[Still's syndrome-similarities and differences between the juvenile and adult forms]. / Morbus Still ­ Ähnlichkeiten und Differenzen zwischen juveniler und adulter Form.

Still's syndrome includes systemic juvenile idiopathic arthritis (sJIA) and the adult form of Still's disease (adult-onset Still's disease, AOSD). Except for age, there are many similarities between sJIA and AOSD. A biphasic disease model is currently put forth. At disease onset, autoinflammation predominates, which is caused by dysregulation of the innate immune system. Later on, the disease can progress to a chronic-articular form, which is predominantly mediated by the adaptive immune system and is consequently due to autoimmunity. The "window-of-opportunity" hypothesis is based on this biphasic model and supports the assumption that an early, targeted therapy with cytokine blockade can prevent disease progression to chronic destructive arthritis. Macrophage activation syndrome (MAS) is a serious complication of the so-called cytokine storm during the systemic phase of the disease. Clinically, there are many similarities between sJIA and AOSD. Recurrent fever, a fleeting, salmon-colored rash, and arthralgia/arthritis are common signs and symptoms of both sJIA and AOSD. The few differences are mainly related to the therapies and their side effects in children versus adults. In addition, the contribution of genetics to pathogenesis is more pronounced in sJIA compared to AOSD, but there are also smooth transitions in this respect and both diseases are heavily influenced by exogenous factors such as microbial triggers. Future research aspects could include additional investigation of these triggers such as viruses, bacteria, or dysbiosis of the human microbiome.

Patients with fibromyalgia rarely fulfil classification criteria for axial spondyloarthritis.

Background: The Assessments of Spondyloarthritis international Society (ASAS) classification criteria for axial spondyloarthritis (axSpA) have been criticized because of insufficient differentiation towards FM. The aim of this study was to compare the performance of currently used classification criteria in patients diagnosed with axSpA or FM. Methods: Patients were prospectively included if diagnosed with axSpA or FM by the treating rheumatologist and evaluated by an independent examiner for fulfilment of the classification criteria for axSpA (ASAS criteria) and/or FM (1990 ACR classification and 2010 ACR diagnostic criteria). Patients with axSpA were stratified based on classification as non-radiographic axSpA (nr-axSpA) or AS. Symptom severity was assessed by established disease-related questionnaires. Results: Overall, 300 patients were included, 100 with FM and 200 with axSpA of which 100 each had nr-axSpA and AS. Almost all FM patients fulfilled the 2010 (100%) and 1990 ACR criteria (98%) for FM, but only 2% fulfilled the ASAS criteria. When calculations were based on only the FM patients with available HLA-B27 results (n = 40), the proportion fulfilling the ASAS criteria was 5%. All axSpA patients met the ASAS criteria but also the 2010 (24%) and 1990 (13.5%) FM criteria. More patients with AS (29% and 19%) than with nr-axSpA (19% and 8%) fulfilled the 2010 and 1990 FM criteria, respectively. Conclusion: FM patients only rarely fulfil classification criteria for axSpA but some axSpA patients also fulfil FM criteria. Since this was more frequent in patients with AS it may be related to the severity and duration of chronic pain in axSpA patients. Assessment instruments evaluated in axSpA are not disease-specific. The phenomenon of central pain sensitization in rheumatic diseases deserves more study.

2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis.

To update and integrate the recommendations for ankylosing spondylitis and the recommendations for the use of tumour necrosis factor inhibitors (TNFi) in axial spondyloarthritis (axSpA) into one set applicable to the full spectrum of patients with axSpA. Following the latest version of the European League Against Rheumatism (EULAR) Standardised Operating Procedures, two systematic literature reviews first collected the evidence regarding all treatment options (pharmacological and non-pharmacological) that were published since 2009. After a discussion of the results in the steering group and presentation to the task force, overarching principles and recommendations were formulated, and consensus was obtained by informal voting. A total of 5 overarching principles and 13 recommendations were agreed on. The first three recommendations deal with personalised medicine including treatment target and monitoring. Recommendation 4 covers non-pharmacological management. Recommendation 5 describes the central role of non-steroidal anti-inflammatory drugs (NSAIDs) as first-choice drug treatment. Recommendations 6-8 define the rather modest role of analgesics, and disprove glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs (DMARDs) for axSpA patents with predominant axial involvement. Recommendation 9 refers to biological DMARDs (bDMARDs) including TNFi and IL-17 inhibitors (IL-17i) for patients with high disease activity despite the use (or intolerance/contraindication) of at least two NSAIDs. In addition, they should either have an elevated C reactive protein and/or definite inflammation on MRI and/or radiographic evidence of sacroiliitis. Current practice is to start with a TNFi. Switching to another TNFi or an IL-17i is recommended in case TNFi fails (recommendation 10). Tapering, but not stopping a bDMARD, can be considered in patients in sustained remission (recommendation 11). The final two recommendations (12, 13) deal with surgery and spinal fractures. The 2016 Assessment of SpondyloArthritis international Society-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA.

