Ultrasonographic findings in diabetic cheiroarthropathy: a pilot study.

OBJECTIVE: Diabetic cheiroarthropathy (DCA) is one of the musculoskeletal manifestations of diabetes mellitus. It is clinically diagnosed using the prayer and tabletop signs. The clinical appearance, however, mimics autoimmune-mediated polyarthritis of the hands and fingers. It is therefore crucial to positively identify DCA patients. METHOD: We used high-frequency B-mode ultrasound to investigate 14 patients with DCA and seven non-DCA diabetics with anti-cyclic citrullinated peptide antibody-positive rheumatoid arthritis (RA). We recorded the frequency of synovitis in radiocarpal, metacarpophalangeal, and proximal interphalangeal joints, the presence of tenosynovitis of the finger flexor tendons, echogenicity of the synovia and the flexor tendon sheaths, and soft tissue alterations in the digits. We compared our findings between groups to determine sonographic characteristics of DCA. RESULTS: A low rate of small finger joint involvement in the presence of a high rate of finger flexor tendinopathy showed a high association with DCA in correlation (p = 0.002) and regression analysis (p < 0.001). Tendon sheaths were significantly more often hyperechoic and proliferative in DCA compared to RA (p = 0.008), and hypoechoic soft tissue alterations were almost exclusively seen in DCA patients (p = 0.003). Radiocarpal joint involvement and its echogenicity did not differ between groups. CONCLUSION: Ultrasonography shows typical features in DCA, and is capable of discriminating DCA from non-DCA patients with RA and diabetes.

Utility of serum complement factors C3 and C4 as biomarkers during therapeutic management of giant cell arteritis.

OBJECTIVE: There is a strong unmet need for biomarkers in giant cell arteritis (GCA), as C-reactive protein (CRP) may be unreliable in patients treated with Tocilizumab (TCZ). We aimed to assess whether C3 and C4 are useful biomarkers in GCA patients, particularly in those treated with TCZ. METHOD: We retrospectively enrolled all patients who underwent C3 and C4 measurement at baseline. All patients were evaluated at 3, 6, 12, and 24 months after diagnosis, as part of routine follow-up. Two assessments after the end of the observational period, in case of further relapses, were also included. RESULTS: At baseline, mean ± sd levels (mg/dL) of C3 (133 ± 28.99) and C4 (25.9 ± 9.04) were within normal ranges. During follow-up, C3 and C4 decreased in patients attaining remission (107.07 ± 19.86, p = 0.0006; 19.86 ± 10.27, p = 0.01, respectively) and sustained remission (95.85 ± 18.04, p = 0.001; 15.61 ± 9.75, p = 0.006). In TCZ-treated patients, even stronger decreases in C3 (83.11 ± 19.66, p = 0.001) and C4 (8.26 ± 3.83, p < 0.0001) were observed, and their values were not correlated with CRP or erythrocyte sedimentation rate. CONCLUSION: C3 and C4 do not seem useful in the diagnosis of GCA, as normal values do not rule out active vasculitis. However, C3 and C4 correlate with disease activity. As the low C4 levels found in TCZ-treated patients are not correlated with CRP, C4 should be evaluated as a potential biomarker of disease activity and treatment response.

[Quality in acute inpatient rheumatology 2021 : Current aspects of the KOBRA quality label of the Association of Rheumatological Acute Care Clinics]. / Qualität in der akutstationären Rheumatologie 2021 : Aktuelle Aspekte zum KOBRA-Qualitätslabel des Verbandes Rheumatologischer Akutkliniken (VRA e.V.).

