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Despite a qualitatively and structurally good care of patients with rheumatoid arthritis (RA) in Germany, there are still potentially amendable deficits in the quality of care. For this reason, the German Society for Rheumatology (DGRh) has therefore decided to ask a group of experts including various stakeholders to develop quality standards (QS) for the care of patients with RA in order to improve the quality of care. The QS are used to determine and quantitatively measure the quality of care, subject to relevance and feasibility. The recently published NICE and ASAS standards and a systematic literature search were used as the basis for development. A total of 8 QS, now published for the first time, were approved with the intention to measure and further optimize the quality of care for patients with RA in Germany.Trotz einer qualitativ und strukturell guten Versorgung von Patient*innen mit rheumatoider Arthritis (RA) in Deutschland bestehen weiterhin potenziell behebbare Defizite in der Qualität der Versorgung. Aus diesem Grund hat die Deutsche Gesellschaft für Rheumatologie (DGRh) eine Expert*innengruppe, in der verschiedene Interessengruppen vertreten waren, beauftragt, nationale Qualitätsstandards (QS) mit dem Ziel zu entwickeln, die rheumatologische Versorgung von Patient*innen mit RA in Deutschland qualitativ zu verbessern. QS dienen der Festlegung und quantitativen Messung guter Versorgungsqualität unter dem Vorbehalt von Relevanz und Realisierbarkeit. Als Grundlage für die Entwicklung dienten die kürzlich publizierten Standards von NICE und ASAS und eine systematische Literatursuche. Insgesamt wurden 8 hiermit erstmals veröffentlichte QS konsentiert, die als Grundlage dienen können, die Versorgungsqualität von Patient*innen mit RA in Deutschland zu messen und weiter zu optimieren.

BackgroundGiant cell arteritis (GCA) has the tendency to relapse once treatment is tapered or stopped. Such relapses represent a potential threat to GCA patients as they can lead to severe symptoms and organ damage.ObjectivesTo assess the frequency and type of relapses in patients with GCAMethodsThe Real-Life Treatment and Safety (REATS)-GCA cohort has been established by extracting the data on clinical presentation, inflammatory markers, imaging, comorbidities, treatments and serious adverse events of GCA patients from 6 specialized centres in Germany. We undertook descriptive and survival analyses (Kaplan-Meier), and compared baseline characteristics of participants with vs. without relapse. Ethical approval for the cohort was obtained.ResultsWe included 395 patients with a mean age of 71 years, including 264 (66.8 %) females and 129 (32.7%) males. Diagnosis of GCA was supported by temporal artery ultrasound in 37%, 18F-FDG-PET/CT in 29%, temporal artery biopsy in 14% of patients and by MRI or clinically in the remaining patients. 31% of patients presented with an isolated cranial manifestation and 18% with isolated extracranial manifestations. Most common presenting symptoms were headache (57%), fatigue (55%), weight loss (42%) and polymyalgia (38%) (Table 1). The most common comorbidities at the time of study inclusion were arterial hypertension (68%), followed by osteoporosis (26%). Within a median total follow-up duration of 22.2 (11.7-40.6) months, 97 of the 395 patients relapsed including 15 patients who relapsed more than once. The median (IQR) time to first relapse was 12.5 (7.1-21.8) months. Median relapse-free survival was 7.8 years with a relapse risk of 12% (CI, 9 to 15%) at 1 year and 38% (CI, 30 to 45%) at 5 years (Figure 1). Most common symptoms at relapse were headache (35%), polymyalgia (23%), fatigue (19%) and night sweats (12%) (Table 1). Three patients relapsed with sudden loss of vision. Among the 114 relapses observed, 94 (83%) occurred under prednisolone treatment with a median dose of 7.0 mg/day (IQR 4.0-12.5). 26 (23%) occurred under methotrexate and 14 (12%) under tocilizumab treatment. Comparing the baseline characteristics that were documented in this study, we did not find a statistically significant difference in relapsing versus non-relapsing GCA patients.Table 1.Symptom at disease onsetN=395 (%)Symptom at relapseN=97 (%)Headache216 (54.7)Headache35 (30.7)Fatigue208 (52.7)Polymyalgia (PMR)23 (20.2)Weight loss159 (40.3)Fatigue19 (16.7)Polymyalgia (PMR)144 (36.5)Vision impairment13 (11.4)Night sweats140 (35.4)Night sweats12 (10.5)Headache in the temple area125 (31.6)Headache in the temple area12 (10.5)Jaw pain121 (30.6)Jaw pain11 (9.6)Vision impairment118 (29.9)Morning stiffness7 (6.1)Morning stiffness89 (22.5)Weight loss7 (6.1)Fever80 (20.3)Claudication upper limb6 (5.3)Swelling temporal arteries77 (19.5)Arthralgia6 (5.3)Vision loss57 (14.4)Claudication lower limb5 (4.4)Scalp tenderness38 (9.6)Vision loss3 (2.6)Claudication upper limb38 (9.6)Arthritis3 (2.6)Claudication lower limb34 (8.6)Scalp tenderness2 (1.8)Arthralgia28 (7.1)Fever2 (1.8)Arthritis3 (0.8)Swelling temporal arteries2 (1.8)Figure 1.ConclusionAbout one fourth of GCA patients relapsed and the overwhelming majority of relapses occurred before patients were able to stop glucocorticoids. The leading symptoms at relapse are headache and fatigue, while loss of vision is rare (0.76%). Baseline characteristics seem to be poorly informative about the risk of relapse, therefore regular monitoring of GCA patients is necessary.AcknowledgementsThis research was financially supported by Roche Pharma Ag and Chugai Pharma Europe Ltd.Disclosure of InterestsVerena Schönau Speakers bureau: Novartis, Janssen, Grant/research support from: Roche, Chugai, Giulia Corte: None declared, Sebastian Ott: None declared, Koray Tascilar: None declared, Fabian Hartmann: None declared, Bernhard Manger: None declared, Bernhard Hellmich: None declared, Alexander Pfeil: None declared, Peter Oelzner: None declared, Wolfgang A. Schmidt: None declared, Andreas Krause: None declared, Marc Schmalzing: None declared, Matthias Fröhlich: None declared, Michael Gernert: None declared, Nils Venhoff: None declared, Jörg Henes: None declared, Jürgen Rech Speakers bureau: Abbvie, Biogen, BMS, Chugai, GSK, Lilly, MSD; Novartis, Roche, Sanofi, Sobi, UCB,, Consultant of: Biogen, BMS, Chugai, GSK, Lilly, MSD, Novartis, Roche, Sanofi, Sobi, UCB, Grant/research support from: Sobi, Novartis, Georg Schett: None declared

