Christof Specker

Self-assessments of patients via Tablet PC in routine patient care: comparison with standardised paper questionnaires

Objective: We evaluated the feasibility of electronic data capture of self-administered patient questionnaires using a Tablet PC for integration in routine patient management; we also compared these data with results received from corresponding paper–pencil versions. Methods: Standardised patient questionnaires (FFbH/HAQ, BASDAI, SF-36) were implemented in our documentation software. 153 outpatients (rheumatoid arthritis, systemic lupus erythematosus, spondyloarthritis) completed sets of questionnaires as paper–pencil and electronic versions using a Tablet PC. The quality and validity of data obtained using a Tablet PC and the capability of disabled patients to handle it were assigned; patients’ experiences, preferences and computer/internet use were also assessed. Results: Scores obtained by direct data entry on the Tablet PC did not differ from the scores obtained by the paper–pencil questionnaires in the complete group and disease subgroups. No major difficulties using the Tablet PC occurred. 62.1% preferred remote data entry in the future. Seven (4.6%) patients felt uncomfortable with the Tablet PC due to their rheumatic disease. Conclusions: Self-administered questionnaires via Tablet PC are a facile and capable option in patients with rheumatic diseases to monitor disease activity, efficacy and safety assessments continuously. Tablet PC applications offers directly available data for clinical decision-making improves quality of care by effective patient monitoring, and contributes to patients’ empowerment.

Low risk of renal flares and negative outcomes in women with lupus nephritis conceiving after switching from mycophenolate mofetil to azathioprine

OBJECTIVE MMF is teratogenic and needs to be replaced before pregnancy. This change may lead to flares. Our aim was to determine the risk of renal flares in women with LN who switched treatment from MMF to AZA before conception and to evaluate the outcome of their pregnancies. METHODS Medical records of women with LN counselled for pregnancy wish were reviewed. Women receiving treatment with either MMF or AZA (control group), with inactive lupus (SLEDAI ≤ 4) and quiescent LN (serum creatinine <1.5 mg/dl, inactive sediment and proteinuria <1 g/24 h for the preceding 6 months) were eligible for this study. RESULTS We identified 54 women [23 treated with MMF (group 1) and 31 treated with AZA (group 2)]. MMF dosage was tapered and subsequently transferred to AZA, which was maintained throughout pregnancy. Three (13%) patients (group 1) vs none (group 2) developed a renal flare 3-6 months after transitioning from MMF to AZA (P = 0.14) before pregnancy ensued. The only parameter with a significant difference in those with flare compared with those without was younger age (median 27 vs 30 years; P = 0.03). Risk for adverse outcome within 48 pregnancies (pre-eclampsia 9%, preterm delivery 20.5%) increased with every milligramme of prednisone dosage [odds ratio (OR) 2.03] and every single unit of SLEDAI score (OR 3.92). Renal flares occurred post-partum in two women. No patient developed worsening of renal function. CONCLUSION Replacing MMF with AZA in patients with quiescent LN for pregnancy planning rarely leads to renal flares. Pregnancy outcome was favourable.

S1-Leitlinie der DGRh zur sequenziellen medikamentösen Therapie der rheumatoiden Arthritis 2012

Following the EULAR recommendations published in 2010 German guidelines for the medical treatment of rheumatoid arthritis were developed based on an update of the systematic literature search and expert consensus. Methotrexate is the standard treatment option at the time of diagnosis, preferably in combination with low dose glucocorticoids. Combined disease-modifying antirheumatic drugs (DMARD) therapy should be considered in patients not responding within 12 weeks. Treatment with biologicals should be initiated in patients with persistent high activity no later than 6 months after conventional treatment and in exceptional situations (e.g. early destruction or unfavorable prognosis) even earlier. If treatment with biologicals remains ineffective, changing to another biological is recommended after 3-6 months. In cases of long-standing remission a controlled reduction of medical treatment can be considered.

Novel 68 kDa autoantigen detected by rheumatoid arthritis specific antibodies.