A comprehensive health policy quality campaign launched in 2021 aims to improve the quality and transparency of hospital care for people with diseases in Germany. Legal requirements for minimum volumes and the expansion of quality contracts between cost units and hospitals as well as the use of quality indicators relevant to planning for demand-oriented and quality-oriented further development of inpatient care will increase competition in the quality of care between hospitals. The topic of development and definition of quality in medicine was also comprehensively addressed by the Association of Rheumatological Acute Care Clinics (VRA) shortly after its foundation in 1998. At the center of acute inpatient quality management are binding structural criteria linked to the continuous outcome benchmarking in acute rheumatology care (KOBRA) project launched in 2003 in rheumatology (and continuously implemented to date) measuring process and outcome quality. Based on this framework (fulfillment of the structural quality and participation in the KOBRA project) successfully participating rheumatology units can acquire the KOBRA seal of approval for 2 years at a time, which is awarded by the project management, the aQua Institute. The outstanding position of the project is exemplified by data evaluation on treatment change in active rheumatoid arthritis, diagnosis confirmation of connective tissue diseases and vasculitis during the inpatient stay as well as on participatory decision-making processes concerning rheumatoid arthritis (referring to the results of the data collection period 2018). By anchoring projects for structural, process and outcome quality acute inpatient rheumatology is well prepared for the paradigm shift demanded by health policies. Additionally, the KOBRA project is a good prerequisite to meet the requirements concerning quality management fixed in the Federal Joint Committee (G-BA) guidelines for recognition as a rheumatology center.

[Future of acute inpatient rheumatology in Germany : Statement of the Boards of the German Society for Rheumatology and the Association of Rheumatological Acute Clinics on hospital planning North-Rhine/Westphalia 2019 for the discipline rheumatology]. / Zukunft der akutstationären Rheumatologie in Deutschland : Stellungnahme der DGRh- und VRA-Vorstände zur Krankenhausplanung NRW 2019 für den Leistungsbereich Rheumatologie.

In September 2019 the Ministry of Labor, Health and Welfare (MAGS) of North-Rhine/Westphalia (NRW) published an expert report on hospital planning. In this report a fundamental reform of hospital planning was recommended, in that a requirements planning should be carried out in the future on the basis of a detailed designation of disciplines and organizational groups. At the request of the MAGS NRW, the German Society for Rheumatology (DGRh) with the support of the Association of Rheumatological Acute Clinics (VRA) has also commented on this issue.

Treatment of Giant Cell Arteritis and Takayasu Arteritis-Current and Future.

PURPOSE OF REVIEW: Guidelines for the management of large vessel vasculitides have been recently updated by several scientific societies. We have evaluated the current recommendations for treatment of giant cell arteritis (GCA) and Takayasu arteritis (TA) and addressed potential future therapeutic strategies. RECENT FINDINGS: While glucocorticoids (GCs) remain the gold standard for induction of remission, many patients relapse and acquire high cumulative GC exposure. Thus, GC-sparing therapies such as methotrexate are recommended for selected patients with GCA and all patients with TA. Recent high-quality evidence shows that tocilizumab is an effective GC-sparing agent in GCA. Non-biologic and biologic immunomodulators also appear to have GC-sparing properties in TA. Tocilizumab is now considered to be part of the standard treatment for GCA, particularly with relapsing disease, but questions on its use such as length of treatment and monitoring of disease activity remain open. High-quality evidence to guide treatment of TA is still lacking.

[ANCA diagnostics in vasculitis]. / ANCA-Diagnostik bei Vaskulitiden.

The cornerstone of the laboratory diagnostics of small vessel vasculitis is the detection of antineutrophil cytoplasmic antibodies (ANCA). The current international consensus recommendations suggest that proteinase 3 (PR3) and myeloperoxidase (MPO) ANCA immunoassays should be used as a first-line test if there is a justified suspicion of ANCA-associated vasculitis (AAV). A second method is only recommendable when the immunoassay shows a negative or borderline result. The precise identification of all patients with active AAV and avoidance of misdiagnoses due to false positive ANCA measurements is achieved when the ANCA determination is limited to defined clinical situations, which are indicative for AAV. There is increasing evidence that the specificity of ANCA to define homogeneous groups of patients could be better with respect to the prognosis than the clinical subtype.

[Treatment of Takayasu arteritis]. / Therapie der Takayasu-Arteriitis.