Causes of pain in patients with axial spondyloarthritis.

Back pain, most frequently of the inflammatory type, is the leading symptom in patients with axial spondyloarthritis (axSpA). Back pain in these patients is usually either due to axial inflammation or structural changes based on new bone formation. However, there are other possible causes of pain in these patients. There is, for example, a strongly increased risk of vertebral fractures, and, especially in patients with longstanding disease, degenerative spinal changes may play an additional role as a cause of pain. Rarely, but rather specifically, patients with ankylosing spondylitis may develop subarachnoidal cysts that often cause neurologic symptoms, in extreme cases a cauda equina syndrome. It is therefore mandatory to always carefully evaluate the origin of back pain in these patients and to consider all possible differential diagnoses. The correct diagnosis is of major importance because treatments may differ considerably. In the monitoring of patients with axSpA it is especially important to consider that pain may have a different origin and it is crucial to notice changes in the nature of the reported back pain. Accordingly, the recently updated Assessment of Spondyloarthritis international Society (ASAS)/European League Against Rheumatism (EULAR) and the treat-to-target recommendations both define improvement of symptoms, a reduction of pain and abrogation of inflammation as important targets in axSpA that can be achieved by pharmacological and nonpharmacological treatments, in rare cases including surgical methods.

[Multi-Faceted Symptoms with Joint Pain, Exanthema and Eye Involvement]. / Facettenreiche Symptomatik mit Gelenkschmerzen, Exanthem und Augenbeteiligung.

HISTORY AND ADMISSION FINDINGS: In this case series, we describe 4 patients who presented to a rheumatologic clinic with very different complains however were ultimately diagnosed with the same underlying disease. The wide spectrum of symptoms included generalized maculopapular exanthema, arthralgia, myalgia and vision problems. One patient received anti-TNF therapy for ankylosing spondylitis and recurrent uveitis. On exam, joint swelling and skin changes were found. INVESTIGATION: All patients were found to have an elevated Treponema pallidum antibody titer and a positive of the rapid plasma reagin test. DIAGNOSIS: Patients were diagnosed with syphilis. TREATMENT AND COURSE: The first three patients received an intramuscular injection of 2.4 million benzabine penicillin G. The fourth patient was treated with penicillin 6 million IV 4 times a day for more than 14 days, due to immunosuppression CONCLUSION: In the presence of non-specific and often rather diffuse symptoms, with which patients in rheumatology often present, a non-primary rheumatological, e. g. infectious genesis, also needs to be considered. Due to the increasing incidence of syphilis in Germany in recent years special attention needs to be paid to this disease in rheumatological care.

The Role of Imaging in Diagnosing Axial Spondyloarthritis.

Imaging has a central role in the diagnosis, management, and follow-up of patients with axial spondyloarthritis (axSpA). For the early diagnosis of axSpA, magnetic resonance imaging is of utmost relevance. While no novel imaging techniques were developed during the past decade, improvements to the existing modalities have been introduced. This report provides an overview of the applications and limitations of the existing imaging modalities.

Efficacy and safety of biological and targeted-synthetic DMARDs: a systematic literature review informing the 2016 update of the ASAS/EULAR recommendations for the management of axial spondyloarthritis.

