ObjectiveTo analyse the impact of the COVID-19 pandemic on rheumatic patients’ and rheumatologists’ usage, preferences and perception of digital health applications (DHAs).MethodsA web-based national survey was developed by the Working Group Young Rheumatology of the German Society for Rheumatology and the German League against Rheumatism. The prospective survey was distributed via social media (Twitter, Instagram and Facebook), QR code and email. Descriptive statistics were calculated, and regression analyses were performed to show correlations.ResultsWe analysed the responses of 299 patients and 129 rheumatologists. Most patients (74%) and rheumatologists (76%) believed that DHAs are useful in the management of rheumatic and musculoskeletal diseases (RMDs) and felt confident in their own usage thereof (90%; 86%). 38% of patients and 71% of rheumatologists reported that their attitude had changed positively towards DHAs and that their usage had increased due to COVID-19 (29%; 48%). The majority in both groups agreed on implementing virtual visits for follow-up appointments in stable disease conditions. The most reported advantages of DHAs were usage independent of time and place (76.6%; 77.5%). The main barriers were a lack of information on suitable, available DHAs (58.5%; 41.9%), poor usability (42.1% of patients) and a lack of evidence supporting the effectiveness of DHAs (23.2% of rheumatologists). Only a minority (<10% in both groups) believed that digitalisation has a negative impact on the patient–doctor relationship.ConclusionThe COVID-19 pandemic instigated an increase in patients’ and rheumatologists’ acceptance and usage of DHAs, possibly introducing a permanent paradigm shift in the management of RMDs.

Objective Mepolizumab proved to be an efficacious treatment for eosinophilic granulomatosis with polyangiitis (EGPA) at a dose of 300 mg every 4 weeks in the randomized, controlled MIRRA trial. In a few recently reported studies, successful real‐life experiences with the approved dose for treating severe eosinophilic asthma (100 mg every 4 weeks) were observed. We undertook this study to assess the effectiveness and safety of mepolizumab 100 mg every 4 weeks and 300 mg every 4 weeks in a large European EGPA cohort. Methods We included all patients with EGPA treated with mepolizumab at the recruiting centers in 2015–2020. Treatment response was evaluated from 3 months to 24 months after initiation of mepolizumab. Complete response to treatment was defined as no disease activity (Birmingham Vasculitis Activity Score [BVAS] = 0) and a prednisolone or prednisone dose (or equivalent) of ≤4 mg/day. Respiratory outcomes included asthma and ear, nose, and throat (ENT) exacerbations. Results Two hundred three patients, of whom 191 received a stable dose of mepolizumab (158 received 100 mg every 4 weeks and 33 received 300 mg every 4 weeks) were included. Twenty‐five patients (12.3%) had a complete response to treatment at 3 months. Complete response rates increased to 30.4% and 35.7% at 12 months and 24 months, respectively, and rates were comparable between mepolizumab 100 mg every 4 weeks and 300 mg every 4 weeks. Mepolizumab led to a significant reduction in BVAS score, prednisone dose, and eosinophil counts from 3 months to 24 months, with no significant differences observed between 100 mg every 4 weeks and 300 mg every 4 weeks. Eighty‐two patients (40.4%) experienced asthma exacerbations (57 of 158 [36%] who received 100 mg every 4 weeks; 17 of 33 [52%] who received 300 mg every 4 weeks), and 31 patients (15.3%) experienced ENT exacerbations. Forty‐four patients (21.7%) experienced adverse events (AEs), most of which were nonserious AEs (38 of 44). Conclusion Mepolizumab at both 100 mg every 4 weeks and 300 mg every 4 weeks is effective for the treatment of EGPA. The 2 doses should be compared in the setting of a controlled trial.

The histaminergic neurons in the tuberomamillary nucleus (TMN) of the posterior hypothalamus are involved in the control of arousal. These neurons are sensitive to hypercapnia as has been shown in experiments examining c-Fos expression, a marker for increased neuronal activity. We investigated the mechanisms through which TMN neurons respond to changes in extracellular levels of acid/CO2. Recordings in rat brain slices revealed that acidification within the physiological range (pH from 7.4 to 7.0), as well as ammonium chloride (5 mM), excite histaminergic neurons. This excitation is significantly reduced by antagonists of type I metabotropic glutamate receptors and abolished by benzamil, an antagonist of acid-sensing ion channels (ASICs) and Na+/Ca2+ exchanger, or by ouabain which blocks Na+/K+ ATPase. We detected variable combinations of 4 known types of ASICs in single TMN neurons, and observed activation of ASICs in single dissociated TMN neurons only at pH lower than 7.0. Thus, glutamate, which is known to be released by glial cells and orexinergic neurons, amplifies the acid/CO2-induced activation of TMN neurons. This amplification demands the coordinated function of metabotropic glutamate receptors, Na+/Ca2+ exchanger and Na+/K+ ATPase. We also developed a novel HDC-Cre transgenic reporter mouse line in which histaminergic TMN neurons can be visualized. In contrast to the rat, the mouse histaminergic neurons lacked the pH 7.0-induced excitation and displayed only a minimal response to the mGluR I agonist DHPG (0.5 μM). On the other hand, ammonium-induced excitation was similar in mouse and rat. These results are relevant for the understanding of the neuronal mechanisms controlling acid/CO2-induced arousal in hepatic encephalopathy and obstructive sleep apnoea. Moreover, the new HDC-Cre mouse model will be a useful tool for studying the physiological and pathophysiological roles of the histaminergic system.

Objective Despite increased physician’s awareness and improved diagnostic and serological testing in the recent years, the interval between the initial symptoms and the diagnosis of Systemic lupus erythematosus (SLE) is still very long. Our aim was to study this delay and its association to the outcome of the disease. Methods Information on demographics, onset of first symptoms, first physicians visit and time of diagnosis was assessed by self-reported questionnaires among SLE patients in Germany (LuLa cohort, n = 585) in the year 2012. Disease activity (Systemic Lupus Activity Questionnaire; SLAQ), disease related damage (Brief Index of Lupus Damage; BILD), health related quality of life (Short Form 12) and fatigue (FSS) were chosen as proxies for outcome. Linear regression analysis was used to analyze the association of the delay in diagnosis to the outcome, adjusted for age, disease duration and sex. Results Mean duration between the onset of symptoms and the diagnosis of SLE was 47 months (SD 73). The longer the time to diagnosis, the higher the disease activity (β = 0.199, p < 0.0001), the disease-related damage (β = 0.137, p = 0.002) and fatigue (β 0.145, p = 0.003) and the lower the health-related quality of life (physical β = −0.136, p = 0.004, mental β = −0.143, p = 0.004). Conclusion In systemic lupus erythematosus, longer time to diagnosis was associated with worse outcome. Concepts in care with the intention to shorten the time to diagnosis are needed to improve the long-term outcome of the disease.

A few decades ago, the therapy goal of patients with systemic lupus erythematosus (SLE) was survival and the prevention of organ failure. Today, clinical remission and low disease activity are believed to be the optimal therapeutic targets. These aims are difficult to reach for many patients, but they still do not address the health-related quality of life (QoL) that is significantly impaired in SLE patients. Even in the state of remission, QoL and fatigue are insufficient controlled. Thus, patient-oriented research is essential to design new strategies for the management of lupus patients. The INTEGRATE project analyses the patients’ and physicians’ perspectives to pave the way to design an innovative therapeutic strategy for lupus and focuses on the multifaceted dimensions of the disease burden. Shared decision making (SDM) could include the patient’s perspective of SLE to treatment strategy and consider QoL and the burden of lupus into the process of therapy decision.