[Cardiovascular comorbidities in rheumatoid arthritis]. / Kardiovaskuläre Komorbiditäten bei rheumatoider Arthritis.

Approximately 80% of patients with rheumatoid arthritis (RA) suffer from comorbidities including more than 50% from cardiovascular (CV) diseases. Inflammatory activity is the main factor connecting RA with atherosclerosis, coronary heart disease, stroke, thromboembolic events and heart failure. Altogether these affect RA patients twice as frequently as the general population and CV events are the major cause of death in RA. Besides inflammatory activity, which can be reduced or eliminated by optimal treatment and controlling the RA activity, traditional CV risk factors also contribute to the total CV risk. These risk factors, such as hypertension, diabetes and hyperlipidemia can also be found more frequently in RA patients but often remain undetected and untreated for a long time. Reducing this deficit means improvement of the life expectancy for RA patients, which has been demonstrated in studies by treatment of hyperlipoproteinemia. Among the drugs used for RA treatment non-steroidal antirheumatic drugs and glucocorticoids increase the CV risk if used in the long term. Hydroxychloroquine, methotrexate and biologics on the other hand are able to dramatically reduce the risk. Elevated CV risks of inflammatory rheumatic diseases are widely unknown in primary care. Therefore, the rheumatologist should be responsible for assessment of risk factors but in real life motivation to do so is relatively low. Some studies could demonstrate that using nursing-based standardized assessment is an excellent opportunity to reduce these deficits. Depending on the individual risk reassessment should take place every 1-5 years.

[S2e guideline: treatment of rheumatoid arthritis with disease-modifying drugs]. / S2e-Leitlinie: Therapie der rheumatoiden Arthritis mit krankheitsmodifizierenden Medikamenten.

BACKGROUND: Medication-based strategies to treat rheumatoid arthritis are crucial in terms of outcome. They aim at preventing joint destruction, loss of function and disability by early and consistent inhibition of inflammatory processes. OBJECTIVE: Achieving consensus about evidence-based recommendations for the treatment of rheumatoid arthritis with disease-modifying anti-rheumatic drugs in Germany. METHODS: Following a systematic literature research, a structured process among expert rheumatologists was used to reach consensus. RESULTS: The results of the consensus process can be summed up in 6 overarching principles and 10 recommendations. There are several new issues compared to the version of 2012, such as differentiated adjustments to the therapeutic regime according to time point and extent of treatment response, the therapeutic goal of achieving remission as assessed by means of the simplified disease activity index (SDAI) as well as the potential use of targeted synthetic DMARDs (JAK inhibitors) and suggestions for a deescalating in case of achieving a sustained remission. Methotrexate still plays the central role at the beginning of the treatment and as a combination partner in the further treatment course. When treatment response to methotrexate is inadequate, either switching to or combining with another conventional synthetic DMARD is an option in the absence of unfavourable prognostic factors. Otherwise biologic or targeted synthetic DMARDs are recommended according to the algorithm. Rules for deescalating treatment with glucocorticoids and-where applicable-DMARDs give support for the management of patients who have reached a sustained remission. DISCUSSION: The new guidelines set up recommendations for RA treatment in accordance with the treat-to-target principle. Modern disease-modifying drugs, now including also JAK inhibitors, are available in an algorithm.

[Evidence-based recommendations for diagnostics and treatment of gouty arthritis in the specialist sector : S2e guidelines of the German Society of Rheumatology in cooperation with the AWMF]. / Evidenzbasierte Empfehlung zur Diagnostik und Therapie der Gichtarthritis im fachärztlichen Sektor : S2e-Leitlinie der Deutschen Gesellschaft für Rheumatologie (DGRh) in Kooperation mit der AWMF.

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.

Gustatory and olfactory function in patients with granulomatosis with polyangiitis (Wegener's).

OBJECTIVES: Recent findings suggest that autoimmune disorders predispose to a diminished capacity to taste and smell. This has been shown for patients with systemic lupus erythematosus as well as for patients with rheumatoid arthritis (RA). Granulomatosis with polyangiitis (GPA), with its particular manifestations in the upper respiratory tract, may therefore have an even higher impact on these senses. The aims of this study were to evaluate the gustatory and olfactory function in patients with GPA, to compare them to sex- and age-matched healthy controls, and to correlate these findings with their GPA disease severity. METHOD: Patients with established GPA were analysed by standardized assessments for gustatory and olfactory functions and examined for disease activity, stage of disease, and treatment. RESULTS: Forty-four GPA patients were tested for their chemosensory functions. Compared to age- and sex-matched healthy controls, GPA patients showed significantly decreased olfactory scores along with diminished scores for their gustatory functions. The diminished sense of smell in GPA patients correlated significantly with elevated C-reactive protein (CRP) values whereas the gustatory impairment correlated with the duration and extent of the disease. CONCLUSIONS: Our results indicate that olfactory and gustatory functions are significantly decreased in GPA. As the olfactory function of these patients was comparable to patients with RA, chemosensory impairment may not simply be a consequence of the involvement of the upper respiratory tract, but rather a common complication of systemic autoimmune diseases.