OBJECTIVE--To improve the understanding of the pathogenesis of rheumatoid arthritis (RA) by identifying novel, disease specific autoantibodies. METHODS--Total protein preparations from synovial membranes were separated electrophoretically and immunoblotted. Sera from RA patients were screened for predominant immunoreactions by blotting. A 68 kDa antigen target of the most predominant reaction was detected and further characterised. RESULTS--The dominant immunoreaction in most of the RA sera tested was with a 68 kDa antigen. The antigen is probably ubiquitously expressed. It has an isoelectric point of 5.1, is O-glycosylated, and is located in the endoplasmic reticulum, the cytoplasm, or both. Antibodies to the 68 kDa autoantigen were present in 64% of 167 RA patients tested, and could also be detected in seronegative RA patients, but were present in only 1% of 98 patients with other rheumatic diseases. They could not be detected in 55 healthy controls. CONCLUSIONS--Because of its high sensitivity (64%) and specificity (99%), the anti-68 kDa autoantibody not only provides another valuable parameter for diagnosis, but also represents an antibody that may be involved in the pathological mechanisms leading to RA. This hypothesis can be tested by investigating if 68 kDa specific T cells are present in RA patients.

Molecular imaging of cartilage damage of finger joints in early rheumatoid arthritis with delayed gadolinium-enhanced magnetic resonance imaging.

OBJECTIVE To assess cartilage glycosaminoglycan content and cartilage thickness in the metacarpophalangeal (MCP) joints of patients with early rheumatoid arthritis (RA) and healthy volunteers. METHODS After review board approval and informed consent were obtained, 22 subjects were prospectively enrolled (9 patients with early RA [7 women and 2 men with a mean ± SD age of 49 ± 13 years; range 25-68 years] and 13 healthy volunteers [10 women and 3 men with a mean ± SD age of 51 ± 12 years; range 25-66 years). In a total of 44 MCP joints of the index and middle fingers, measurements of cartilage thickness and delayed gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) index (T1 [msec]) were obtained using the variable flip-angle method and a 3T MR scanner. MRIs were evaluated for bone edema, erosions, and synovitis (using the RA MRI Scoring criteria). Students t-test was used to test the significance of differences between groups. RESULTS The mean ± SD dGEMRIC index was 497 ± 86 msec in healthy volunteers and was significantly lower in the early RA group (421 ± 76 msec) (P = 0.042). There was no joint space narrowing seen on standard radiographs. No significant difference was found between cartilage thickness in patients with early RA and that in controls (index finger mean ± SD 1.27 ± 0.23 mm in RA patients versus 1.46 ± 0.34 mm in controls [P = 0.16] and middle finger 1.26 ± 0.23 mm in RA patients versus 0.97 ± 0.47 mm in controls [P = 0.10]). No significant correlation was noted between cartilage thickness and dGEMRIC index (R = 0.36, P = 0.88 in RA patients; R = 0.156, P = 0.445 in controls). CONCLUSION Our findings indicate that cartilage damage is present in the MCP joints of patients with early RA despite the absence of joint space narrowing on standard radiographs and MRI. Cartilage damage in RA can be imaged with dGEMRIC.

The p68 autoantigen characteristic of rheumatoid arthritis is reactive with carbohydrate epitope specific autoantibodies

OBJECTIVE The autoantigen p68 is a target of autoantibodies as well as autoreactive T cells with a high specificity in rheumatoid arthritis (RA). The binding characteristics of the autoantibodies to their antigen were now analysed biochemically and cytologically. METHODS Deglycosylation techniques as well as lectin and sugar competition experiments were performed to p68 to discover if the antibodies detected a glycoepitope. Its antigenicity was investigated applying anti-p68 antibodies derived from RA patients in comparison with polyclonal rabbit anti-p68 antibodies. RESULTS p68 specific antibodies from RA patients did not to bind to p68 that had been deglycosylated by alkaline β-elimination, O-glycosidase or periodate treatment. In contrast, binding of p68 specific antibodies raised in rabbit was unaffected by either deglycosylation protocol. Furthermore, lectins specific for the carbohydrate N-acetylglucosamine competed with p68 specific antibodies from RA patients for antigen binding.N-acetylglucosamine by itself also competed with patient derived anti-p68 antibodies for p68 binding. Again, rabbit anti-p68 antibodies did not elicit these competitive effects. Applying cytoimmunofluorescence, p68 was present in the cytoplasm or endoplasmic reticulum and also in low abundance on the cell surface. Under heatshock conditions, p68 was detectable in the nucleus. CONCLUSIONS Autoimmunity to p68 during RA is carried by anti-carbohydrate autoantibodies. The carbohydrate modification of p68 appears to be N-acetylglucosamine, which may reflect the regulation of intracellular localisation of the antigen. It is hypothesised that a shift in glycosylation pattern accompanied by an unphysiological localisation of the antigen could trigger antigenicity of p68 during the pathogenesis of RA.