Despite advances in the diagnosis and treatment, the mortality rate of Takayasu arteritis (TAK) is still elevated even today. The diagnosis is often made after a long time delay and the course of the disease is characterized by progressive structural vascular lesions. Recently, new recommendations for the management of large vessel vasculitis were published by the European League Against Rheumatism (EULAR). For induction of remission oral glucocorticoids (GC) are administered in an initial daily dose of 40-60 mg. As experience has shown that the cumulative GC demand in TAK is high, GC-sparing treatment with moderately potent immunosuppressants, such as methotrexate, azathioprine and mycophenolate mofetil is recommended from the time of initial diagnosis. In cases of a relapsing course, tocilizumab or tumor necrosis factor (TNF)-alpha inhibitors can be used as an additive off-label treatment. If vascular stenoses persist despite supposedly sufficient inflammation control and if these stenoses are symptomatic, vascular surgery or interventional treatment procedures can be indicated. Such revascularization or even surgical procedures for the treatment of aneurysms should be performed during phases of sufficient drug control of the vasculitis. In quite a few patients progressive vascular lesions continue to develop despite clinical and laboratory analytical remission. Due to the poor correlation of clinical symptoms and acute phase markers with the progression of vascular lesions, the distinction between active and inactive diseases is often a challenge in the clinical practice. Imaging studies can then support therapeutic decisions but are not yet formally and comprehensively validated in the long-term course of TAK.

[Treatment of giant cell arteritis and polymyalgia rheumatica]. / Therapie der Riesenzellarteriitis und Polymyalgia rheumatica.

Patients with untreated active giant cell arteritis (GCA) are at high risk of permanent vision loss. Therefore, treatment with glucocorticoids should be immediately initiated at an initial dose of 40-60 mg prednisolone equivalent dose per day. Once remission is achieved, the prednisolone dose should be reduced to 15-20 mg within 2-3 months and then to ≤5 mg per day within 1 year. Glucocorticoid-sparing treatment with tocilizumab or alternatively methotrexate should be initiated in patients with an increased risk or pre-existing complications of glucocorticoid treatment and patients with relapse. In polymyalgia rheumatica, prednisolone dosages of 15-25 mg/day are sufficient. After achieving remission, the dose should then be reduced to 10 mg within 4-8 weeks and then to 1 mg per month thereafter. Glucocorticoid-sparing treatment with methotrexate should be initiated in patients with an increased risk or existing complications of glucocorticoid treatment, relapse or increased glucocorticoid requirements.

[What are the indications for rescue procedures? : Systemic rheumatic diseases in the intensive care unit]. / Was sind die Indikationen für Rescue-Verfahren? : Rheumatische Systemerkrankungen auf der Intensivstation.

Severe, organ-threatening and life-threatening manifestations of inflammatory rheumatic diseases, such as diffuse alveolar hemorrhage in the context of small vessel vasculitis, sometimes inadequately respond to immunosuppressive treatment. In the case of an immanent or already occurring organ failure, immunosuppressive treatment may need to be supplemented with rapidly effective rescue treatment procedures. Due to the rarity of many rheumatic diseases, the evidence for the use of rescue treatment, such as plasmapheresis, extracorporeal membrane oxygenation (ECMO) and the administration of intravenous immunoglobulins (IVIG), is relatively low for many indications. The use of plasmapheresis is considered useful in acute anti-glomerular basement membrane (GBM) disease (Goodpasture's syndrome) or catastrophic antiphospholipid antibody syndrome (APS). The use of ECMO treatment may be considered for persistent respiratory failure despite mechanical ventilation due to diffuse alveolar hemorrhage or acute respiratory distress syndrome (ARDS). Administration of IVIG is indicated for acute cardiac involvement in Kawasaki's disease and may be considered in catastrophic APS and refractory myositis.

[Outpatient specialist medical treatment (ASV)-a new treatment level in rheumatology]. / Ambulante spezialfachärztliche Versorgung (ASV) ­ eine neue Versorgungsebene in der Rheumatologie.

