RESUMEN

BACKGROUND: Scientific guidelines have been developed to update and harmonize exercise based cardiac rehabilitation (ebCR) in German speaking countries. Key recommendations for ebCR indications have recently been published in part 1 of this journal. The present part 2 updates the evidence with respect to contents and delivery of ebCR in clinical practice, focusing on exercise training (ET), psychological interventions (PI), patient education (PE). In addition, special patients' groups and new developments, such as telemedical (Tele) or home-based ebCR, are discussed as well. METHODS: Generation of evidence and search of literature have been described in part 1. RESULTS: Well documented evidence confirms the prognostic significance of ET in patients with coronary artery disease. Positive clinical effects of ET are described in patients with congestive heart failure, heart valve surgery or intervention, adults with congenital heart disease, and peripheral arterial disease. Specific recommendations for risk stratification and adequate exercise prescription for continuous-, interval-, and strength training are given in detail. PI when added to ebCR did not show significant positive effects in general. There was a positive trend towards reduction in depressive symptoms for "distress management" and "lifestyle changes". PE is able to increase patients' knowledge and motivation, as well as behavior changes, regarding physical activity, dietary habits, and smoking cessation. The evidence for distinct ebCR programs in special patients' groups is less clear. Studies on Tele-CR predominantly included low-risk patients. Hence, it is questionable, whether clinical results derived from studies in conventional ebCR may be transferred to Tele-CR. CONCLUSIONS: ET is the cornerstone of ebCR. Additional PI should be included, adjusted to the needs of the individual patient. PE is able to promote patients self-management, empowerment, and motivation. Diversity-sensitive structures should be established to interact with the needs of special patient groups and gender issues. Tele-CR should be further investigated as a valuable tool to implement ebCR more widely and effectively.

RESUMEN

Pain in the musculoskeletal system and in the joints is what comes to mind first when people talk about rheumatic diseases. However, rheumatic diseases are multisystem disorders that can affect every organ system. Therefore, ocular manifestations are common and can occur in almost every rheumatic disease. On the one hand, they can even precede musculoskeletal manifestations. On the other hand, they can remain unrecognized without a thorough ophthalmologic examination in some disease entities. Consequently, a close cooperation between medical specialties is warranted, to prevent permanent impairment in vision or consequential damage to organs or joints.The following article thus focuses on the most important ocular manifestations of rheumatic diseases. For example, we address keratoconjunctivitis sicca as a complication in many rheumatic disorders, which include rheumatoid arthritis and, most importantly, Sjogren's syndrome. Furthermore, we cover uveitis and associated diseases such as spondyloarthritis or sarcoidosis. Also, we discuss giant cell arteritis as a rheumatological emergency. All in all, we aim to give a synopsis of clinical presentations, important diagnostic measures, and current therapeutic options of the above-mentioned disorders.

Asunto(s)

RESUMEN

OBJECTIVE: Autoantibodies against CD74 (anti-CD74) are associated with ankylosing spondylitis (AS). The present multicenter study, the International Spondyloarthritis Autoantibody (InterSpA) trial, was undertaken to compare the sensitivity and specificity of anti-CD74 and HLA-B27 in identifying patients with nonradiographic axial spondyloarthritis (axSpA). METHODS: Patients ages 18-45 years with inflammatory back pain of ≤2 years' duration and a clinical suspicion of axSpA were recruited. HLA-B27 genotyping and magnetic resonance imaging of sacroiliac joints were performed in all patients. One hundred forty-nine patients with chronic inflammatory back pain (IBP) not caused by axSpA served as controls, and additional controls included 50 AS patients and 100 blood donors whose specimens were analyzed. RESULTS: One hundred patients with inflammatory back pain received a diagnosis of nonradiographic axSpA from the investigators and fulfilled the Assessment of SpondyloArthritis international Society (ASAS) criteria. The mean age was 29 years, and the mean symptom duration was 12.5 months. The sensitivity of IgA anti-CD74 and IgG anti-CD74 for identifying the 100 axSpA patients was 47% and 17%, respectively. The specificity of both IgA anti-CD74 and IgG anti-CD74 was 95.3%. The sensitivity of HLA-B27 was 81%. The positive likelihood ratios were 10.0 (IgA anti-CD74), 3.6 (IgG anti-CD74), and 8.1 (HLA-B27). Assuming a 5% pretest probability of axSpA in chronic back pain patients, the posttest probability, after consideration of the respective positive test results, was 33.3% for IgA anti-CD74, 15.3% for IgG anti-CD74, and 28.8% for HLA-B27. A combination of IgA anti-CD74 and HLA-B27 results in a posttest probability of 80.2%. CONCLUSION: IgA anti-CD74 may be a useful tool for identifying axSpA. The diagnostic value of the test in daily practice requires further confirmation.