BackgroundThe first vaccine against SARS-CoV-2 was approved in December 2020. Immunogenicity of SARS-CoV2 vaccines in patients with immune-mediated inflammatory disease (IMID) have so far been evaluated in the 2-6 weeks following complete vaccination and risk groups for poor early vaccine response have been identified leading to specific vaccination recommendations. However, data on the long-term course and persistence of vaccine response in IMID patients, as well as the outcomes of the specific recommendations are lacking.ObjectivesTo evaluate the long-term course of humoral response to SARS-CoV-2 vaccination in a large prospective cohort of IMID patients and non-IMID controls with a follow-up duration of up-to to 10 months after the first vaccine dose.MethodsWe have initiated a prospective dynamic cohort of IMID patients and healthy controls in February 2020 to monitor immune response to SARS-CoV-2 and respiratory infections including COVID-19 (1). Participants who contributed data starting from the 4 weeks before their first vaccination onwards were included in this analysis. Antibodies against SARS-CoV-2 spike protein were quantified with an ELISA from Euroimmun (Lübeck, Germany) with an optical density cutoff of 0.8. We fitted linear mixed-effect models for log-transformed antibody levels using time splines with adjustment for age and sex. Marginal mean antibody levels with 95% confidence intervals (CI) were estimated at selected time points for IMID patients and controls with double vaccination. We descriptively analyzed the observed antibody levels over time in cohort participants receiving two vaccinations vs. three vaccinations.ResultsAmong 5076 cohort participants, 3147 IMID patients and healthy controls (mean (SD) age 49 (16)) provided 4756 samples for this analysis between December 2020 and 2021, with a median (IQR) 28 (14-31) weeks of follow-up after the first vaccination (Table 1). 2965 (94%) participants had received at least 2 and 223 (7%) participants had received three vaccine doses by the date of their latest sampling. In IMID patients, age and sex-adjusted estimated marginal mean antibody levels waned after week 16 and were substantially reduced at all time points compared to the controls, finally dropping to the borderline range (1.01, 95%CI 0.86 to 1.19) at week 40 (Figure 1A, Table 1). A third dose was given to 128 (7%) of IMID patients with a poor response to 2 vaccine doses after a median 20 weeks of the second dose (IQR 10 to 26 weeks). After the third dose, antibody levels in IMID patients were comparable to those of healthy controls at 40 weeks who had three vaccine doses. These were also higher than that of IMID patients and controls who did not receive a third dose (Figure 1B).Table 1.Participant characteristics and antibody levelsHealthy controlsIMID N11991948 Age, mean (SD)40.8 (13.5)54.3 (14.8) Follow-up, weeks, median (IQR)31.1 (23.8-36.6)19.6 (12.3-26.6) Follow-up range, weeks,1.6-46.11.7-46.3Sex, n(%) Female554 (46.2)1136 (58.3)Vaccine intervals, ´median (IQR) 1st to 2nd dose4.6 (3.0-6.0)6.0 (5.0-6.1) 2nd to 3rd dose29.6 (26.9-36.4)19.9 (10.0-26.1)Diagnosis, n (%) Spondyloarthritis-713 (36.6) Rheumatoid arthritis-489 (25.1) Autoimmune disease, systemic+-420 (21.5) Inflammatory bowel disease-219 (11.2) Psoriasis-107 (5.5)Mean* antibody levels after 1st dose Week-84.16 (3.89 to 4.45)2.97 (2.83 to 3.12) Week-168.39 (7.81 to 9.02)5.04 (4.81 to 5.28) Week-325.02 (4.73 to 5.33)2.52 (2.32 to 2.74) Week-402.14 (1.95 to 2.35)1.01 (0.86 to 1.19)+ Systemic lupus, systemic sclerosis, Sjögren’s syndrome, vasculitis* Estimated marginal means adjusted for age and sex.Figure 1.ConclusionHumoral response to vaccination against SARS-CoV-2 was weaker in IMID patients compared to controls at all time points after the first vaccine dose and practically disappeared after 1 year. IMID patients can still achieve a good antibody response with a third dose even after a weak response with two doses.References[1]Simon D et al Nat Commun 2020Disclosure of InterestsNone declared

Calcification in hyaline and fibrocartilage is caused by the deposition of calcium pyrophosphate dehydrate, commonly referred to as chondrocalcinosis. Clinically, this can lead to arthritis symptoms similar to a gout attack -"pseudogout". Nonetheless, also chronic or asymptomatic disease courses are possible. The prevalence of chondrocalcinosis increases with age. The diagnostic workup of degenerative joint disease, therefore, often reveals calcifications of articular cartilage as harmless incidental findings. However, particularly in patients younger than 60 years of age, chondrocalcinosis can be the symptom of an underlying metabolic disease. This review article highlights these rare diseases and presents unusual manifestations of chondrocalcinosis.