OBJECTIVES: To update the evidence for the efficacy and safety of (b)biological and (ts)targeted-synthetic disease-modifying anti-rheumatic drugs (DMARDs) in patients with axial spondyloarthritis (axSpA) to inform the 2016 update of the Assessment of SpondyloArthritis international Society/European League Against Rheumatism (ASAS/EULAR) recommendations for the management of axSpA. METHODS: Systematic literature review (2009-2016) for randomised controlled trials (RCT), including long-term extensions, strategy trials and observational studies (the latter was only for safety assessment and a comparator was required). Interventions were any bDMARD or tsDMARD. All relevant efficacy and safety outcomes were included. RESULTS: 76 papers and 24 abstracts fulfilled the inclusion criteria. Large treatment effects were found both in radiographic axSpA (r-axSpA) and non-radiographic axSpA (nr-axSpA) for all tumour necrosis factor inhibitors (TNFi) (NNT to achieve ASAS40 response ranged between 2.6-5.2 for r-axSpA and 2.3-5.4 for nr-axSpA). For nr-axSpA, efficacy was superior for those who had objective signs of inflammation (positive C reactive protein or inflammation on MRI-SI). Secukinumab 150 mg has shown efficacy in two phase 3 RCTs (NNT to achieve ASAS40 response: 3.4 and 4.0). Ustekinumab and tofacitinib have shown positive results in phase 2/proof-of-concept trials; trials with apremilast, rituximab, interleukin (IL)-6 antagonists and abatacept have failed their primary end points. New (unknown) safety signals were not found in the trials but long-term observational safety data for TNFi are still scarce. CONCLUSIONS: New evidence supports the efficacy and safety of TNFi both in r-axSpA and nr-axSpA. Secukinumab is the first drug targeting the IL-17 pathway in r-axSpA that has shown efficacy.

Efficacy and safety of non-pharmacological and non-biological pharmacological treatment: a systematic literature review informing the 2016 update of the ASAS/EULAR recommendations for the management of axial spondyloarthritis.

To assess the efficacy and safety of non-biological therapies in patients with axial spondyloarthritis (axSpA) to inform the update of the Assessment of SpondyloArthritis international Society (ASAS)/European League Against Rheumatism (EULAR) recommendations for the management of axSpA. A systematic literature review (2009-2016) of all non-pharmacological treatments, non-biological drugs (except targeted synthetic disease-modifying antirheumatic drugs (DMARDs)) and surgical therapies was performed. Randomised controlled trials (RCTs) and clinical controlled trials were assessed for efficacy and safety, while observational studies with a comparator were assessed for safety. All relevant efficacy and safety outcomes were included. Study heterogeneity precluded data pooling. If possible, Cohen's effect size was calculated for non-pharmacological treatments. In total, 45 papers and 2 abstracts were included. Studies on non-pharmacological treatments were very heterogeneous but overall confirmed a benefit for regular exercises, with small improvements in disease activity, function and spinal mobility. New studies on non-steroidal anti-inflammatory drugs (NSAIDs) confirmed their efficacy and new safety signals were not found. NSAIDs used continuously compared with on-demand did not reduce the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) mean change over 2 years in patients with ankylosing spondylitis with normal C reactive protein (CRP; ≤5 mg/L) (1 'negative' RCT (0.9 vs 0.8; p=0.62)), while for patients with high CRP, conflicting results were found (1 'positive' RCT (0.2 vs 1.7; p=0.003), 1 'negative' RCT (1.68 vs 0.96; p=0.28)). No new trials were found for conventional synthetic DMARDs (csDMARDs). Short-term high-dose systemic glucocorticoids showed limited efficacy. Regular exercises may improve several outcomes. Efficacy and safety of NSAIDs in axSpA are confirmed. Glucocorticoids are not proven to be effective in axSpA and new data on csDMARDs are lacking.

Monitoring ankylosing spondylitis: clinically useful markers and prediction of clinical outcomes.

Patient assessment in axial spondyloarthritis (axSpA) is multidimensional, and monitoring of disease activity, function and radiographic progression is complex. There is no simple 'gold standard' for measuring disease activity in all individual patients, as disease activity in axSpA is the sum of many different aspects and a complexity that cannot be represented by a single variable. Limited spinal mobility is a cardinal sign of ankylosing spondylitis and loss of spinal mobility has been reported to be a prognostic factor and most often evaluated with the Bath Ankylosing Spondylitis Functional Index. Imaging of the spine and assessment of safety aspects plays an important role in the monitoring of patients with axSpA. The timeframe for collecting information regarding disease activity, function and radiographic progression are recommended on an individual basis.