[Evidence-based recommendations for the management of undifferentiated peripheral inflammatory arthritis (UPIA). The German perspective on the international 3e initiative]. / Evidenzbasierte Empfehlungen zum Management einer undifferenzierten peripheren entzündlichen Arthritis (UPIA). Die deutsche Perspektive zur internationalen 3e-Initiative.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

[How early would we really administer biologics?]. / Wie früh würden wir Biologika wirklich einsetzen?

According to a survey carried out during the annual congress of the German Society for Rheumatology (DGRh) last year, many rheumatologists would like to initiate TNF-alpha inhibitors earlier than suggested in the EULAR recommendations. While most of the survey participants agreed with the initial MTX monotherapy favored therein, more than half would prefer to combine MTX with a biologic instead of a second DMARD after failure of this option. This decision seems to be based mainly on clinical experience. Although international therapy guidelines allow an earlier use of biologic therapy in special cases, particularly in Germany an extensive documentation and justification is needed for this treatment strategy. Future guidelines may allow several parallel drug sequences based on prognostic factors and individual biomarkers.

[German 2012 guidelines for the sequential medical treatment of rheumatoid arthritis. Adapted EULAR recommendations and updated treatment algorithm]. / S1-Leitlinie der DGRh zur sequenziellen medikamentösen Therapie der rheumatoiden Arthritis 2012. Adaptierte EULAR-Empfehlungen und aktualisierter Therapiealgorithmus.

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.

Rare monogenetic syndromes in rheumatology practice.

The EULAR Executive Committee defined eight overall objectives for EULAR to achieve by 2012. The first of these objectives is to strengthen activities in areas that are currently less prioritized, such as non-inflammatory and orphan diseases. This study aims to increase awareness of rheumatologists towards rare hereditary musculoskeletal disorders, by describing their genetics, pathogenesis, and typical clinical and radiological features. We analyzed patient charts from the recent 5 years from the Rheumatology Outpatient Department of the University Erlangen-Nuremberg and of two rheumatologic practices, all joined in a regional network ("Rheumazentrum Erlangen") retrospectively for hereditary musculoskeletal disorders other than hemochromatosis, autoinflammatory syndromes, lysosomal storage diseases, and hypermobility syndromes. We were able to identify four patients with trichorhinophalangeal syndrome type I, multiple exostoses, Kirner's deformity, and osteopoikilosis. In addition, a PubMed and OMIM ("Online Mendelian Inheritance in Man") database search was carried out using these as key words and all relevant articles were reviewed for each of these diseases. Our findings show that rare hereditary musculoskeletal disorders occur in a routine rheumatological setting and that rheumatologists should know the clinical and radiological features of these diseases in order to adequately counsel the patient.

Combination treatment with infliximab and leflunomide in patients with active rheumatoid arthritis: safety and efficacy in an open-label clinical trial.

OBJECTIVE: To assess the safety and efficacy of combination therapy with infliximab and leflunomide in adults with active rheumatoid arthritis (RA) despite leflunomide therapy. METHODS: Adult patients with active RA who had received leflunomide for at least 16 weeks were eligible for this 30-week, open-label trial. All patients received ongoing oral leflunomide (20 mg/day) and 3 mg/kg infliximab administered IV at weeks 0, 2, 6, 14, and 22. The primary end point was the percentage of patients with adverse events that led to patient withdrawal and were at least possibly related to treatment. Descriptive evaluations of efficacy and other safety assessments were performed. RESULTS: Twelve out of 70 patients (17.1%; upper 90% CI 24.5%) withdrew due to treatment-related adverse events. Adverse events were reported in 69 of 72 patients (95.8%); the most common were nasopharyngitis, diarrhea, and pruritus. Serious adverse events occurred in 16 out of 72 patients (22.2%). Significant improvements were observed in efficacy assessments, including Disease Activity Score 28 (DAS28) and pain. At end point, 19.4% of the patients showed a good improvement in DAS28 score and 46.3% had a moderate improvement. American College of Rheumatology (ACR) 20, 50, and 70 responses were achieved by 47.1%, 21.4%, and 12.9% of the patients, respectively. CONCLUSION: The combination of infliximab and leflunomide neither increased the rate of toxicities nor resulted in unexpected adverse events. Treatment-related withdrawals occurred at an acceptable frequency. Patients experienced clinically significant improvements. Treatment with infliximab plus leflunomide benefits the majority of patients, but monitoring of adverse events is required.