Depressive disorders are among the most common comorbidities in patients not only with rheumatoid arthritis (RA) but also with other forms of inflammatory rheumatic diseases. The prevalence of a depressive disorder in RA is estimated to be between 9.5% and 41.5% depending on the study and with women being more affected. After adjusting for sex, age and other parameters the risk of depression in RA was significantly elevated with an odds ratio of 1.63 (95% CI, 1.43-1.87) compared to the general population. In RA the risk of developing a depressive disorder is highest in the first 5 years and depression is a better predictor of work disability than disease activity and response to treatment. Depression in RA is associated with more pain, fatigue and impaired quality of life, whereby the association between depression and RA is bidirectional. Therefore, the risk to develop a depression is increased with impaired function as measured by the health assessment questionnaire (HAQ) and there is evidence that increased disease activity increases the risk for depression in RA. In addition, a depressive disorder also affects the subjective severity of patient-reported outcomes (PRO), such as tender joints and the global patient assessment with respect to disease activity and thus exhibiting a direct influence on the DAS28. Finally, it could be shown that depression unfavorably influences the response to therapy, the rate of remission is lower and the mortality is increased in RA patients. Taken together, this indicates that it is necessary to detect a depression in patients with RA as early as possible in order to initiate appropriate treatment of depression in such cases.

During the last 3 years 4 patients were admitted to this hospital with a wide variety of different symptoms, in whom Erdheim-Chester disease (ECD) was diagnosed via different diagnostic pathways.Based on four clinical cases of ECD and using additional information from the literature, this article presents the symptoms of ECD. Furthermore, similarities and differences in comparison to important rheumatological differential diagnoses are presented.The ECD is a multi-organ orphan disease. Typical for the disease are long bone involvement, periarterial inflammation especially of the aorta, retroperitoneal and perirenal fibrosis with so-called hairy kidneys in abdominal computed tomography (CT) scans. Treatment is increasingly directed towards the presence of a BRAF mutation, which enables targeted and effective treatment with BRAF inhibitors.The ECD is a rare differential diagnosis to rheumatic diseases that causes various and often nonspecific symptoms. Due to modern diagnostic methods with imaging procedures and biopsies it is possible to establish a precise diagnosis and provide a targeted and effective treatment.

Background Heart failure (HF) is a condition with high rates of hospital admission and mortality. The impact of rheumatoid arthritis (RA) and its treatment on the prognosis of prevalent HF has been insufficiently studied. Objectives To evaluate deterioration of HF and mortality in patients with RA and concomitant HF. Methods The prospectively followed cohort of the German register RABBIT continuously includes RA patients with a new start of a DMARD after at least one csDMARD failure. Among all patients enrolled between 05/2001 and 10/2017 (n=15,037) patients with prevalent HF were selected (n=393). HF patients were followed until their end of observation or death. Deterioration of HF requiring hospital admission, and death were analysed as composite outcome. Incidence rates (IR) were calculated for current treatment at time of event (9 months risk window after last infusion of rituximab). Generalised estimation equations (GEE) were used to investigate risk factors for the composite outcome. To avoid uncertainties when allocating therapies, only treatment episodes>6 months were included in the GEE analysis. Missing values (DAS28, CRP, physical function) were addressed by multiple imputations. Results Of the 393 patients with prevalent HF and 1490 patient years (PY) of follow-up, a total of 131 patients had at least one outcome (19 HF deteriorations, 123 deaths). Infections (30%) and cardiovascular events (25%) were most frequently reported as causes of death. The mean time until deterioration/death was 30/35 months. At baseline, patients with an event were older (69 vs. 67 years), more often male (43 vs. 32%), rheumatoid factor positive (80 vs. 74%), had higher CRP-values (39 vs. 23 mg/L) and a worse FFbH (% of physical function: 43 vs. 50) than patients without event. All HF patients had high numbers of comorbidities (mean of 7/6 in patients with/without event). Crude IR were highest in patients under csDMARD only exposure (figure 1). IR were similar during the first 3 or 6 months after start of treatment and thereafter (data not shown). Biologic treatment was not associated with the outcome (table 1). Male gender, higher age, a higher glucocorticoid dose, worse physical function and elevated CRP under treatment were significantly associated with hospitalisation due to HF or a fatal outcome. Conclusions Patients with RA and HF have an unfavourable prognosis. One third of them were hospitalised for HF or died during follow-up. In addition to patient characteristics, smoking, insufficiently controlled inflammation and treatment with glucocorticoids significantly increased the risk of hospitalisation or death. Acknowledgements RABBIT is supported by a joint, unconditional grant from AbbVie, Bristol-Myers Squibb, Celltrion, Hexal, Lilly, MSD Sharp and Dohme, Pfizer, Roche, Samsung Bioepis, Sanofi-Aventis und UCB. Disclosure of Interest Y. Meissner Speakers bureau: Pfizer, M. Schafer: None declared, B. Manger: None declared, M. Zanker Speakers bureau: Celgene, MSD, Roche, W. Ochs: None declared, J. Listing: None declared, A. Strangfeld Speakers bureau: AbbVie, BMS, Lilly, MSD, Pfizer, Roche, UCB

Hintergrund Im Dezember 2014 stellte sich in unserer Klinik ein Patient mit dem klinischen Bild einer Vaskulitis vor. Unter Glukokortikoiden kam es jedoch zu keiner Besserung, sodass differenzialdiagnostisch andere Ursachen einbezogen wurden und schlieslich Skorbut diagnostiziert wurde.