Asunto(s)

RESUMEN

PURPOSE: TNF alpha inhibitors have revolutionized the care of vision-threatening uveitis. This study evaluated the efficacy of adalimumab (ADA) for the treatment of refractory noninfectious uveitis. DESIGN: Randomized, prospective, controlled, two-center clinical trial Methods: Patients with active uveitis despite combined oral low-dose prednisolone and immunosuppression were randomized for additional ADA with corticosteroids in a fixed tapering regime, or corticosteroids only. Primary outcome measure at three months was improved best-corrected visual acuity (BCVA; >2 lines). In case of treatment failure, switch to the other arm was possible. RESULTS: Twenty-five patients (10 ADA, 15 controls) were included. BCVA increased with ADA by > 2 lines in 6/10 patients (60%; mean increase of 0.23 logMAR), but in only 2/15 from controls (13%, mean increase of 0.04 logMAR, Fisher´s exact test p = 0.00221). CONCLUSIONS: The results show superiority of ADA over controls in severe ocular inflammation including anterior uveitis.

Asunto(s)

RESUMEN

Regulatory T cells (Tregs) are critical mediators of immune tolerance, yet their involvement in the autoimmune disease systemic lupus erythematosus (SLE) is incompletely understood. We analyzed CD4+ T cell subpopulations with Treg-related phenotypes and their association with disease activity in peripheral blood (PB) and tissues of patients with SLE. In detail, we quantified subpopulations regarding CD25, FOXP3, CD62L, CCR6, CD27, CD45RA, and CD45RO expression in PB from 31 patients with SLE divided into two disease activity groups and 32 healthy controls using flow cytometry. CD4+ and FOXP3+ T cells in skin and kidney biopsies of patients with SLE were quantified by immunohistochemistry. CD4+CD25+/++FOXP3+ and CD4+CD25+CD45RA-/CD45RO+ T cell frequencies were significantly higher in PB from patients with active compared to inactive SLE. The fraction of CD4+CD25++FOXP3+ Tregs and CD4+CD25+CD45RA+/CD45RO- naïve Tregs was not significantly different between these groups. CD4+CD25++ Tregs from active SLE patients comprised significantly less CD27+ cells and more CCR6+ cells compared to patients with inactive SLE. The percentage of CD4+FOXP3+ T cells among inflammatory infiltrates in skin and kidney biopsies of SLE patients was not different from other inflammatory skin/kidney diseases. In conclusion, although CD4+FOXP3+ T cell frequencies in the inflamed tissues of SLE patients were comparable to other inflammatory diseases, distinct T cell subpopulations appeared misbalanced in PB of patients with active SLE. Here, cells phenotypically resembling activated T cells, but not Tregs, were increased compared to patients with inactive SLE. Within Tregs of patients with active SLE, markers related to Treg function and homing were altered.

Asunto(s)

RESUMEN

Acquired amegakaryocytic thrombocytopenic purpura (AATP) is a rare hematological disorder characterized by severe thrombocytopenia and a complete or near-to complete absence of megakaryocytes in the bone marrow, while granulopoiesis, as well as erythropoiesis are usually preserved. Although autoimmune mechanisms are believed to be causative, the exact underlying pathogenesis is not known. To date, only few cases have been reported and management of this disease remains controversial with immunosuppression being the treatment modality of choice in the majority of patients. In this article, we report a case of newly acquired AATP without an associated autoimmune disease, refractory to corticoids, intravenous immunoglobulin (IVIG) and second-generation TPO (thrombopoietin) agonists, which have recently been approved for the treatment of thrombocytopenia. Finally, in accordance with other reports, disease progression into aplastic anemia has occurred.

