The ageing joint-standard age- and sex-related values of bone erosions and osteophytes in the hand joints of healthy individuals.

OBJECTIVE: To analyze the age-related changes of the physiological hand joint architecture. METHOD: To address this concept, healthy individuals (each 10 women and 10 men in six different age decades spanning from 21 to 80 years) were recruited through a field campaign, investigated for the absence of rheumatic diseases and other comorbidities and received high-resolution quantitative computed tomography (HR-pQCT) examination of the hand joints. Number and extent of erosions and osteophytes were quantified across the ages and different sexes. RESULTS: Bone erosions [median (Q1-Q3), 1 (0-2)] and osteophytes [2 (1-4)] were found in healthy women and men with no significant sex differences. Structural changes however accumulated with age: the overall incidence rate ratio (IRR) for the number of erosions and osteophytes per age were 1.04 (95% CI: erosions 1.03-1.06; osteophytes: 1.03-1.05). This means a 4% increase in the number of erosions and osteophytes per year. Using third decade as reference, healthy individuals in the age decades from 50 years had higher IRR for erosion numbers (sixth, seventh, eigth decade: 4.87 (2.20-11.75), 6.81 (3.08-16.46) and 6.92 (3.11-16.79)) compared to younger subjects (fourth, fifth decade: 1.80 (0.69-4.87), 1.53 (0.59-4.10)). The IRRs of osteophytes also indicate a gradual increase after the fifth decade, with IRRs of 2.32 (1.32-4.17), 4.17 (2.38-7.49) and 6.86 (3.97-12.20) for the sixth, seventh and eigth decades, respectively. CONCLUSIONS: Structural changes in the hand joints of healthy individuals are age dependent. While being rare under 50 years of age, erosions and osteophytes accumulate above the age of 50, suggesting that the threshold between "normal" and "pathological" is shifted with the increase of age.

ALIGNed on adherence: subanalysis of adherence in immune-mediated inflammatory diseases in the DACH region of the global ALIGN study.

BACKGROUND: Non-adherence to medication is a challenging problem in daily clinical practice. OBJECTIVE: To assess reasons for non-adherence in patients with chronic immune-mediated inflammatory diseases (IMIDs) in a direct comparison including evaluation of treatment necessity and concerns. METHODS: ALIGN was a non-interventional, multicountry, multicentre, self-administered, cross-sectional, epidemiologic survey study. Here, we investigate the German, Austrian and Swiss (DACH) cohort. Six hundred thirty-one patients with different IMIDs (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, Crohn's disease and ulcerative colitis) under systemic therapies were evaluated concerning adherence, beliefs of necessity and concerns towards treatment in patients with IMIDs. RESULTS: The DACH cohort had significantly different levels of adherence depending on the IMID (P < 0.05) and the type of therapy (P < 0.05). Based on the significant influence of concerns on treatment adherence (P < 0.05) and the high belief of treatment necessity, patients could be classified in four attitudinal segments, which were unequally distributed throughout various IMIDs. High concerns had a significant influence on non-adherence, whereas necessity did not. Older age, female sex, TNFi mono-, conventional combination and TNFi combination therapy are positively associated with adherence. CONCLUSIONS: In the DACH region, patients are less concerned about medication and believe in the necessity of treatment. Therefore, we suggest adapting the communication in the various patient groups.

[Use of medical apps and online platforms among German rheumatologists : Results of the 2016 and 2018 DGRh conference surveys and research conducted by rheumadocs]. / Nutzung von Medizin-Apps und Online-Plattformen unter deutschen Rheumatologen : Ergebnisse der rheumadocs-Recherche und DGRh-Kongress-Umfragen von 2016 und 2018.