Rheumatoid arthritis: autoreactive T cells recognising a novel 68k autoantigen

OBJECTIVE A 68k autoantigen has been identified by specific antibodies from patients with rheumatoid arthritis (RA). This study considered whether or not this antigen is a target for T cells and thus may play a part in T cell mediated immunopathology of active RA. METHODS The 68k antigen was isolated and used in a nitrocellulose bound form to stimulate T cells. Proliferation of T lymphocytes of peripheral blood as well as synovial fluid was measured. RESULTS Peripheral blood T cells specifically proliferating against the 68k antigen were detected in 19 of 27 patients with RA (70%). For T cells isolated from peripheral blood, proliferation peaked on day 10. When T cells were isolated from actively inflamed synovial fluid, the proliferation kinetics shifted to a peak on day 3. Blockade of HLA class II antigens resulted in an increase of proliferation in the case of HLA-DP. Applying HLA-DP specific antibodies capable of inhibiting antigen presentation mediated by this molecule, T cells of 17 of 27 RA patients (63%) proliferated to a higher extent than with the 68k antigen alone. The phenomenon that an increased proliferation occurred upon blockade of a particular HLA class II family member was also demonstrated for DQ and DR: the 68k antigen likewise stimulated T cells restricted for DP or DQ, respectively. CONCLUSIONS The novel 68k antigen is a target of both T and B cellular immune responses and as such could play a part in the immune dysfunction of RA. The finding that blocking of certain HLA class II molecules functioning in antigen presentation (for example, via HLA-DQ) results in a higher instead of lower proliferation in vitro, may argue for the presence of antigen specific suppressive T cells.

Pregnancy outcome in patients with antiphospholipid syndrome after cerebral ischaemic events: an observational study

Among the most prominent features associated with antiphospholipid syndrome (APS) are cerebral ischaemic events (CVE). Pregnancy with APS increases the risk of thrombosis, including CVE. This study was undertaken to assess the risk of obstetric complications and recurrence of CVE during pregnancy in women with APS and previous CVE. We prospectively observed 23 pregnancies in 20 women (median age 31 years) with primary (n = 8) or secondary APS (n = 12). Eight patients had transient ischaemic attacks (TIA) and 12 had stroke before pregnancy. All patients received aspirin 100 mg daily in combination with low molecular weight heparin (LMWH) during their pregnancies. The live birth rate was 91.3% (n = 21). Obstetrical complications consisted mainly of preeclampsia (n = 8, 34.8%) and preterm delivery (n = 9, 42.9%). The risk for preeclampsia increased in patients who were positive for multiple antiphospholipid antibodies (aPL) (odds ratio (OR) 3.06 (95% confidence interval (CI) 1.01–9.32)) per positive aPL test (i.e anticardiolipin antibody, anti-ß2-glycoprotein I antibody, lupus anticoagulant) (p 0.049). Three patients experienced recurrent CVE in the context of pregnancy (one during pregnancy, two in the postpartum period). We found an increased, but not significant, risk of a new episode of cerebral ischaemia in patients with pregnancies complicated by preeclampsia (two out of the eight preeclampsia (p 0.15). Despite treatment, there is a significant risk for pregnancy complications in APS patients with previous CVE. Especially in the context of preeclampsia, anticoagulation should be given rigorously to prevent recurrence of CVE.

Relapsing polychondritis in childhood – case report and short review

Abstract Relapsing polychondritis (RP) is a disease of unknown etiology and it is characterized by inflammation of the cartilage. While the clinical picture of RP in adults is well described, RP in childhood is poorly documented. We describe a young girl presenting with acute dyspnea, stridor and polyarthritis. The diagnosis of RP was made 2 years after first presentation, when auricular chondritis occurred. Based on a MEDLINE search, reports on RP in childhood were reviewed. The frequency of chondritis and systemic manifestations of RP in children was compared to data in adults and found to be very similar. RP in childhood can be a life-threatening and debilitating disease.

