUSIONS: This study gives a real-world view of the current therapeutic approach to early lupus in Spain. The generalised use of hydroxychloroquine is well consolidated. There is still a tendency to use prednisone at medium to high doses. Pulse methyl-prednisolone and immunosuppressive drugs were used in more severe cases, but not as steroid sparing agents. Vitamin D use was suboptimal.

Sarcoidosis-lymphoma syndrome. / Síndrome sarcoidosis-linfoma.

A 65 year-old female with a history of sarcoidosis with pulmonary and joint involvement, who after 5 years of diagnosis begins with central nervous system involvement manifesting as diplopia. She presents normal analysis results. In imaging results, a mass is identified in the right intraconal space; it depends of right optic nerve, and shows multiple lymph node involvement. Biopsy was performed diagnosed with large B-cell lymphoma, an atypical form of tumor associated with sarcoidosis.

Increased Levels of Modified Advanced Oxidation Protein Products Are Associated with Central and Peripheral Blood Pressure in Peritoneal Dialysis Patients.

UNLABELLED: ♦ BACKGROUND AND AIMS: Oxidative stress plays an important role in the pathogenesis of cardiovascular disease (CVD). Central blood pressure (BP) is thought to be more relevant than peripheral BP for the pathogenesis of CVD. Advanced oxidation protein products (AOPP) are markers of oxidative stress. This study investigated the relationship between AOPP and central BP in peritoneal dialysis (PD) patients. ♦ METHODS: In a cross-sectional study of 75 PD patients (67% men), we analyzed two oxidative stress markers, AOPP (modified assay, mAOPP, correcting for the impact of triglycerides) and pentosidine, three inflammation markers, interleukin-6 (IL-6), tumor necrosis factor (TNF), and high-sensitivity C-reactive protein (hs-CRP). All patients underwent measurement of central systolic blood pressure (SBP) and diastolic blood pressure (DBP) by applanation tonometry. ♦ RESULTS: Patients with mAOPP levels above the median had a higher central SBP and DBP than those below the median values. In univariate analysis, the levels of mAOPP associated with central SBP and central DBP. Multiple regression analysis, adjusting for age, gender, diabetes, CVD, protein-energy wasting (PEW), hs-CRP and extracellular water by multi-frequency bioimpedance or N-terminal prohormone of brain natriuretic peptide (NT-proBNP), confirmed independent associations between mAOPP and central SBP and central DBP respectively. ♦ CONCLUSIONS: The mAOPP level is independently associated with the central SBP and DBP in PD patients. This finding suggests that oxidative stress may be involved in the pathogenesis of hypertension or that hypertension itself or factors associated with hypertension such as fluid overload may have an additional effect on oxidative stress in PD patients.

Glucocorticoids and irreversible damage in patients with systemic lupus erythematosus.

OBJECTIVE: The aim of this study was to analyse the relationship between glucocorticoids and damage accrual in SLE. METHODS: We report an observational cohort study including 230 patients with SLE enrolled at diagnosis with 5 years of follow-up. Damage was calculated using the SLICC damage index. Glucocorticoid-related damage was defined as avascular osteonecrosis, osteoporotic fractures, diabetes mellitus or cataracts. Prednisone doses were calculated at the end of the fourth year of follow-up (prednisone-4). A categorical prednisone-4 variable was constructed: no prednisone, ≤7.5 mg/day (low dose), >7.5 mg/day (medium-high dose). The relationship between methylprednisolone pulses and damage was also tested. RESULTS: By the fifth year, 188 patients (82%) had been treated with prednisone. Eighty-seven patients (37.8%) had accrued damage at 5 years. Patients with damage at year 5 had received a higher mean daily prednisone-4 dose (10.4 vs 6 mg/day, P < 0.001). The mean daily prednisone-4 dose was higher in patients accruing glucocorticoid-attributable damage (11 vs 7 mg/day, P = 0.04). Patients taking medium-high doses of prednisone-4 had a higher risk of accruing damage than those taking no prednisone [adjusted odds ratio (OR) 5.39, 95% CI 1.59, 18.27]. Patients taking medium-high doses of prednisone-4 were more likely to develop glucocorticoid-related damage than those on no prednisone (adjusted OR 9.9, 95% CI 1.1, 84). No differences were seen between patients on low doses and those on no prednisone. The cumulative dose of i.v. methylprednisolone-4 was not associated with global or glucocorticoid-related damage. CONCLUSION: Prednisone causes damage in SLE. Doses <7.5 mg/day and methylprednisolone pulses are not associated with damage accrual.

