[Current state, goals and quality standards of outpatient care in rheumatology: position paper of the Professional Association of German Rheumatologists (BDRh)]. / Aktueller Stand, Ziele und Qualitätsstandards der ambulanten Versorgung in der Rheumatologie: Positionspapier des Berufsverbandes der deutschen Rheumatologen (BDRh).

Even in the era of modern guidelines, the treatment of rheumatic diseases is only as good as the framework of rheumatological care within which the treatment is carried out. The access to high-quality medical treatment for all patients is therefore essentially decisive for the prognosis of the patients. This article describes the current state of outpatient treatment in rheumatology and demonstrates which quality projects, such as treatment contracts, outpatient specialized medical treatment (ASV), digitalization and training as specialized rheumatological assistant (RFA), have been created in order to ensure the treatment of our patients. Furthermore, standards are defined that can guarantee a contemporary and guideline-conform treatment in outpatient rheumatological units. As an example it is an affirmation of the Professional Association of German Rheumatologists (BDRh) for ensuring optimal care for all rheumatology patients through early or emergency rheumatology clinics, treat to target, appropriate delegation of medical duties and diversification of treatment, thus an assurance of the quality and comprehensive treatment in rheumatology. The important topic of safeguarding the next generation of rheumatologists, which is indispensable for this, is also discussed.

[Successful treatment of adult Still's disease with tofacitinib in a HIV-2 positive female patient]. / Erfolgreiche Behandlung eines adulten Morbus Still mit Tofacitinib bei einer HIV-2-positiven Patientin.

A 46-year-old female patient with a known HIV-2-infection suffered from adult onset Still's disease, which was initially complicated by a macrophage activation syndrome (MAS). The required glucocorticoid treatment induced a psychosis and the patient developed an aversion to glucocorticoids. After failure of treatment with anakinra, an alternative option with the JAK-inhibitor tofacitinib was introduced because of the short half-life and to reduce glucocorticoid exposure. A switch to tofacitinib was only successful after an overlapping treatment with anakinra and tofacitinib for 3 weeks. The patient is currently being treated with monotherapy with tofacitinib as well as NSAID on demand, is in stable remission and can continue working as normal.

[Evidence-based treatment recommendations for familial Mediterranean fever : A joint statement by the Society for Pediatric and Adolescent Rheumatology and the German Society for Rheumatology]. / Evidenzbasierte Therapieempfehlungen für das familiäre Mittelmeerfieber : Eine gemeinsame Stellungnahme der Gesellschaft für Kinder- und Jugendrheumatologie und der Deutschen Gesellschaft für Rheumatologie.

BACKGROUND: Familial Mediterranean fever (FMF) in Germany is a rare, genetically linked disease of childhood and adolescence, which is characterized by recurrent febrile episodes and clinical signs of peritonitis, pleuritis and arthritis. Treatment with colchicine is effective and well-tolerated in the majority of patients; however, some patients do not sufficiently respond to this treatment or are intolerant to colchicine. For these patients first-line treatment with biologics which block interleukin-1 can be used. OBJECTIVE: The aim was to formulate evidence-based treatment recommendations for patients with an insufficient response and intolerance to colchicine treatment. METHODS: Based on a literature search and the European League Against Rheumatism (EULAR) recommendations on FMF from 2016 the appointed members of the Society for Pediatric and Adolescent Rheumatology (GKJR) and the German Society for Rheumatology (DGRh) convened to work out and form a consensus in a joint statement on evidence-based treatment recommendations on FMF. RESULTS: After intensive discussions all decisions were in concordance. A total of 5 superordinate principles and 10 recommendations were agreed upon. DISCUSSION: The joint activities of the GKJR and the DGRh were successfully concluded in a timely manner. The recommendations form a good basis for optimal treatment of all age groups of patients with FMF.

[Rheumatoid arthritis-mimics : When appearances are deceptive]. / Rheumatoide Arthritis ­ Mimics : Wenn der Schein trügt.