BACKGROUND: Apps and online platforms play an ever increasing role in the daily work routine of physicians. The aim of this study was to investigate which medical apps and online platforms are used by German rheumatologists for certain tasks and to identify usage trends. METHODS: Data were collected via a SurveyMonkey survey conducted by members of rheumadocs (Young German Rheumatology Association) at the 2016 and 2018 German Society for Rheumatology (DGRh) conferences. RESULTS: In 2016 and 2018 the survey was completed by 75 and 84 assistant and specialist rheumatologists, respectively. In 2016, 37% of rheumatologists were using medical apps in routine care which changed to 49% in 2018. In 2016, 47% compared to 68% in 2018, planned to integrate medical apps into routine care. In total, 20 different medical apps were recommended for colleagues to use; however only 2 of these apps were specific for rheumatology. In contrast to 52 app recommendations for colleagues, only 8 app recommendations for patients were recorded. Most recommendations to physicians received the app "Arznei aktuell" (21%). "Embryotox" was the app, most recommended to patients (38%). In 2016 the online database PubMed was most popular and 97% of participants were familiar with it. Use of other online platforms showed great age dependency in 2016: Amboss (a digital learning platform) was used by 31% of the age group 21-30 years and was not used at all by the age group 51-60 years. DISCUSSION: Use of medical apps and planned integration of medical apps into routine care is increasing among German rheumatologists. On the other hand, recommendable rheumatological apps for rheumatologists and especially for patients are currently largely unknown to rheumatologists.

[Novel molecular mechanisms in the pathophysiology of psoriatic arthritis]. / Neue molekulare Mechanismen in der Pathophysiologie der Psoriasisarthritis.

The complex pathogenesis of psoriatic arthritis (PsA) is still only partially understood; however, recently a greatly improved understanding of this disease has been achieved, especially with respect to the inflammatory processes of the entheses. Thus, the clinical aspects of enthesitis increasingly differentiate PsA from other autoimmune diseases and sharpen the unique pathological clinical picture of PsA. Better pathophysiological understanding and the development of different biomarker approaches will bolster early detection of PsA. Therefore, the successful early recognition of PsA and more reliable identification of psoriasis patients at risk might be possible in the near future.

No evidence of pathogenic involvement of cathelicidins in patient cohorts and mouse models of lupus and arthritis.

Apart from their role in the immune defence against pathogens evidence of a role of antimicrobial peptides (AMPs) in autoimmune diseases has accumulated in the past years. The aim of this project was to examine the functional impact of the human cathelicidin LL-37 and the mouse cathelicidin-related AMP (CRAMP) on the pathogenesis of lupus and arthritis. Serum LL-37 and anti-LL-37 levels were measured by ELISA in healthy donors and patients with Systemic Lupus Erythematosus (SLE) and Rheumatoid arthritis (RA). Pristane-induced lupus was induced in female wild type (WT) and cathelicidin-deficient (CRAMP-/-) mice. Serum levels of anti-Sm/RNP, anti-dsDNA, and anti-histone were determined via ELISA, cytokines in sera and peritoneal lavages were measured via Multiplex. Expression of Interferon I stimulated genes (ISG) was determined by real-time PCR. Collagen-induced arthritis (CIA) was induced in male WT and CRAMP-/- mice and arthritis severity was visually scored and analysed histomorphometrically by OsteoMeasure software. Serum levels of anti-LL-37 were higher in SLE-patients compared to healthy donors or patients with RA. However, no correlation to markers of disease activity or organ involvement was observed. No significant differences of autoantibody or cytokine/chemokine levels, or of expression of ISGs were observed between WT and CRAMP-/- mice after pristane-injection. Furthermore, lung and kidney pathology did not differ in the absence of CRAMP. Incidence and severity of CIA and histological parameters (inflammation, cartilage degradation, and bone erosion) were not different in WT and CRAMP-/- mice. Although cathelicidins are upregulated in mouse models of lupus and arthritis, cathelicidin-deficiency did not persistently affect the diseases. Also in patients with SLE, autoantibodies against cathelicidins did not correlate with disease manifestation. Reactivity against cathelicidins in lupus and arthritis could thus be an epiphenomenon caused by extensive overexpression in blood and affected tissues. In addition, other cationic AMPs could functionally compensate for the deficiency of cathelicidins.