Since April 2018, the new third level care model of outpatient specialist care (ASV) according to §116b of the Social Code Book V (SGBV) has been available for patients with chronic inflammatory rheumatic diseases in Germany. Not only is a multiprofessional cooperation between the disciplines involved in treating rheumatic diseases promoted but also the cooperation between specialized rheumatologists and other specialists in private practice and in hospitals is encouraged. As budget capping limiting services and number of cases do not apply in ASV, a significant improvement of patient care in rheumatology is expected due to an increase in provider capacity. At the end of May 2019, 72 rheumatologists in the first 9 newly approved ASV teams had qualified for this new care concept. Bureaucratic obstacles have so far delayed the implementation of ASV. Difficulties arose in building a team with different specialties, in the process of registration of the teams and the assessment of the registration by certain regional boards responsible for access control. The national associations of rheumatologists, the Professional Association of German Rheumatologists (BDRh), the VRA (Verband der Rheumatologischen Akutkliniken e. V.) and the German Society of Rheumatology (DGRh) campaign for an easier admission of providers to the ASV and for adequate financing of all specialties involved in the ASV. The aim is to realize the chance of the ASV for better rheumatological care nationwide with shorter waiting times for a medical appointment and a better cooperation between specialists.

[ANCA-associated vasculitides : State of the art]. / ANCA-assoziierte Vaskulitiden : State of the Art.

Granulomatosis with polyangiitis (GPA, formerly Wegener's granulomatosis) and microscopic polyangiitis (MPA) are associated with the detection of antibodies against neutrophilic cytoplasmic antigens (ANCA) and are referred to as ANCA-associated vasculitides (AAV). In the event of the clinical suspicion of AAV the ANCA should first be determined by means of an antigen-specific immunoassay for proteinase 3­ANCA and myeloperoxidase-ANCA, according to current consensus recommendations. The diagnosis of AAV should also be confirmed by biopsy if possible. The classification criteria for AAV are currently being revised. Diagnostic criteria do not exist. The standard induction therapy consists of rituximab or cyclophosphamide, each in combination with glucocorticoids (GC). In the absence of severe organ involvement, methotrexate can alternatively be used. Recent study data suggest that additive plasmapheresis does not improve the long-term outcome. After remission, remission-preserving treatment with azathioprine, methotrexate or rituximab should be given for at least 48 months. The risk of severe infections is markedly increased, especially during the remission induction phase but can also be reduced during treatment with rituximab by the prophylactic administration of trimethoprim-sulfamethoxazole. In view of the increased risk of infection, GC-reduced or GC-free treatment regimens are currently the focus of clinical development.

[Differential diagnosis of hypereosinophilia]. / Differenzialdiagnose der Hypereosinophilie.

Eosinophilia is defined as an elevated absolute number of eosinophilic leukocytes in peripheral blood or tissue. Its absolute number also defines the grade of eosinophilia. The main causes are allergic (including drug side effects) and infectious triggers but malignant and autoimmune diseases can also result in eosinophilia. Severe eosinophilia with the number of eosinophils >5000/µl are mostly caused by myeloproliferative disorders, eosinophilic granulomatosis with polyangiitis or during tissue migration in parasitic tissue infections. Hypereosinophilic syndrome is defined as eosinophilia with >1500 eosinophils/µl and a duration of more than 6 months by exclusion of parasitic infections, allergies or other causes of tissue eosinophilia with end-organ damage. For the diagnosis of a persistent eosinophilia a detailed medical history and physical examination should be followed by early organ screening, infection diagnostics especially for helminth infections and hematological laboratory analyses including bone marrow investigations.

[Paradigm shift in ANCA diagnostics : New international consensus recommendations]. / Paradigmenwechsel in der ANCA-Diagnostik : Neue internationale Konsensusempfehlungen.