Common and specific associations of anti-SSA/Ro60 and anti-Ro52/TRIM21 antibodies in systemic lupus erythematosus.

Little information exists about the association of anti-SSA/Ro60 and anti-Ro52/TRIM21 with systemic lupus erytematosus (SLE) features. In this work, we analysed the associations of both anti-Ro reactivities with clinical and immunological manifestations in 141 SLE patients. Photosensitivity and xerophtalmia/xerostomia were found to be positively associated with both anti-SSA/Ro60 (P = 0.024 and P = 0.019, resp.) and anti-Ro52/TRIM21 (P = 0.026 and P = 0.022, resp.). In contrast, a negative association was detected regarding anti-phospholipid antibodies, anti-SSA/Ro60 having a stronger effect (P = 0.014) than anti-Ro52/TRIM21. Anti-SSA/Ro60 showed a specific positive association with hypocomplementemia (P = 0.041), mainly with low C4 levels (P = 0.008), whereas anti-Ro52/TRIM21 was found to be positively associated with Raynaud's phenomenon (P = 0.026) and cytopenia (P = 0.048) and negatively associated with anti-dsDNA (P = 0.013). Lymphocytes are involved in the relationship between anti-Ro52/TRIM21 and cytopenia since positive patients showed lower cell levels than negative patients (P = 0.036). In conclusion, anti-SSA/Ro60 and anti-Ro52/TRIM21 showed both common and specific associations in SLE. These data thus increase evidence of the different associations of the two anti-Ro specificities even in a particular disease.

Influence of body mass index on the association of weight changes with mortality in hemodialysis patients.

BACKGROUND AND OBJECTIVES: A high body mass index (BMI) is associated with lower mortality in patients undergoing hemodialysis. Short-term weight gains and losses are also related to lower and higher mortality risk, respectively. The implications of weight gain or loss may, however, differ between obese individuals and their nonobese counterparts. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The Current Management of Secondary Hyperparathyroidism: A Multicenter Observational Study (COSMOS) is an observational study including 6797 European hemodialysis patients recruited between February 2005 and July 2007, with prospective data collection every 6 months for 3 years. Time-dependent Cox proportional hazard regressions assessed the effect of BMI and weight changes on mortality. Analyses were performed after patient stratification according to their starting BMI. RESULTS: Among 6296 patients with complete data, 1643 died. At study entry, 42% of patients had a normal weight (BMI, 20-25 kg/m(2)), 11% were underweight, 31% were overweight, and 16% were obese (BMI ≥ 30 kg/m(2)). Weight loss or gain (<1% or >1% of body weight) was strongly associated with higher rates of mortality or survival, respectively. After stratification by BMI categories, this was true in nonobese categories and especially in underweight patients. In obese patients, however, the association between weight loss and mortality was attenuated (hazard ratio, 1.28 [95% confidence interval (CI), 0.74 to 2.14]), and no survival benefit of gaining weight was seen (hazard ratio, 0.98 [95% CI, 0.59 to 1.62]). CONCLUSIONS: Assuming that these weight changes were unintentional, our study brings attention to rapid weight variations as a clinical sign of health monitoring in hemodialysis patients. In addition, a patient's BMI modifies the strength of the association between weight changes with mortality.

Nonthyroidal illness: a risk factor for coronary calcification and arterial stiffness in patients undergoing peritoneal dialysis?