[New aspects on the pathogenesis of psoriatic arthritis]. / Neues zur Pathogenese der Psoriasisarthritis.

Psoriasis and psoriatic arthritis (PsA) are immune-mediated inflammatory diseases with a high burden of disability and increased mortality. The pathogenesis of the disease comprises a dysregulated interaction between stromal and immune cells and a dysfunctional cytokine network supporting chronic inflammation of the skin, entheses and joints. In addition to recent advances in the understanding of TNF blockade, more targets have been discovered delivering insights into the pathogenesis of PsA. This article gives a translational approach by utilizing current clinical development programs providing an insight into the IL-12/IL-23 and the IL-17 axes and also focuses on tissue damage and new small molecules.

Adaptation and cross-cultural validation of the rheumatoid arthritis work instability scale (RA-WIS).

BACKGROUND: Despite recent advances, work disability in rheumatoid arthritis (RA) remains common. Work disability is frequently preceded by a period of work instability characterised by a mismatch between an individual's functional abilities and job demands. This could raise the risk of work disability if not resolved. A work instability scale for RA (RA-WIS) has previously been developed to screen for this risk. The objective of this study was the adaptation of this scale into French, Dutch and German. METHOD: Different language versions of the RA-WIS were produced through a process of forward and back translations. The new scales were tested for face validity. English data from the original developmental study was pooled with data generated through postal surveys in each country. The internal construct and cross-cultural validity of the new scales were assessed using Rasch analysis, including differential item functioning (DIF) by culture. RESULTS: The pooled data showed good fit to the Rasch model and demonstrated strict unidimensionality. DIF was found to be present for six items, but these appeared both to cancel out at the test level and have only a marginal effect on the test score itself. CONCLUSIONS: The RA-WIS was shown to be robust to adaptation into different languages. Data fitted Rasch model expectations and strict tests of unidimensionality. This project and the continuing work on further cross-cultural adaptations have the potential to help ensure clinicians across Europe are able to support RA patients to achieve their potential in work through early identification of those most at risk.

Bypassing non-adherence via PEG in a critically ill HIV-1-infected patient.

This case study describes a 44-year-old, chronically non-adherent, HIV-infected male with relapsing, life threatening toxoplasmic encephalitis (TE) and other recurring opportunistic infections. Non-adherence resulted in critical illness, suppressed CD4 lymphocyte count and elevated viral load. In order to bypass the patient's complete psychological aversion to taking medication, and after exhausting various psychological interventions, a percutaneous endoscopic gastronomy (PEG) tube was inserted for delivery of indispensable medication. During the 15-month follow-up the patient was adherent, exhibiting a consistently undetectable viral load, high CD4 count and a remission of the opportunistic infections. This is an interesting case study demonstrating life-saving and long-term benefit of PEG in an exceptional setting, which has implications for future research and treatment of non-adherent HIV-infected patients.

Plasmapheresis therapy in an elderly patient with rapidly progressive Henoch-Schönlein purpura with disseminated organ involvement.

Henoch-Schönlein purpura (HSP) frequently occurs in children below the age of 15 years and is rare with increasing age. Prognosis and therapy largely depend on the clinical presentation. The disease may be preceded by an upper respiratory tract infection, and drugs have also been implicated in the pathogenesis of the disease. Most children recover from the illness, whereas 40% of adults have persistent hematuria and 10% develop chronic renal failure. Recent studies strongly suggest that adults with HSP should be monitored for prolonged periods and treated aggressively. Here, we present a case of a patient with HSP who developed multiorgan failure requiring assistance in breathing and dialysis, and also sustained gastrointestinal bleeding despite aggressive immunosuppressive therapy. In analogy to published data in children with severe HSP, the patient was treated by plasma exchange in combination with low dose oral cyclophosphamide, while high dose steroids were reduced over time. The patient could be discharged 70 days after admission. One year after discharge, the patient is doing well without any signs of activity of HSP and completely unremarkable renal function. The maintenance daily dose of steroids is 7.5 mg.