Krankheitsbezogene Internetnutzung bei Patienten mit entzündlich-rheumatischen Systemerkrankungen

Zusammenfassung.Einleitung:Im Rahmen des Kompetenznetzes entzündlich-rheumatische Systemerkrankungen entsteht erstmalig eine umfassende, überregionale horizontale und vertikale Vernetzung von Forschung und Versorgung auf dem Gebiet der Rheumatologie. Durch die verbesserte Kommunikation und Kooperation soll mittelfristig die Qualität wissenschaftlicher Arbeiten und der Patientenversorgung erhöht werden. Die vorliegende Untersuchung sollte analysieren, in welchem Umfang Patienten bereits das Internet nutzen, welche technischen Voraussetzungen bei den Patienten bestehen, welche Informationsangebote im Internet bereits gesucht bzw. genutzt werden und wo die Themenschwerpunkte der Informationsbedürfnisse liegen.Methodik:Ende 2001 und Anfang 2002 führten wir eine Umfrage unter 400 konsekutiven Patienten der Rheuma-Ambulanz der Heinrich-Heine-Universität Düsseldorf durch. Mittels eines anonymisierten doppelseitigen Fragebogens wurden die Daten zur aktuellen EDV-Ausstattung und Internetnutzung erhoben.Ergebnisse:326 Patienten füllten den Fragebogen aus. 163 der Befragten nutzten regelmäßig das Internet, hierbei insbesondere jüngere Patienten und Patienten mit höherer Schul- bzw. Berufsausbildung. Eine Abhängigkeit von Geschlecht oder Familienstand zeigte sich nicht, Männer gaben aber im Mittel eine längere wöchentliche Nutzungsdauer des Internet an. 55,8% der befragten Internetnutzer benutzten das Medium für gesundheitliche Fragestellungen. Führend bei der Nutzung des Internet für medizinische Belange war bei den Patienten die Suche nach den aktuellen Behandlungsmöglichkeiten (46,6%) und aktuellen Informationen zu den einzelnen spezifischen Krankheitsbildern (28,8%).Schlussfolgerung:Das Internet ist eine wesentliche Informationsquelle für Rheuma-Patienten. Für die Kommunikation über das Internet bestehen bei etwa der Hälfte der Patienten die entsprechenden technischen Voraussetzungen und auch eine hohe Bereitschaft zum Informationsaustausch. Um diesen Anforderungen gerecht zu werden, muss sich die Internetplattform des Kompetenznetzes insbesondere an den Patientenbedürfnissen orientieren und diese auch unter Beibehaltung einer hohen inhaltlichen Qualität erfüllen.Summary.Objective:On behalf of the „systemic inflammatory rheumatic diseases network“ comprehensive, nationwide horizontal and vertical cross-linking of research and care is to be developed for the first time. The quality of scientific work and patient care is to be increased in the medium term through this improved communication and co-operation. Our objective was to determine what hardware and software are available to the patients involved, with a view to the Internet being used as a basis for communication. The ultimate aim was to provide patients with an adequate source of information on care.Methods:A survey was carried out among 400 patients attending our outpatient clinics. Data on the hardware and software used and on Internet access and patterns and degree of utilization were collected using a unilateral questionnaire.Results:326 patients filled in the questionnaire. 163 of those responding had Internet access, with younger and better educated patients using the Internet significantly more frequently. No dependency was noted on gender or marital status. Mean time duration for Internet use was longer in men. 55.8% of the internet users searched for medical questions. Major search topics included up to date therapeutic options (46.6%) and information on specific diseases (28.8%).Conclusion:Internet is an important information medium for patients. Technical requirements and high motivation make communication practicable for about 50% of patients. To ensure acceptance, the Internet platform of the systemic inflammatory rheumatic diseases network needs to be aligned to patients’ requirements, bearing in mind the need for extensive high-value, reliable scientific information to be offered on the website.