Asunto(s)

RESUMEN

OBJECTIVE: Rituximab (RTX) has been used successfully for the treatment of severe Jo1 antibody-associated antisynthetase syndrome. The aim of this retrospective study was to evaluate the effect of RTX in severe Jo1 antisynthetase syndrome and determine predictive factors for response. METHODS: There were 61 patients with Jo1 antisynthetase syndrome identified; 18 of these received RTX. One patient was lost to followup. The remaining 17 patients and 30 out of 43 patients who were treated with conventional immunosuppressive (IS) drugs were followed for a mean of 35 months and 84 months, respectively. RESULTS: Polymyositis/dermatomyositis (95%) and interstitial lung disease (ILD; 66%) were the dominant clinical manifestations. Detection of anti-Ro52 antibodies (43%) was significantly associated with acute-onset ILD (p = 0.016) with O2 dependency, and patients with high concentrations of anti-Ro52 (20%) had the highest risk (p = 0.0005). Sixteen out of 18 patients (89%) showed a fast and marked response to RTX. Among those patients who were highly positive for anti-Ro52, response to RTX was seen in 7 out of 7 cases (100%), but no response to cyclophosphamide (n = 4), cyclosporine A (n = 3), azathioprine (n = 9), methotrexate (n = 5), or leflunomide (n = 2) was observed. One patient treated with RTX died of pneumonia. CONCLUSION: RTX is effective in the treatment of severe forms of Jo1 antisynthetase syndrome. In our retrospective study, the presence of high anti-Ro52 antibody concentrations predicts severe acute-onset ILD and nonresponse to IS drugs. In contrast to conventional IS, RTX is equally effective in patients with Jo1 antisynthetase syndrome, independent of their anti-Ro52 antibody status.

Asunto(s)

RESUMEN

BACKGROUND: Most ocular changes in pregnancy are harmless. For example, 14% of pregnant women need a new eyeglass prescription. Some changes, however, are serious, such as retinal effects of hypertension, which can be a sign of pre-eclampsia. Ocular changes may give rise to uncertainty about the administration of ophthalmological drugs or the optimal method of childbirth. METHOD: This review is based on pertinent literature retrieved by a selective search in Medline and on guidelines from Germany and abroad. Recommendations about drugs were taken from the Embryotox and Reprotox databases, the German Red List, and the United States Food and Drug Administration (FDA). RESULTS: 40% to 100% of pregnant women with high blood pressure have retinal changes whose severity is correlated with the severity of pre-eclampsia or eclampsia. Diabetic women should undergo ocular examination before and during pregnancy. Pre-existing retinal changes worsen during pregnancy in 55% of cases. Most ocular diseases can be treated with the usual drugs in pregnant women and nursing mothers, although the evidence for drug safety is derived from case series and the treatment is usually provided off label. Ocular conditions that are present before pregnancy are irrelevant to the choice of a method of childbirth. CONCLUSION: Pregnant women and nursing mothers can undergo most types of ophthalmological examination and treatment. Recommendations about drug treatment should be checked against current information that can be found on the embryotox.de and reprotox.de websites.

Asunto(s)