Rheumatology represents a discipline full of differential diagnoses. Even for classical diseases, such as rheumatoid arthritis as the most frequent chronic inflammatory joint disease and described so clearly in many textbooks, it is not uncommon that it can be a diagnostic challenge in daily practice. This applies to arthritic joint involvement and also to frequently associated extra-articular manifestations. The patient history and results of the clinical examination are essential; however, laboratory and imaging findings often make a significant contribution to confirming the diagnosis, especially in early phases of the disease. This article, which makes no claims to completeness, focuses on diseases that in the opinion of the authors can imitate rheumatoid arthritis due to similar joint and other organ manifestations. These include metabolic, inflammatory infective and non-infective as well as tumorous diseases. A misinterpretation as rheumatoid arthritis as a rule leads to long-term and severe consequences for affected patients. Thus, the diagnosis of rheumatoid arthritis should be questioned and re-evaluated in cases of unusual accompanying symptoms, atypical course of disease and a lack of response to standard treatment approaches.

[Clinical aspects and genetics of proteasome-associated autoinflammatory syndromes (PRAAS)]. / Klinik und Genetik bei Proteasomen-assoziierten autoinflammatorischen Syndromen (PRAAS).

Functional disorders of the proteasome can have a severe impact on the innate immune system. Characterized by an autosomal recessive mode of inheritance, this novel type of interferonopathy is considered to be a spectrum of diseases of proteasome-associated autoinflammatory syndromes (PRAAS). Accumulation of ubiquitinated proteins and the induction of type I interferon (IFN) genes seem to play a role in the pathogenesis. The typical clinical manifestations are lipodystrophy, skin, joint and muscle involvement accompanied by a remarkable variability of other associated symptoms. This article provides an overview on currently known molecular alterations as well as clinical similarities and differences of PRAAS. Furthermore, the reported effects of the immunosuppressive therapy approaches used so far are summarized.

Usefulness of power Doppler ultrasound for prediction of re-therapy with rituximab in rheumatoid arthritis: a prospective study of longstanding rheumatoid arthritis patients.

OBJECTIVE: To assess the value of gray-scale (GS) and power Doppler (PD) ultrasound (US) in detecting inflammatory/destructive changes and for prediction of necessity of re-therapy with rituximab (RTX) in patients with rheumatoid arthritis (RA) over 1 year of followup. METHODS: GSUS and PDUS were performed to assess synovitis, tenosynovitis, and erosions on the clinically dominant hand and forefoot of 20 patients with RA before and after therapy with RTX. US parameters were compared with clinical (Disease Activity Score in 28 joints, tender/swollen joint counts, and patients' visual analog scale of disease activity) and laboratory parameters (C-reactive protein level and erythrocyte sedimentation rate). Results were compared for patients with and without re-therapy with RTX. RESULTS: Significant decreases in clinical and laboratory parameters were observed after 6 and 12 months. US synovitis scores significantly decreased after 6 and 12 months (P < 0.05 for each). Regarding patients who received re-therapy between 6 and 9 months after the start of therapy (n = 9), a fair therapy response was still detectable before re-therapy. In these patients, PD-positive synovitis was the only parameter that increased up to the 6-month examination. All patients negative for rheumatoid factor and anti-cyclic citrullinated peptide (n = 4) were in the group of patients receiving a second course of treatment. Seropositive patients showed a better response to treatment with less need for re-therapy. CONCLUSION: Response to therapy was measurable by clinical and laboratory parameters as well as by US. Since PDUS was able to detect the onset of disease activity before worsening of clinical symptoms occurred, PDUS is most helpful in evaluating disease activity and making earlier therapy decisions.

[New aspects on the pathogenesis of myositis]. / Neues zur Pathogenese der Myositiden.