[Revision of the recommendations of the Commission on Pharmacotherapy of the German society for Rheumatology. Therapy with tumour necrosis factor blockers for inflammatory rheumatic illnesses]. / Neufassung der Empfehlungen der Kommission Pharmakotherapie der DGRh. Therapie mit Tumornekrosefaktor-hemmenden Wirkstoffen bei entzündlich-rheumatischen Erkrankungen.

Inflammatory rheumatic illnesses are associated with various types of pain as well as handicaps. The so called basic therapies are not sufficiently effective in many patients or are terminated due to side effects. This is where tumor necrosis factor blockers (TNF) can be used. In many cases, they lead to a substantial improvement of the symptoms, a reduction in disease related laboratory parameters, improvement in quality of life to stopping disease related damage when their effect is rapid. Common and severe side effects are few, although long-term data are still limited. The following contribution lists recommendations for the indications and symptomatology for the use of TNF blockers.

[Current therapeutic strategy for rheumatoid arthritis]. / Aktuelle Therapiestrategien bei rheumatoider Arthritis. Entzündung rasch beherrschen ist entscheidend für die Prognose.

The success of the treatment of rheumatoid arthritis depends primarily on early diagnosis. In most cases, basic therapy begins with methotrexate. Depending on the stage and course of the disease (radiographically detected early erosion and/or progression), basic immunosuppressive therapy can be combined or supplemented with cytokine antagonists. Furthermore, for specific indications, several alternative active substances (DMARD monotherapies) are available. Today the goal of therapy is always remission.

[Rheumatoid arthritis at the cervical spine -- an underestimated problem]. / Die rheumatoide Arthritis an der Halswirbelsäule: ein unterschätztes Problem.

BACKGROUND AND OBJECTIVE: The involvement of the cervical spine in rheumatoid arthritis can be essential regarding prognosis and mortality. The cervical myelopathy due to pannus formation and/or subluxation can be fatal. Aim of this study was to demonstrate the possible changes seen by MRI, and to establish a risk-profile for the individual patient. PATIENTS AND METHOD: Within a period of 24 months 214 patients with active RA were included. Clinical and laboratory data were obtained and plain radiographs of the cervical spine were taken. In patients with pathological findings on X-ray an MRI was performed (36 patients). RESULTS: Within the group of 214 patients 36 were identified to get an cervical spine MRI. In all cases the MRI showed significant changes: in 7 (19.5 %) pannus surrounded the dens, with additional erosions in one patient (2.7 %). In 25 (69.5 %) atlanto-axial-subluxation was present, 7 (19.5 %) showed a spondylodiscitis below C2. In 10 (27.8 %) a cervical myelopathy due to pannus or subluxation was present. There was no correlation of the MRI-results with symptoms and findings by examination. The patients with cervical spine disease were in all stages of RA. The majority was rheumatoid-factor positive. 5 out of 10 patients with cervical myelopathy showed neurological deficits: 3 patients died in consequence of neural compression, 2 patients underwent surgery successfully. CONCLUSION: The early detection of a cervical spine involvement in RA is essential to avoid possibly fatal complications. The only reliable method to achieve this goal has to include radiographic diagnostic including MRI of the cervical spine. Only this approach can answer the question of the right time-point for surgery. In daily clinical practice the cervical-spine involvement in RA is still underestimated.

[Glucocorticoid therapy in collagen diseases diseases]. / Glucocorticoidtherapie bei Kollagenosen.