RESUMEN

OBJECTIVE: B cells with immunoregulatory properties (Breg cells) have been described in mice, but their role in the control of human immune responses is not well defined. We recently identified a human population of activated FSC(high) B cells that exhibited regulatory activity toward T helper cells. The aim of the present study was to test such induced Breg (iBreg) cells in patients with autoimmune disease. METHODS: Purified CD19+FSC(high) B cells derived from patients with systemic lupus erythematosus (SLE) or from healthy donors, which were activated via their B cell receptor, were cocultured with CD3-stimulated CD4+ T helper cells from SLE patients or healthy donors. (3) H-thymidine incorporation, flow cytometry, and enzyme-linked immunosorbent assay (ELISA) were used to analyze proliferation, cytokine secretion, and surface marker expression. RESULTS: Although under costimulatory conditions, FSC(high) SLE B cells supported the proliferation of healthy donor T cells to a similar extent as donor B cells, their regulatory function was significantly diminished in B cell suppressor assays. Similar effects were seen when SLE T cells were used, confirming that SLE T cells were equally susceptible to iBreg cell signals as healthy donor T cells and that SLE iBreg cell defects were independent of T cell origin. B cell viability and expression of surface markers (CD25, CD80, and B7-H1) or cytokines (interleukin-6 [IL-6], tumor necrosis factor α, and IL-10) were comparable in the two B cell populations. There was no correlation between the extent of iBreg cell-induced inhibition and disease activity. CD19+FSC(high) B cells from patients with another systemic autoimmune disease, granulomatosis with polyangiitis (Wegener's) (GPA), exhibited no regulatory defects, which suggests that the iBreg cell defects were SLE-specific and not a general consequence of autoimmunity or inflammation. CONCLUSION: Induced Breg cells from SLE patients, but not GPA patients, are less effective in the control of T helper cell proliferation, which supports the reported skewed B cell repertoire in SLE. The malfunctioning SLE iBreg cells might allow the overstimulation of immune responses and contribute to the initiation and/or perpetuation of disease.

Asunto(s)

RESUMEN

OBJECTIVE: Patients with RA suffer from a higher risk of periodontal attachment loss and increased oral inflammation. We hypothesize that there are pathogenetic and immunological interactions between these diseases that go beyond impaired manual dexterity accompanying advanced RA. The primary objective of the present study was to determine whether a loss of alveolar bone can be detected in RA patients during the early course of the disease. METHODS: In this cross-sectional, epidemiological case-control study, 22 patients with early RA (ERA) were compared with 22 matched healthy controls. Oral and periodontal status, clinical activity, and socio-demographic parameters were determined. Oral microbiota were analysed using real-time quantitative PCR specific for leading oral pathogens. RESULTS: More advanced forms of periodontitis were found in ERA patients compared with controls. ERA patients had a greater number of missing teeth [ERA 5.7 (s.d. 5.0), controls 1.9 (s.d. 1.0), P = 0.002], deeper periodontal pockets [clinical attachment level: ERA 3.4 (s.d. 0.5 mm), controls 2.7 (s.d. 0.3 mm), P < 0.000], and greater bleeding on probing [ERA 18.6% (s.d. 9.0%), controls 10.5% (s.d. 5.1%), P = 0.001] despite comparable oral hygiene. Tannerella forsythia (6.77-fold, P = 0.033) subgingivally and Streptococcus anginosus (3.56-fold, P = 0.028) supragingivally were the characteristic pathogens in ERA. CONCLUSION: Increased loss of periodontal attachment and alveolar bone can be detected in patients with ERA, therefore we propose that the consulting rheumatologists inform the patients that they have a higher risk of periodontal disease. It would be beneficial if these patients were referred directly for intensive dental care.

Asunto(s)

RESUMEN

OBJECTIVE: To report the efficacy of rituximab (RTX) in the treatment of ocular or orbital inflammation accompanying autoimmune diseases refractory to previous standard immunosuppressive therapy. METHODS: We reviewed medical records of 9 consecutive patients with noninfectious ocular or orbital inflammation treated with RTX. RESULTS: Over a mean followup of 42 months, 7 patients were in clinical remission, 1 had partial response to treatment, and 1 did not respond. Best corrected visual acuity improved ≥ 1 line in 4 patients, was stable in another 4 patients, and worsened in 1. Concomitant immunosuppressive therapy was tapered in 6 cases. Systemic corticosteroids were tapered or kept below 7.5 mg a day in 5 patients 1 year after the first RTX cycle. CONCLUSION: RTX therapy, in patients who are refractory to standard immunosuppressive therapy, was effective and showed a beneficial response to treatment including induction of clinical remission of inflammation in most patients.