Idiopathic inflammatory myopathies (IIM) are chronic inflammatory diseases of muscle characterized by proximal muscle weakness. There are three main groups of diseases, dermatomyositis, polymyositis and inclusion body myositis. The muscle tissue is invaded by the humoral autoantibody producing immune system (B-cells) and by the cellular immune system with autoaggressive and inflammation modulating cells (e.g. dendritic cells, monocytes/macrophages, CD4 + and CD8 + T-cells and natural killer cells). The presence of specific or associated autoantibodies and inflammatory cellular infiltrates with cytotoxic and immune autoreactive properties are characteristic for IIM diseases. The pathogenesis is still unknown; nevertheless, there are several hints that exogenic factors might be involved in initiation and disease progression and bacterial, fungal and viral infections are thought to be possible initiators. Up to now information on prognostic markers to help with decision-making for individual treatment are limited. In addition, there has been only limited therapeutic success including conventional or novel drugs and biologicals and comparative validation studies are needed using similar outcome measurements. Moreover, to facilitate the use and development of novel therapies, elaboration of intracellular and cell-specific regulation could be useful to understand the etiopathogenesis and allow a better diagnosis, prognosis and possibly also a prediction for individualized subgroup treatment.

[Anticytokine therapy]. / Antizytokintherapie.

Anticytokine therapies have revolutionized the treatment of chronic inflammatory diseases, particularly autoimmune diseases such as rheumatoid arthritis. As the first introduced principle of cytokine blockade in the 1990s, tumor necrosis factor (TNF)-α antagonists still represent the leading anticytokine therapy. There are currently five TNF antagonists available with indications in the fields of rheumatology, dermatology, and gastroenterology. Other therapeutic approaches have been introduced in the last 10 years, e.g., the blockade of interleukin (IL)-1, IL-6, and IL-12/23. The advantages of cytokine blockers are their rapid onset of action with high response rates and a tolerable safety profile. Nevertheless, anticytokine therapy can cause increased rates of tuberculosis and hepatitis B infections or reactivation. An appropriate screening before therapy is mandatory, and thorough monitoring of the disease course before and during therapy is also important. The development of further anticytokine drugs for the induction and maintenance of remission is, therefore, required.

Unexplained recurrent fever: when is autoinflammation the explanation?

Recurrent fever can be the sole or leading manifestation of a variety of diseases including malignancies, autoimmune diseases and infections. Because the differential diagnoses are manifold, no formal guidelines for the approach of patients with recurrent fever exists. The newly recognized group of autoinflammatory diseases are often accompanied by repetitive fever attacks. As these episodes are frequently associated by a variety of divergent presentations, the differentiation of other causes for febrile illnesses can be difficult. In this article, we first review disease entities, which frequently present with the symptom of recurrent fever. In a next step, we summarize their characteristic pattern of disease presentation. Finally, we analyse key features of autoinflammatory diseases, which are helpful to distinguish this group of diseases from the other causes of recurrent fever. Recognizing these symptom patterns can provide the crucial clues and, thus, lead to the initiation of targeted specific diagnostic tests and therapies.

[Personalized medicine for rheumatoid arthritis : serological and clinical patient profiles to optimize B and T cell targeted therapy]. / Personalisierte Medizin bei der rheumatoiden Arthritis : serologisch-klinische Patientenprofile in der Optimierung der B- und T-Zell-gerichteten Therapie.

Nowadays B and T-cell directed biologics in addition to TNF inhibitors are established as effective and safe treatment options for rheumatoid arthritis. As shown by the approval of rituximab for the treatment of systemic vasculitis, these drugs can also be useful for the treatment of other systemic autoimmune diseases; however, to optimize therapeutic strategies, predictive factors for treatment response as well as a good characterized safety profile are essential. So far implementation of real personalized medicine is not feasible in the field of rheumatology, but first biomarkers have already been identified and provide promising results. In this context, it has been shown that a B-cell directed therapy with rituximab is more effective in seropositive patients with rheumatoid arthritis. In addition, characterization of the cytokine milieu as well as of circulating and tissue infiltrating B and T-cell subsets might be useful for prediction of treatment response in the near future.

[Therapeutic strategies in rheumatoid arthritis]. / Therapiestrategien bei rheumatoider Arthritis.

Rheumatoid arthritis is the most common chronic inflammatory-rheumatic joint disease. If untreated, patients develop radiologically detectable progressive joint destruction. Rheumatoid arthritis has considerable socioeconomic importance, since a majority of patients are affected at employable age and can be significantly disabled over the course of the disease. Therefore, an appropriate early intervention with disease modifying anti-rheumatic drugs as well as ergo- and physiotherapy plays an important role for the prognosis. In the past few years, the introduction of novel drugs has improved the treatment opportunities markedly. This progress was the basis for new treatment strategies of tight disease control with the goal of disease remission.