Background Psoriatic skin disease is a burdensome, sometimes painful, dermatologic condition which was reported to occur as an adverse event (AE) during TNF-inhibitor (TNFi) treatment of rheumatoid arthritis (RA). Single case reports revealed the occurrence of psoriasis also during treatment with non-TNFi, but the magnitude under those agents remains unclear. Objectives To compare incidence rates of psoriasis in RA under treatment with different biologic and conventional synthetic (b/cs)DMARDs and to investigate risk factors. Methods We used data of 12,722 patients (53,585 patient years (py)) enrolled with the start of a b/csDMARD in the German biologics register RABBIT. Patients were required to have no psoriasis at baseline and at least one follow-up. All psoriatic events (PsE) reported until 30 April 2016 were selected and assigned to treatments administered within 3 months prior to the event. Crude incidence rates (IR) of PsE were calculated per 1,000py. Cox regression was applied to investigate risk factors for the occurrence of PsE with and without inverse probability weights (IPW) to adjust for confounding by indication. Results 96 PsE were reported, with only 6 of them categorized as being serious. The median time between enrollment in the cohort and onset of psoriasis was 19 months (IQR:11–45 months). 21 of all PsE (22%) were palmoplantar manifestations of which 9 were reported as pustular type. Compared to csDMARD treatment with a crude IR of 0.44/1,000py (95% CI 0.2;0.9), the IRs found under TNFi (IR 2.99 (95% CI 2.3;3.8)) and abatacept (IR 3.99 (95% CI 1.7;7.9)) were significantly higher. In patients treated with rituximab (IR 1.8 (95% CI 0.8;3.4)) or tocilizumab (IR 0.7 (95% CI 0.1; 2.0)) IRs for PsE were not significantly different from csDMARD patients. Across TNFi, the IR varied insignificantly. Adjusted regression analysis showed higher risk for PsE with TNFi, abatacept and rituximab (graph). Female sex (adjusted hazard ratio (HR) 1.8 (1.0;3.3)) and being rheumatoid factor negative (HR 1.6 (1.0;2.6)) were additional significant risk factors. Smoking (HR 1.6 (1.0; 2.5)), age (HR 1.0 (0.98;1.01)), glucocorticoids per 5 mg/d increase (HR 1.1 (1.0;1.2)), and prior (≤6months) skin infections (HR 2.2 (0.5;9.7)) were not significantly associated. Replacing glucocorticoids with DAS28 did not show differing results. Adjustment with IPW attenuated the effect of rheumatoid factor (p=0.4) but smoking was significantly associated with a higher risk (p Conclusions This is the first analysis comparing the incidence of psoriasis under biologics with different modes of action within one cohort. Our results confirmed a higher risk for TNFi 1 and showed a similar result for abatacept. A lower but still significant increased risk was found for rituximab, whereas there was no difference for tocilizumab compared to csDMARDs. New onset psoriasis is a rare and most often non-serious event. The number needed to harm is 334 patients treated with TNFi for one year to observe one PsE. Acknowledgements RABBIT is supported by a joint, unconditional grant from AbbVie, BMS, Celltrion, MSD, Pfizer, Roche, Samsung and UCB. References Hernandez et al., Arthritis Care Res 2013; 65:2024–31. Disclosure of Interest A. Strangfeld Speakers bureau: BMS, MSD, Pfizer, Roche, Sanofi-Aventis, L. Baganz: None declared, A. Richter Consultant for: Pfizer, B. Manger Consultant for: Abbvie, BMS, MSD, Pfizer, Roche, UCB, G.-R. Burmester Consultant for: AbbVie, BMS, MSD, Pfizer, Roche, UCB, C. Eisterhues: None declared, S. Wassenberg Consultant for: AbbVie, Pfizer, Novartis, Janssen, Roche-Chugai, Celltrion, BMS, Fuji, Speakers bureau: AbbVie, Celgene, Novartis, Pfizer, MSD, Lilly, Janssen, UCB, A. Zink Speakers bureau: AbbVie, BMS, MSD, Pfizer, Roche, UCB, J. Listing Consultant for: Sandoz, Pfizer

Hintergrund: Die Behandlung von Schmerzen im Rahmen einer entzundlichen Gelenkerkrankung (EGE) ist fur die Aufrechterhaltung der Gelenkfunktion und fur die Lebensqualitat der betroffenen Patienten von groser Bedeutung. Die Schmerztherapie ist neben einer immunmodulierenden Basistherapie und dem Einsatz von Glukokortikoiden fur die Unterdruckung der Entzundungsaktivitat ein wesentlicher Baustein in der Behandlung der EGE. Ziel dieser 3e (evidence, expertise, exchange) Initiative war die Entwicklung evidenzbasierter Empfehlungen fur die medikamentose Schmerztherapie der EGE. Material und Methoden: An der internationalen 3e Initiative nahmen 453 Rheumatologen aus 17 Landern teil. Die deutsche Expertenrunde ­bestand aus 66 Teilnehmern. In 3 Diskussionsrunden mit Delphi-Abstimmungen wurden 10 internationale und 2 nationale klinische Fragestellungen hinsichtlich der medikamentosen Schmerztherapie bei EGE ausgewahlt. Anhand einer im Mai 2010 durchgefuhrten systematischen Literaturrecherche (SLR) in Medline, EMBASE, Cochrane Library und den ACR/EULAR Abstracts von 2008/2009 wurden nationale Empfehlungen zusammengestellt und der Zustimmungsgrad der Teilnehmer sowie der Einfluss der Empfehlungen auf ihren klinischen Alltag erfasst. Abschliesend wurden im Plenum aller nationalen Experten die Empfehlungen formuliert. Ergebnisse: Die SLR ergab 49 242 Publika­tionen, von denen 167 fur eine systematische Auswertung geeignet waren. Hieraus wurden 12 Empfehlungen und ein Algorithmus zu den internationalen Fragestellungen fur die medikamentose Schmerztherapie entwickelt. Die Empfehlungen betreffen Wirksamkeit und Sicherheit verschiedener Analgetika, ihren Einsatz bei verschiedenen Begleiterkrankungen sowie wahrend der Schwangerschaft und Stillzeit, die Auswahl von Messinstrumenten fur die Erfassung der Schmerzintensitat und das Schmerzmanagement. Fur die zusatzlichen nationalen Fragestellungen wurden unter 7 334 Arbeiten 34 Publikationen identifiziert, die als Grundlage fur Empfehlungen zur Uberwachung unter Analgetika-Therapie und zum Einsatz pflanzlicher Praparate dienten. Schlussfolgerung: Es wurden insgesamt 14 evidenzbasierte Empfehlungen und ein Algorithmus zur medikamentosen Schmerztherapie der entzundlichen Gelenkerkrankungen entwickelt.