Asunto(s)

RESUMEN

PURPOSE: To compare interferon (IFN) beta with methotrexate (MTX) in the treatment of intermediate uveitis with macular edema. DESIGN: Monocentric, prospective, randomized, controlled clinical trial. SETTING: Specialized uveitis center at the University of Heidelberg. PATIENT OR STUDY POPULATION: Patients with either primary intermediate uveitis or uveitis associated with multiple sclerosis. MAIN INCLUSION CRITERIA: Visual acuity of 20/30 or worse (0.2 logarithm of the minimal angle of resolution) and macular edema of more than 250 µm (central 1-mm in optical coherence tomography; Stratus). Randomization into either IFN beta 44 µg subcutaneously 3 times weekly or 20 mg MTX subcutaneously once weekly. MAIN OUTCOME MEASURES: At 3 months, the primary outcome parameter of mean change in visual acuity was evaluated and efficacy was determined. Secondary parameters were macular edema by optical coherence tomography, inflammatory activity, and retinal sensitivity by microperimetry (MP-1; Nidek). In case of treatment failure, switching to the other treatment arm was possible. RESULTS: Nineteen patients were included. Ten were randomized to MTX, and 9 were randomized to IFN beta. At 3 months, visual acuity improved a mean 0.31 logarithm of the minimal angle of resolution (range, -0.02 to -0.96, 15.6 letters on the Early Treatment Diabetic Retinopathy Study chart) in the IFN beta group versus a mean 0.09 logarithm of the minimal angle of resolution (range, 0.12 to -0.38, 4.7 letters) in the MTX arm (P = .0435, Mann-Whitney U test). Macular thickness decreased by a mean of 206 µm (range, -41 to -416 µm) in the IFN arm, but increased by 47 µm (range, 108 to -28 µm) in the MTX group (P < .0001). CONCLUSIONS: Although the sample size is small, results of the trial support superiority of IFN beta over MTX in the treatment of macular edema in the setting of intermediate uveitis.

Asunto(s)

RESUMEN

OBJECTIVE: The aim of this study was to assess the efficacy of adalimumab in patients with active non-infectious uveitis in three different centres. METHODS: In a retrospective study we identified patients from our databases who were treated with adalimumab. The composite outcome measure for efficacy included reduction of macular oedema by optic coherence tomography, visual acuity, anterior chamber cells, reduction of frequency of flares and reduction of prednisone dose during the treatment. At least one of the criteria had to be improved and none worsened to declare treatment as effective. RESULTS: 60 patients with an average age of 37.3 years (range 4-71 years) were treated with adalimumab over an average follow-up period of 87.9 weeks (range 12-222 weeks). The indication for treatment was in 41 (68.3%) patients the activity of both uveitis and systemic disease and in 19 (31.7%) patients uveitis activity only. 15 (25%) patients were treated before with etanercept and 10 (16.7%) patients with infliximab. 49 out of 60 (81.7%) patients improved, while the other 11 (18.3%) patients did not meet improvement criteria and were given additional or alternative immunosuppressive treatment. At the last follow-up, 47 (78.3%) patients were still on adalimumab treatment. 13 (21.6%) patients stopped adalimumab treatment, due to inefficacy in eight, another three patients due to side effects (liver enzyme elevation and furunculosis), one patient due to pregnancy and one patient died. CONCLUSIONS: This large retrospective case series showed that adalimumab is effective in up to 80% of patients with uveitis.

Asunto(s)

RESUMEN

PURPOSE: We aimed to review all uveitis patients with a positive Borrelia serology to evaluate positive results in uveitis subtypes. Further we wanted to test a self-assembled Interferon gamma release assay (IGRA) as a possible supplement method in these patients. METHODS: Patients where serology for Borrelia was ordered from September 2005 to May 2008, were identified by database search. Patients with positive results in ELISA and Western Blot were retested by a self-assembled IGRA. Bayes Theorem was applied. RESULTS: Testing for Borrelia was ordered for 184 patients. 18 patients (9,8%) showed positive results. 11 were positive for IgG (5,9 %), 3 were positive for IgG and IgM (1,6 %) and 4 for IgM (2,1%). Applying Bayes Theorem, we calculated a posttest-probability of 9% in case of a positive test result. 16 of the 18 patients were retested by IGRA. None of them showed a positive result. CONCLUSIONS: A positive serology with uveitis as the only clinical symptom is not sufficient to confirm Borreliosis as 5,9 % of patients with uveitis and a positive IgG serology correspond to the normal spread of Borrelia in the population. Looking at posttest-probability shows a lot of false-positive test results when testing all uveitis patients for Borrelia routinely.