OBJECTIVES: Low triiodothyronine levels, as part of the nonthyroidal illness syndrome, are common in dialysis patients and have repeatedly been shown to be associated with increased (cardiovascular) mortality rates. We hypothesized that increased vascular calcification may mediate this relationship. METHODS: A total of 84 patients from the Stockholm region receiving maintenance peritoneal dialysis were included in the study. Serum concentrations of free triiodothyronine (fT3), thyroxine and thyroid-stimulating hormone were measured. Coronary artery calcium (CAC) scores were assessed by cardiac computed tomography scans. Surrogates of arterial stiffness included aortic diastolic and systolic blood pressures, pulse pressure, augmentation pressure and Buckberg's subendocardial viability ratio measured by pulse waveform analyses. Patients were subsequently followed, and events of death and censoring were recorded. Thyroid hormone concentrations were associated with CAC scores, measures of arterial stiffness and all-cause mortality. The associations between CAC scores and arterial stiffness surrogates and mortality were also determined to evaluate a possible causal pathway. RESULTS: Both CAC scores and arterial stiffness surrogates were substantially higher in individuals with low fT3 levels. These associations persisted in multivariate logistic and linear regression analyses. During a median (interquartile range) follow-up of 32 (22-42) months, 24 patients died. Both fT3 levels below the median value [HR crude 4.1, 95% confidence interval (CI) 1.4-12.6] and CAC scores above the median value (HR crude 5.8, 95% CI 1.7-20.1) were strongly associated with mortality. CONCLUSIONS: In patients undergoing peritoneal dialysis, fT3 levels were strongly associated with arterial stiffness, coronary artery calcification and mortality. We speculate that the association between nonthyroidal illness and mortality may be partly mediated by acceleration of vascular calcification.

COSMOS: the dialysis scenario of CKD-MBD in Europe.

BACKGROUND: Chronic kidney disease-mineral and bone disorders (CKD-MBD) are important complications of CKD5D patients that are associated with mortality. METHODS: COSMOS is a multicentre, open cohort, prospective, observational 3-year study carried out in haemodialysis patients from 20 European countries during 2005-07. The present article describes the main characteristics of the European dialysis population, the current practice for the prevention, diagnosis and treatment of secondary hyperparathyroidism and the differences across different European regions. RESULTS: The haemodialysis population in Europe is an aged population (mean age 64.8±14.2 years) with a high prevalence of diabetes (29.5%) and cardiovascular disease (76.0%), and 28.7% of patients have been on haemodialysis more than 5 years. Patients from the former Eastern countries are younger (59.3±14.3 versus 66.0±13.9), having a lower proportion of diabetics (24.1 versus 30.7%). There were relevant differences in the frequency of measurement of the main CKD-MBD biochemical parameters [Ca, P and parathyroid hormone (PTH)] and the Eastern countries showed a poorer control of these biochemical parameters (K/DOQI and K/DIGO targets). Overall, 48.0% of the haemodialysis patients received active vitamin D treatment. Calcitriol use doubled that of alfacalcidiol in the Mediterranean countries, whereas the opposite was found in the non-Mediterranean countries. The criteria followed to perform parathyroidectomy were different across Europe. In the Mediterranean countries, the level of serum PTH considered to perform parathyroidectomy was higher than in non-Mediterranean countries; as a result, in the latter, more parathyroidectomies were performed in the year previous to inclusion to COSMOS. CONCLUSIONS: The COSMOS baseline results show important differences across Europe in the management of CKD-MBD.

Vascular calcification in patients with chronic kidney disease: types, clinical impact and pathogenesis.

Vascular calcification plays a major role in cardiovascular disease, which is one of the main causes of mortality in chronic kidney disease patients. Vascular calcification is determined by prevalent traditional and uraemia-related (non-traditional) risk factors. It occurs mainly in the arteries, which are classified into three types according to their size and structural characteristics. In addition, vascular calcification has been associated with bone loss and fractures in chronic kidney disease patients and the general population, stressing the fact that both disorders can share pathogenetic pathways. The strategies to control vascular calcification involve several measures, chief among them the control of hyperphosphataemia. Furthermore, it has been recently described that strategies that reduce bone resorption and increase bone mineralization may decrease the risk of vascular calcifications; however, this approach still remains controversial. The mechanisms involved in vascular calcification are complex and not yet fully understood. Phosphorus plays a major role, while other factors related to bone formation have been recently identified.