Psoriasis und Psoriasisarthritis (PsA) sind chronisch entzundliche immunvermittelte Erkrankungen mit erheblicher Funktionseinschrankung und erhohter Mortalitat. Pathophysiologisch zeigt sich eine Storung im Zusammenspiel zwischen Gewebe- und Immunzellen als auch des Zytokinnetzwerks und somit eine chronische Entzundung der Haut, Enthesen und Gelenke. Das Verstandnis von immunologischen Vorgangen und einiger Schlusselmolekule wie TNF-α, IL-12/IL-23 und der IL-17-Achse bilden die Grundlage fur mogliche, Erfolg versprechende antirheumatische Therapien. Dieser kurze Uberblick soll auch anhand neuer, sich in Studien befindender Zielmolekule einen Einblick in das Verstandnis der Pathogenese der PsA geben.

Die IgG4-assoziierte Erkrankung ist eine systemische fibroinflammatorische Erkrankung unbekannter Ursache, die mit entzundlichen Schwellungen und Raumforderungen in einem oder mehreren Organen einhergeht. Sie vereinigt zuvor als voneinander unabhangig angesehene Erkrankungen zu einer gemeinsamen Entitat. Kurzlich wurden diagnostische Kriterien fur die Erkrankung und ein internationaler Konsens zur histopathologischen Beurteilung formuliert. Therapeutisch besteht in der Regel ein sehr gutes Ansprechen auf hoher dosiertes Prednisolon (0,6 mg/kg). Unter Dosisreduktion kommt es jedoch haufig lokoregionar oder anderenorts zu Rezidiven. Ubliche steroidsparende Wirkstoffe sind nur teilweise effektiv. Durch anhaltende lokale Entzundungsaktivitat kann es zu Organdestruktionen kommen. Bei refraktaren Verlaufen wurde mit gutem Erfolg Rituximab eingesetzt. In der Langzeitbetreuung der Patienten ist ein wahrscheinlich erhohtes Malignomrisiko (Lymphome, solide Tumoren) zu beachten.

Due to the increasing prevalence of gout, particularly in old age, the disease is becoming of increasing importance in Germany. Gout is one of the most common forms of recurrent inflammatory arthritis and is induced by the deposition of monosodium urate crystals in synovial fluid and other tissues. The principal goals of therapy in chronic gout are the symptomatic treatment of the acute joint inflammation and the causal treatment of the underlying metabolic cause, the hyperuricemia. Only a consistent and permanent reduction of the serum uric acid level ultimately results in an efficient avoidance of further gout attacks and therefore the prevention of structural damage. Due to an often inadequate treatment of gout, the target of healing the disease is often not achieved. A correct and timely diagnosis and adequate assessment of comorbidities associated with gout are, however, of substantial importance for patient and physician to achieve remission of the disease. In order to create a solid basis for a timely and effective treatment of affected patients, in 2016 the German Society of Rheumatology (DGRh) initiated the development of S2e guidelines on gouty arthritis for specialists. This article summarizes these S2e guidelines on the management of gouty arthritis in the specialist sector.

Biologics (disease modifying antirheumatic drugs, bDMARD) have been in use in Germany for the treatment of rheumatoid arthritis (RA) since 2001, usually after failure of at least one conventional synthetic (cs)DMARD. We analyzed temporal changes in factors that influence the decision for either a first bDMARD or a further csDMARD.We analyzed data from 9513 bDMARD-naive RA patients in the German biologics register RABBIT who switched to a new therapy. For three recruitment periods (2001-2003, 2004-2006 and 2009-2015) factors influencing the therapeutic decision were analyzed by means of machine learning methods and logistic regression analysis.In all recruitment periods the number of previous csDMARDs, high dosages of glucocorticoids (7.5 mg/day) and a higher DAS28 (5.1) were significantly associated with the decision for a first bDMARD. Over time, the chance of receiving a bDMARD increased in patients with moderate disease activity, moderate glucocorticoid dosages (5-7.5 mg/day) and those with comorbidities, such as congestive heart failure or prior malignancy. Men had a higher chance of receiving a bDMARD than women only in the first recruitment period. Private health insurance, high education and gainful employment were significantly associated with more frequent prescription of bDMARDs in all recruitment periods.The time-dependent changes in the impact of disease activity, concomitant drugs, gender and comorbidity on the prescription of bDMARDs mirror the increasing therapeutic options and the growing experience in the application of the new substances in patients at higher risk. The influence of demographic and social factors may reflect safety concerns in patients at increased risk of adverse events but also the need to economize drug costs..

In a joint initiative by the boards of the German Society for Rheumatology (DGRh) and the Association of Rheumatology Clinics (VRA) the European "standards of care" for rheumatoid arthritis, recently suggested by the European Musculoskeletal Conditions Surveillance and Information Network (eumusc.net) and supported by the European League Against Rheumatism (EULAR), were translated and annotated. The recommendations include aspects of the management of the disease, actual medical care, and access to information - this includes all types of support people with RA need, and, last but not least communication of the necessary knowledge. Furthermore, health care structures such as the availability of medical staff with relevant expertise are also important.

Beim Pyoderma gangraenosum (PG) handelt es sich um ein seltenes Krankheitsbild in den chirurgischen Fachdisziplinen. Es wird uber einen 51-jahrigen Patienten berichtet, der mit dem Bild eines schweren septischen Schocks unter der Verdachtsdiagnose einer nekrotisierenden Fasziitis bei Infektion des „automated implantable cardioverter-defibrillator“ (AICD) auf die operative Intensivstation ubernommen wurde. Nachdem eine wochenlange invasive Therapie mit chirurgischen Wunddebridements und breiter antibiotischer Therapie nicht zur Verbessserung gefuhrt hatte, entschloss man sich zur Reevaluierung der Diagnose und stellte die Therapie unter der Verdachtsdiagnose eines PG auf eine konservative, immunsupressive Behandlung um. Hierunter zeigte sich eine rasche Besserung; der Patient konnte letztendlich in die Rehabilitation entlassen werden.