Asunto(s)

RESUMEN

OBJECTIVE: Systemic lupus erythematosus (SLE) is associated with high cardiovascular morbidity and mortality. Cardiovascular involvement is frequently underestimated by routine imaging techniques. Our aim was to determine if new echocardiographic imaging modalities like tissue Doppler (TDI), strain rate (SRR), and strain (SRI) imaging detect abnormalities in left ventricular (LV) function in asymptomatic patients with SLE. METHODS: Sixty-seven young patients with SLE (mean age 42 +/- 10 yrs) without typical symptoms or signs of heart failure or angina, and a matched healthy control group (n = 40), underwent standard transthoracic echocardiography, TDI, SRR, and SRI imaging of the LV as well as assessment of disease characteristics. RESULTS: Despite findings within the normal range on routine standard 2-dimensional echocardiography, SLE was associated with significantly impaired systolic and diastolic myocardial velocities of the LV measured by TDI [mean global TDI: systolic (s): 2.9 +/- 0.9 vs 3.9 +/- 0.7 cm/s, p < 0.05; early (e): 4.3 +/- 1.5 vs 6.3 +/- 1.3 cm/s, p < 0.05; late (a): 2.9 +/- 0.8 vs 3.4 +/- 0.8 cm/s, p < 0.05; values +/- SD); SRR (s: -0.8 +/- 0.1 vs -1.1 +/- 0.1 s(-1); e: 1.1 +/- 0.2 vs 1.6 +/- 0.3 s(-1); a: 0.7 +/- 0.1 vs 1.0 +/- 0.2 s(-1); all p < 0.05); and SR (-15.11 +/- 2.2% vs -19.7 +/- 1.9%; p < 0.05) compared to the control group. Further, elevated disease activity, measured with the ECLAM and the SLEDAI score, resulted in significantly lower values for LV longitudinal function measured by SRR and SR, but not by TDI. CONCLUSION: SLE is associated with a significant impairment of systolic and diastolic LV longitudinal function in patients without cardiac symptoms. New imaging modalities provide earlier insight into cardiovascular involvement in SLE and seem to be superior to standard echocardiography to detect subclinical myocardial disease.

Asunto(s)

RESUMEN

Since their discovery in the 1950s interferons have been the scope of investigation in many diseases as therapeutic as well as pathogenetic factors. We know they have immune stimulatory and immune regulatory effects. This apparently counter-intuitive mechanism can be summarized as immunomodulatory action and seems to be very effective in a number of ocular inflammatory diseases. We review the current knowledge of interferons in immunity and autoimmunity and show their use in clinical ophthalmologic practice.

RESUMEN

A characteristic of apo cell death is the shedding of membrane vesicles from the dying cell. This process is also referred to as apo membrane blebbing. These apo particles contain various autoantigens and are effectively engulfed by phagocytes. A defective phagocytosis has been described in autoimmune diseases like systemic lupus erythematosus and this defect might lead to an accumulation of apo cells and bodies. Thus, we investigated the interactions between apototic cell-derived membrane vesicles (ACdMV), and myeloid dendritic cell (DC). ACdMV were isolated from the supernatant of apo lymphocytes. These isolated ACdMV were morphologically characterized as membrane coated vesicles of an average size of 500 nm. Coincubating isolated ACdMV with iDC we observed CD83 surface expression of the latter. Accumulation of ACdMV may contribute to an inflammatory immune response in autoimmune diseases.

Asunto(s)

Asunto(s)

Asunto(s)