BACKGROUND: Up to now indirect immunofluorescence (IIF) followed by an antigen-specific assay specific for proteinase 3 (PR3) or myeloperoxidase (MPO) has been the standard method for the detection of antineutrophil cytoplasmic antibodies (ANCA). The development of more sensitive and highly specific PR3-ANCA and MPO-ANCA immunoassays for the diagnosis of ANCA-associated vasculitis (AAV) has raised doubts about the two-stage diagnostic strategy currently recommended for ANCA detection. OBJECTIVE: Presentation and discussion of the new international consensus recommendations on ANCA testing in AAV. METHODS: This article presents the new guidelines for ANCA testing that have been developed based on the results of a recent large multicenter study by the European Vasculitis Society (EUVAS). The draft of the author committee was revised by each contributor and subsequently distributed to 12 experts on 4 continents. After further revision the final document was returned for ratification and submitted for publication. RESULTS/CONCLUSION: The current study results confirm the superiority of the diagnostic value of antigen-specific immunoassays compared to IIF. The current consensus recommendations support the primary use of PR3-ANCA and MPO-ANCA immunoassays for diagnostic evaluation of patients with AAV without the categorical need for additional IIF.

[Current guidelines on ANCA-associated vasculitides : Common features and differences]. / Aktuelle Leitlinien zu ANCA-assoziierten Vaskulitiden : Gemeinsamkeiten und Unterschiede.

The results of a number of prospective randomized controlled clinical trials have led to changes in established strategies for the treatment of antineutrophil cytoplasmic antibody (ANCA) associated vasculitides (AAV) in recent years. Since 2014, a total of 4 scientific societies and study groups have systematically reviewed the new data and have formulated evidence-based recommendations for the management of AAV based on the analysis. These recommendations contain information on diagnosis, treatment (induction and maintenance), supportive care and monitoring of disease activity and resulting damage. This review compares the recently published recommendations of the German Society of Rheumatology (Deutschen Gesellschaft für Rheumatologie, DGRh), the European League Against Rheumatism (EULAR)/European Renal Association (ERA), the British Society of Rheumatology (BSR) and the Canadian Vasculitis Research Network (CanVasc). The comparative analysis reveals a high level of agreement on numerous topics but also shows some minor and even a few major differences in the respective recommended approach to diagnosis and treatment of AAV. Divergent recommendations predominantly exist in areas with little scientific evidence from clinical studies. Furthermore, some differences result from different interpretation of existing data or are influenced by characteristic features of the respective national healthcare system.

[Management of polymyalgia rheumatica and large vessel vasculitis]. / Management der Polymyalgia rheumatica und der Großgefäßvaskulitiden.

Imaging methods, such as joint and color duplex sonography, magnetic resonance imaging (MRI) and positron emission tomography (PET) nowadays facilitate the diagnosis of polymyalgia rheumatica and large vessel vasculitides and have now been included in the new classification criteria. In patients with typical symptoms, color duplex sonography of the temporal artery can replace a biopsy of the temporal artery for the diagnosis of giant cell arteritis (GCA); however, the role of these methods for patient follow-up and assessment of prognosis is unclear. Polymyalgia rheumatica is treated with glucocorticoids (GC) in an initial dosage of up to 20 mg per day. In patients with large vessel vasculitis higher doses are needed for induction of remission. Furthermore, the rate of relapse and GC-related adverse events are higher in GCA and Takayasu arteritis (TA). Thus, initial GC-sparing treatment with methotrexate or other immunosuppressants is recommended. Recent study data show an effectiveness of biologics. Recent data of the first placebo-controlled proof of concept trials showed that the interleukin-6 antagonist tocilizumab reduces GC requirements and relapse rates in patients with GCA and polymyalgia rheumatica. Both ustekinumab, a monocalonal antibody against interleukin-12/23p40 and the CTLA-4 immunoglobulin abatacept appeared to be effective in recent pilot trials for GCA. Antibodies against tumor necrosis factor alpha (TNF alpha) were ineffective for polymyalgia rheumatica and GCA in placebo-controlled trials but data from open label studies suggested some efficacy in refractory TA.