Die hypertrophe Osteoarthropathie (HOA) ist die klassische paraneoplastische Erkrankung in der Rheumatologie, charakterisiert durch die Trias aus Trommelschlegelfingern mit Uhrglasnageln, Gelenk- und Knochenschmerzen sowie proliferativer Periostitis. Diese Konstellation sollte Anlass zu einer intensiven Tumorsuche sein, wobei in der Regel intrathorakale Malignome zugrunde liegen. Wir berichten hier uber einen Patienten mit HOA im Rahmen eines neuroendokrinen Osophaguskarzinoms. Differenzialdiagnostisch kommen eine Reihe anderer nichtmaligner Erkrankungen der Lunge, des Herzens oder anderer Organe in Frage. Selten tritt auch eine primare, familiare Form der HOA auf, deren genetischer Hintergrund vor Kurzem entschlusselt wurde. Neue Erkenntnisse zur Pathophysiologie dieser Erkrankung haben auch zu einer Erweiterung der diagnostischen und therapeutischen Moglichkeiten gefuhrt.

In December 2014 a patient presented to our clinic with the clinical symptoms of vasculitis. However, treatment with glucocorticoids did not lead to any improvement; therefore, the differential diagnostics were extended to other indications and ultimately led to the diagnosis of scurvy.This article describes the clinical picture of scurvy and its relationship to rheumatic diseases based on a clinical case and additional information from the literature. Differences and similarities with important rheumatological disease symptoms are presented.Scurvy is a rare hypovitaminosis disease which can be manifested in different forms. In addition to vasculitis the symptoms can also resemble arthritis and hemarthrosis is a typical finding. These symptoms can be accompanied by unspecific manifestations, such as muscle pain and due to impaired collagen synthesis characteristic features, such as corkscrew hair can be observed. The causal therapy of scurvy is substitution of ascorbic acid.Scurvy is a rare differential diagnosis in the context of rheumatic diseases. The indications for scurvy can be a lack of response to immunosuppressive and immunomodulatory drugs as well as individual symptoms, such as corkscrew hair.

BACKGROUND AND OBJECTIVE Adult-onset Stilĺs disease (AOSD) is a rare entity. The course of the disease can be mild or severe, acute or chronic. The intention of this survey was to evaluate the longterm efficacy of TNF blockade in patients with severe and active AOSD. PATIENTS AND METHODS Eight patients with the diagnosis of AOSD, according to the diagnostic criteria developed by Yamaguchi in 1992, and pretreatment with either high dosage steroid or more intensive immunosuppressive therapy were treated with infliximab in a dosage of 3 - 5 mg/kg at time pointsduring week 0, 2 and 6. Later on, the treatment regimen was adapted to the individual needs of the patients. The follow-up period was between one and five years. RESULTS Seven patients responded to treatment with infliximab. Symptoms like fever, arthralgia, hepato-splenomegaly and serological parameters instantly improved. Five of these patients remained in remission over years after discontinuation of therapy. One of the responding patients needed permanent intensive treatment with TNF-blockers to control his severe chronic arthritis. Three patients experienced infusion reactions. One responding patient was therefore switched to etanercept and kept on this therapy. The one patient, who had not responded to infliximab also had no benefit from consecutive treatment with etanercept or adalimumab. CONCLUSION Anti-TNF therapy can have a lasting beneficial effect on the course of AOSD. Five of eight patients remained in remission even after termination of therapy.

Die etablierten therapeutischen Moglichkeiten zur Behandlung der ankylosierenden Spondylitis (AS) und der Psoriasisarthritis (PsA), die beide der Gruppe der Spondyloarthritiden (SpA) zugeordnet werden, sind unbefriedigend. Die Krankheitsverlaufe konnen durch die konventionelle Behandlung mit nichtsteroidalen Antiphlogistika (NSA) sowie durch Physiotherapie nur moduliert, nicht aber aufgehalten werden. Es besteht daher ein dringender Bedarf nach wirksameren Therapien. Seit einigen Jahren mehren sich die Hinweise darauf, dass der Tumornekrosefaktor α (TNFα) in der Pathogenese dieser Erkrankungen eine wichtige Rolle spielt. Entsprechend steht nun zunehmend der Einsatz von TNFα-Antagonisten (Antikorper bzw. Rezeptorfusionsproteine gegen TNFα) im Mittelpunkt therapeutischer Innovationen bei den Spondyloarthritiden und zwar sowohl fur den axialen als auch fur den peripheren Gelenkbefall. Im vorliegenden Beitrag werden verschiedene neue Studien zur Behandlung von SpA-Patienten mit TNFα-Antagonisten vorgestellt. Wenn weitere Untersuchungen diese optimistisch stimmenden Ergebnisse bestatigen, hatten Patienten mit schweren Verlaufen von AS und anderen Spondyloarthritiden nun eine hochwirksame neue Therapieoption, die einen echten medizinischen Fortschritt darstellt, von der die Patienten unmittelbar profitieren.

Objective: To compare the three year safety and efficacy of cyclosporin and parenteral gold in the treatment of early, active, severe rheumatoid arthritis (RA), and to study the reversibility of cyclosporin associated renal dysfunction in patients who discontinued cyclosporin treatment. Methods: The patients continued to receive cyclosporin or parenteral gold in an 18 month open extension to an 18 month randomised, parallel group study. The main efficacy variable was blinded evaluation of radiographic progression of joint damage. Safety variables included serum creatinine, calculated creatinine clearance, and blood pressure. Results: Radiographic progression during follow up was similar in both groups. About 60% of the patients in the intention to treat groups (n=272) and about half of the patients in the completer groups (n=114) had definite radiographic progression in joint damage (increases >6 in the Larsen-Dale score), and about one in three also had substantial progression (>18 increase in Larsen-Dale score). Both systolic and diastolic blood pressure were significantly increased in the cyclosporin group compared with the gold group, and 12/139 (9%) versus 3/139 (2%) (p=0.03) had notably raised blood pressure. The mean serum creatinine increased by 28% at the treatment end point in the cyclosporin group as compared with 7% in the gold group. The mean calculated creatinine clearance was reduced by 16% and increased by 1% in the cyclosporin and gold groups, respectively, at the end of the study. At the final follow up visit after discontinuation of cyclosporin (at least three months after treatment was stopped) the mean serum creatinine was increased by 15% and creatinine clearance reduced by 16%. Sustained increases in serum creatinine at this post-treatment end point were mostly seen in patients with a raised serum creatinine during treatment of at least 50%. Conclusion: Three year changes in radiographic damage during cyclosporin and parenteral gold were similar in patients with early, active RA. Abnormal renal function and raised blood pressure were often seen in the cyclosporin treated patients.

Ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are common inflammatory rheumatic diseases who belong to the spectrum of the spondyloarthritides (SpA). The therapeutic options for these conditions have been rather limited in the past decades. Standard treatment consists of drug therapy with nonsteroidal anti-inflammatory agents (NSAIDs), intraarticular steroids and physiotherapy. The peripheral symptoms of SpA respond partly to treament with disease modifying anti-rheumatic drugs (DMARDs). Several findings of the last years have indicated that TNFα plays a role in the pathogenesis of the SpA. Treatment with TNFα antagonists (monoclonal antibodies and receptor fusion proteins directed against TNFα) have been successfully used in patients with rheumatoid arthritis (RA), a pathogenetically distinct form of chronic joint inflammation. After stimulating pilot studies there is now increasing evidence from randomized controlled trials that these antagonists are very efficacious in the treatment of SpA, especially of AS and PsA, for both, axial and peripheral symptoms of disease. This therapy seems to be even more effective in SpA than in RA being comparable to the efficacy of corticosteroid therapy for polymyalgia rheumatica. There is international consensus that the availabilitiy of TNFα antagonists is a major breakthrough in the therapy of rheumatic diseases.

Peripheral arthritis is the most common presenting complaint in clinical rheumatology. Unequivocal identification of the underlying entity can be difficult, particularly at an early stage. Such cases are commonly referred to as undifferentiated peripheral inflammatory arthritis (UPIA). Since evidence-based recommendations for the clinical management of UPIA are lacking, this international 3e initiative convened 697 rheumatologists from 17 countries to develop appropriate recommendations.Based on a systematic literature research in Medline, EMBASE, Cochrane Library, and the ACR/EULAR abstracts of 2007/2008, 10 multinational recommendations were developed by 3 rounds of a Delphi process. In Germany, a national group of experts worked on 3 additional recommendations using the same method. The recommendations were discussed among the members of the 3e initiative and the degree of consensus was analyzed as well as the potential impact of the recommendations on clinical practice.A total of 39,756 references were identified, of which 250 were systematically reviewed for the development of 10 multinational recommendations concerning differential diagnosis, diagnostic and prognostic value of clinical assessments, laboratory tests and imaging techniques, and monitoring of UPIA. In addition, 3 national recommendations on the diagnostic and prognostic value of a response to anti-inflammatory therapy on the analysis of synovial fluid and on enthesitis were developed by the German experts based on 35 out of 5542 references.The article translates the 2011 published original paper of the international 3e initiative (Machado et al., Ann Rheum Dis 70:15-24, 2011) and reports the methods and results of the national vote and the additional 3 national recommendations.

Hepatitis C virus (HCV) infection is often associated with abnormal immunological responses. We describe four patients with vasculitic neurological signs and symptoms following HCV infection. A 56-year-old woman with HCV infection developed peripheral neuropathy characterized by asymmetric distal painful hypesthesia, dysesthesia and moderate motor weakness of the lower limbs. Serological examinations revealed cryoglobulinemia and low levels of complement C4. A biopsy of the sural nerve revealed vasculitic neuropathy. HCV infection associated immunomediated vasculitis was diagnosed. While steroid therapy was ineffective, treatment with interferon-alpha improved the neuropathy considerably without, however, eliminating HCV infection. A 62-year-old man with HCV infection developed peripheral sensory neuropathy. Complement C3 was slightly diminished. Nerve biopsy revealed vasculitic neuropathy. A 71-year-old woman developed chronic symmetric sensomotor polyneuropathy. HCV hepatitis followed blood transfusions. Cryoglobulins tested positive, consistent with type II cryoglobulinemia. Complements C3 and C4 were diminished. Inflammatory infiltrates in the sural nerve biopsy specimen led to the diagnosis of chronic vasculitic disorder. A 55-year-old woman with HCV infection developed vasculitis of the skin, connective tissue, visceral organs, and kidney, leading to hemodialysis. Neurologically she developed severe apathy and drowsiness, myoclonic jerks, exaggerated deep tendon reflexes, and positive pyramidal signs. Magnetic resonance imaging of the brain showed diffuse increased signal abnormalities involving supra- and infratentorial white matter suggesting cerebral vasculitis. Cryoglobulins were positive, complements C3 and C4 slightly diminished (54 mg/dl, 4.3 mg/dl). Supportive therapy resulted in neurological improvement. Treatment with interferon-alpha was discontinued because of agranulocytosis. In patients with peripheral neuropathy or signs of leucencephalopathy, a hepatitis C associated vasculitis should be considered in the differential diagnosis.

Die nephrogene systemische Fibrose ist ein erstmals im Jahr 2000 beschriebenes neues Krankheitsbild bei niereninsuffizienten Patienten, das durch eine Fibrosierung von Dermis und viszeralen Organen charakterisiert ist. Vor kurzem konnte die Atiologie dieser Erkrankung entschlusselt werden. Der Einsatz Gadolinium-haltiger Kontrastmittel bei der Magnetresonanztomographie kann bei eingeschrankter Nierenfunktion zu einer Ablagerung des Gadoliniums im Gewebe und zur Auslosung eines Fibroseprozesses fuhren. Zahlreiche Publikationen der letzten Monate unterstutzen diese Hypothese und haben zu aktuellen Empfehlungen der Gesundheitsbehorden fur einen restriktiven Gebrauch von Gadolinium bei niereninsuffizienten Patienten gefuhrt.