Glucocorticoids are irreplaceable for the treatment of connective tissue diseases due to their strong and rapid anti-inflammatory and immuno-modulatory effects. Its use and their dosage depend on the activity of the disease and organ manifestations. There is no alternative to high doses, often even as intravenous pulse therapy, in life-threatening situations with imminent organ failure. Despite an additional immuno- suppressive medication, glucocorticosteroids are mandatory for long-term treatment in most cases. In special situations like high age, gravity or comorbidities like renal failure or hepatosis, glucocorticosteroids are the option with the least possible potential for complications. In the future, new corticosteroids and steroid sparing immuno-suppressants like biologics will be able to reduce the spectrum and the severity of corticoid-induced side effects. Modern state-of-the-art therapeutic regimens for patients with connective tissue diseases should not only be able to sufficiently control the disease activity but also include the prophylaxis of associated comorbidities like arteriosclerosis, osteoporosis or infections.

Interstitial granulomatous dermatitis with plaques and arthritis.

Interstitial granulomatous dermatitis and arthritis (IGDA) is a rare disease entity with female predominance. The case of a 53-year-old woman with erythemas, plaques and nodules associated with polyarthritis is presented. She was treated with cyclosporin A, with improvement of the joint affliction and complete clearance of skin lesions. The differential diagnosis of IGDA is discussed briefly.

[Relevance of a standardized staging study in patients with systemic vasculitis]. / Die Relevanz einer standardisierten Staging-Untersuchung bei Patienten mit systemischer Vaskulitis.

Primary systemic vasculitities play an important role in the differential diagnosis of systemic diseases. They can be classified according to newly developed classification criteria. In the past, systemic vasculitities were more diagnosed in the general phase of the disease. In the meantime limited forms can be diagnosed more easily. Prior to immunosuppressive therapy, a standardized staging-procedure is essential to define the extent of the disease. Therefore a program was established using methods that are easy to apply in all patients. In this setting the usefulness of this approach was investigated. Apart from the laboratory tests including antibody testing, the chest x-ray, consultation of the ENT specialist, ultrasound of the abdomen, and ECG were also very useful. The eye and neurological investigations, and the MRI of the head were of minor significance, but also important.

In vivo blockade of tumor necrosis factor-alpha in patients with rheumatoid arthritis: longterm effects after repeated infusion of chimeric monoclonal antibody cA2.

OBJECTIVE: To investigate the longterm consequences of tumor necrosis factor-alpha (TNF-alpha) blockade in patients with rheumatoid arthritis (RA), to compare changes after repeated infusion of cA2 monoclonal antibody with those occurring after the initial treatment, and to investigate significant correlations of cellular or serological changes to the duration of clinical benefit for each patient. METHODS: A clinical trial testing TNF-alpha monoclonal antibody cA2 in treatment of RA showed this therapeutic agent is highly effective. A dosage of 1 mg/kg or 10 mg/kg cA2, given in a single infusion, was compared to placebo. After clinical relapse all patients were (re)treated with 3 or 10 mg/kg cA2. In parallel to this clinical study, we investigated cellular and molecular changes induced by in vivo blockade of TNF-alpha. RESULTS: After an initial transient increase, T lymphocyte counts were not significantly different from starting values throughout the observation period. Monocyte counts as well as serum interleukin 6 (IL-6) and soluble intercellular adhesion molecule 1 (sICAM-1) concentrations remained decreased for several weeks after infusion. After a repeated infusion, increases in numbers of T cells and decreases in monocytes and IL-6 and sICAM-1 concentrations were evident again. Changes in cell counts, however, were smaller, especially in the group initially treated with the low dose (1 mg/kg), despite a higher retreatment dosage of 3 or 10 mg/kg cA2. Similarly, in this group decrease of IL-6 and sICAM-1 concentrations was less pronounced, was delayed to Day 7 after infusion, and lasted for a shorter period than seen after initial treatment. CONCLUSION: We conclude that in vivo TNF-alpha blockade leads to prolonged cellular and serological changes. This effect appears to be less pronounced after repeated infusion of cA2 compared to the initial treatment, mainly in the low dose group.

[Rare manifestation of large vessel vasculitis in systemic lupus erythematosus]. / Seltene Manifestation einer Grossgefässvaskulitis bei systemischem Lupus erythematodes.

Case-reports from two female patients with an occlusion of the right external iliac artery and femoral artery are presented due to a large-vessel vasculitis. Both patients suffered from systemic lupus erythematosus This rare manifestation occurred within the first few years of the disease and was important for prognosis and further treatment. Other manifestations of the disease were general symptoms and polyarthritis. In one case the vasculitis was confirmed by histology. A fibrous thickening of the intima and a vasculitis of small vessels within the adventitia were the prominent feature. This observation supports the idea of small vessel vasculitis as the characteristic manifestation in lupus erythematosus.