[Superior vena cava syndrome: Catheter association as a rare cause]. / Vena-cava-superior-Syndrom: Katheterassoziation als seltene Ursache.

HISTORY AND FINDINGS: A 78 year-old-woman was admitted with a swollen face, edema of the lower eyelids and dyspnea. The past medical history revealed an ovarian carcinoma treated with polychemotherapy. Half a year before the patient had been investigated for similar clinical symptoms but no underlying cause had been detected. The histology of an enlarged axillary lymph node did not show a malignancy. The symptoms persisted after angioedema-inducing drugs had been discontinued. INVESTIGATIONS: Initial CT scan, magnetic-resonance tomography as well as positron emission tomography failed to explain the clinical findings. Also, testing of serological, immunological and endocrinological tests as well as the differential blood count did not reveal a likely cause of the clinical symptoms. However, 4 weeks later, a repeat CT scan showed a stenosis of the superior vena cava (SVC) establishing the diagnosis of an SVC syndrome. TREATMENT AND COURSE: The port catheter tipp was localized horizontal to the vena cava superior and was touching the vein wall. Removal of the catheter and subsequent balloon dilatation of the stenosis immediately lead to a reduction of the eyelid swelling. CONCLUSIONS: Hence, in a case of an SVC-syndrome, complete stenosis caused by an implanted venous access system should be considered though it is rare.

Paraneoplastic syndrome, infection or arthritis: Difficulties in diagnosis.

Many different diseases have overlapping clinical symptoms. A major challenge in daily clinical practice is to differentiate between diseases associated with systemic inflammation, such as neoplasia, infection and autoimmune disease. We report on a 46-year-old Caucasian male with a 3-month history of rheumatoid arthritis presenting with dramatic weight loss and dysphagia. Computer tomography revealed multiple lesions in the liver and the spleen, strongly suggesting malignant disease of unknown origin. Surprisingly, on biopsy, the liver lesions drained pus. Workup revealed that the abscesses resulted from gastric perforation, which was the consequence of NSAR therapy for rheumatoid arthritis. Antibiotic therapy was initiated, abscesses diminished and dysfunctional deglutition improved. This unique case demonstrates in a dramatic way the difficulties in daily clinical practice to differentiate between paraneoplasia, infection and autoimmune disease and the potentially life-threatening consequences of their therapy.

The release of microparticles by apoptotic cells and their effects on macrophages.

Microparticles are small membrane vesicles released from the cell membrane by exogenous budding. To elucidate the interactions of microparticles with macrophages, the effect of microparticles released from Jurkat T cells on RAW 264.7 cells was determined. Microparticles were isolated by differential centrifugation, using FACS analysis with annexin V and cell surface markers for identification. Various inducers of apoptosis increased the release of microparticles from Jurkat cells up to 5-fold. The released microparticles were then cultured with RAW 264.7 cells. As shown by confocal microscopy and FACS analysis, RAW 264.7 macrophages cleared microparticles by phagocytosis. In addition, microparticles induced apoptosis in RAW 264.7 cells in a dose-dependent manner with up to a 5-fold increase of annexin V positive cells and 9-fold increase in caspase 3 activity. Cell proliferation as determined by the MTT test was also reduced. Furthermore, microparticles stimulated the release of microparticles from macrophages. These effects were specific for macrophages, since no apoptosis was observed in NIH 3T3 and L929 cells. These findings indicate that microparticles can induce macrophages to undergo apoptosis, in turn resulting in a further increase of microparticles. The release of microparticles from apoptotic cells may therefore represent a novel amplification loop of cell death.