SUMMARY Objective. This study compared the progression of joint damage in patients with early active severe rheumatoid arthritis (RA) treated with cyclosporin or parenteral gold. Methods. In this open, randomized, multicentre study with a blinded radiological endpoint, 375 patients who had suVered from active severe RA for

Antibodies against citrullinated peptides are highly specific for rheumatoid arthritis. With second generation ELISA-kits, CCP-antibodies have a specificity of > 96 % and a sensitivity of 68 %. CCP-antibodies can be detected several years before the onset of clinical symptoms. They are, thus, ideally suited for the differential diagnosis between early forms of rheumatoid arthritis and other inflammatory arthritides. As CCP-antibodies are associated with aggressive and treatment resistant courses of rheumatoid arthritis, their high predictive value can be useful in therapeutic strategy decisions in order to verify early treatment with disease modifying drugs or biologicals in line with modern treatment approaches to start aggressive therapy early to prevent bone erosions. In contrast to their role in differential diagnosis and prediction of aggressive disease, however, CCP-antibodies are of no value in monitoring treatment as they do not change essentially over prolonged periods of time.

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.

IgG4-related disease is a systemic fibroinflammatory syndrome of unknown etiology characterized by local inflammatory swelling and tumefactive lesions in one or several organs. It unifies several diseases previously thought to be unrelated. Recently, diagnostic criteria for the disease have been formulated and were complemented by an international consensus on histopathological assessment. In general, the disease activity can be rapidly controlled by high doses of prednisolone (0.6 mg/kg body weight); however, relapses, either local or in other regions, are frequent during tapering of the steroid dose. Commonly used steroid-sparing agents are only partially effective. Persistent local inflammatory activity may result in permanent organ damage. In refractory cases rituximab treatment has been used with good success. In the long-term care of affected patients a probable increased risk of malignancies (e.g. solid tumors and lymphoma) requires attention.

Osteonecrosis (ON) is a well-known complication in patients with systemic lupus erythema tosus (SLE) often associated with steroid therapy. In a cohort of 280 SLE patients followed over the last 10 years, seven patients developed symptomatic ON, one of them after septic arthritis of the hip. Two other patients developed ON several years after discontinuing steroids. One patient developed ON of both humeral and femoral heads within a few months after the diagnosis of SLE. When we compared the cumulative steroid doses taken by our patients with those described in other reports (43 700 mg and 45 300 mg, respectively), our patients received less steroids (38 834 mg). We found no increased fre quency of Raynaud's phenomenon, leukopenia, anti-phospholipid antibodies, or a flare of SLE activity in our patients with ON, factors which have been reported to be associated with ON. Various pathogenic mechanisms, which could lead to ON in SLE patients are discussed.

Due to the unknown etiology of RA, specific treatment is not available. Recently, in a double-blinded, placebo-controlled clinical trial, in vivo blockade of TNF-alpha by a single infusion of a chimeric TNF-alpha-blocking mAb, cA2, has proven to be highly effective in the treatment of RA. In parallel to this trial, we tested the consequences of cA2 infusion in ex vivo and in vitro experiments. In this paper, we describe an increase in CD4+ and CD8+ T lymphocyte counts on day 1 and a marked decrease in monocyte counts preferentially on day 7 after cA2 treatment, without major changes in B lymphocyte or NK cell counts. In addition, we found an increased responsiveness of PBMC to CD28 mAb/PMA, but not to CD3 mAb, superantigen staphylococcus enterotoxin B, or PHA on day 1 after infusion. The increase in DNA synthesis of PBMC was paralleled by increased IL-2 mRNA and IL-4 mRNA expression and IL-2 protein secretion in culture supernatants after in vitro stimulation of PBMC with CD28 mAb/PMA. In PBMC, we did not find any significant changes in mRNA or protein expression of CD28 Ag or CD28 ligands, B7-1 and B7-2. Serum concentrations of IL-1 beta, IL-6, and soluble CD14 were significantly diminished after in vivo TNF-alpha blockade. We did not see relevant changes in granulocyte function in vitro after cA2 infusion. Finally, we observed a statistically significant decrease in slCAM-1 molecules in the serum of patients treated with verum compared with that in the serum of subjects given placebo. This change in slCAM-1 concentration was evident on days 1 and 7 after the infusion of 10 mg/kg cA2, whereas it occurred only on day 7 in the serum of patients treated with the low dose (1 mg/kg) of cA2.

Als eine „seltene Erkrankung“ (engl.: orphan disease) definiert die EU eine Krankheit, die „lebensbedrohend ist oder eine chronische Invaliditat nach sich zieht und von der . . . in der Gemeinschaft nicht mehr als funf von zehntausend Personen betroffen sind“ [1].Wahrend einAllgemeinarztwahrend seiner Berufstatigkeit die allermeisten dieser Erkrankungen nie oder allenfalls sporadisch zu sehen bekommt, stellt sich dies in der rheumatologischen Praxis ganz anders dar. Sowohl fur internistische als auch padiatrische Rheumatologen erfullt die uberwiegende Mehrzahl der Krankheitsbilder, mit denen sie Tag fur Tag zu tun haben, die oben genannte Definition und auch der orthopadisch tatige Rheumatologe hat haufig mit den Manifestationen solch seltener Erkrankungen am Stutzund Bewegungsapparat zu tun.

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.

Of all inflammatory rheumatic diseases gout has the highest prevalence. Patients with intermittent acute gout attacks are usually treated by primary care physicians. However, in cases of insufficient long-term control of serum uric acid levels, complications or atypical clinical manifestations may necessitate consultation with a rheumatologist in the further course of the disease. An oligoarticular or polyarticular presentation can give rise to the initial suspicion of rheumatoid or psoriatic arthritis. In these cases a careful clinical work-up supported by laboratory and imaging investigations is necessary and synovial fluid analysis is usually required. As in other rheumatic diseases extra-articular manifestations are of utmost importance for morbidity and mortality. Gout is a complex metabolic and inflammatory disease and besides articular symptoms the renal and cardiovascular effects of hyperuricemia are particularly relevant for the overall prognosis.