Effectiveness and safety of the interleukin 6-receptor antagonist tocilizumab after 4 and 24 weeks in patients with active rheumatoid arthritis: the first phase IIIb real-life study (TAMARA).

OBJECTIVES: To confirm the effectiveness and safety of the interleukin 6-receptor antagonist tocilizumab in patients with rheumatoid arthritis (RA) in a setting close to real-life medical care in Germany. METHODS: A multicentre open-label phase IIIb study was undertaken. Patients with active RA with a 28-joint Disease Activity Score (DAS28) >3.2 despite previous disease-modifying antirheumatic drugs (DMARDs) were treated with tocilizumab 8 mg/kg every 4 weeks. The primary end point was the proportion of patients achieving LDAS ≤3.2 at week 24; secondary end points included American College of Rheumatology (ACR), European League Against Rheumatism (EULAR) or Clinical Disease Activity Index (CDAI) responses and decrease in acute phase. Analyses in subgroups such as rheumatoid factor (RF)-positive versus RF-negative patients and patients with an inadequate response to treatment with DMARDs (DMARD-IR) versus those with an inadequate response to tumour necrosis factor (TNF) antagonists (TNF antagonist-IR) were performed. Safety was assessed by adverse event documentation. RESULTS: 286 patients were treated and 83.6% completed the study. 41.6% had previously been treated with TNF antagonists. 57% of the intention-to-treat patients achieved the primary end point of LDAS, 47.6% achieved DAS remission <2.6 and a EULAR 'good response' was achieved by 54.9%; ACR50/70 response rates at week 24 were 50.7% and 33.9%, respectively. The mean±SD decrease in CDAI from baseline to week 24 was 71±29%. C reactive protein levels normalised rapidly within 1 week. Major improvements in fatigue, pain and morning stiffness were observed in the first 4 weeks and further improved until week 24. DAS28, EULAR and ACR responses at week 24 did not differ between RF-positive and RF-negative patients. TNF antagonist-naive patients responded better than patients who had previously failed on TNF antagonists. The safety profile of tocilizumab was comparable to that previously observed in the phase III trial programme. Serious infections were observed in 3.1% of patients. CONCLUSIONS: Tocilizumab is highly effective in a setting close to real-life medical care with a rapid and sustained improvement in signs and symptoms of RA. A manageable safety profile was seen over the 24-week study period.

[Rituximab]. / Rituximab.

Rituximab as a monoclonal antibody against CD20 was approved for treatment of patients with rheumatoid arthritis (RA) with inadequate response to or contraindication for the use of a TNF blocker. This article focuses on current results from clinical trials at different developmental stages as well as from registry data in anti-TNF non-responders regarding the documented efficacy with respect to RA activity, radiological progression and improvement of functional indices. The available safety data for rituximab for this particular indication showed that the overall risk of infection, including severe manifestations, is not further increased. The occurrence of progressive multifocal leukoencephalopathy (PML) after rituximab requires further observation; the risk has currently been estimated at about 1:15.000-20.000 of RA patients treated. Of relevance, decreased IgG levels prior to treatment have been reported to be associated with a substantially increased risk for infections, and therefore, in such cases other treatment options should be considered.

[Diseases of the outer eye in rheumatoid arthritis]. / Erkrankungen des äusseren Auges bei rheumatoider Arthritis.

Eye involvement is a frequent finding in patients with rheumatoid arthritis and may represent the leading clinical manifestation of disease. In this context, all components of the visual organ might be affected. The main spectrum of eye involvement comprises keratoconjunctivitis sicca, episcleritis and scleritis as well as ulcerative keratitis. As with the underlying disease, autoimmune reactions based on a patient's genetic predisposition are assumed to be of significance in disease pathogenesis. Emerging evidence also points to additional morphological and physiological ocular characteristics in the pathogenesis of the various ocular pathologies. This article gives an overview of clinical aspects, pathogenetic background as well as therapeutic options for ocular involvement in rheumatoid arthritis.