2019 update of the EULAR recommendations for the management of systemic lupus erythematosus.

Our objective was to update the EULAR recommendations for the management of systemic lupus erythematosus (SLE), based on emerging new evidence. We performed a systematic literature review (01/2007-12/2017), followed by modified Delphi method, to form questions, elicit expert opinions and reach consensus. Treatment in SLE aims at remission or low disease activity and prevention of flares. Hydroxychloroquine is recommended in all patients with lupus, at a dose not exceeding 5 mg/kg real body weight. During chronic maintenance treatment, glucocorticoids (GC) should be minimised to less than 7.5 mg/day (prednisone equivalent) and, when possible, withdrawn. Appropriate initiation of immunomodulatory agents (methotrexate, azathioprine, mycophenolate) can expedite the tapering/discontinuation of GC. In persistently active or flaring extrarenal disease, add-on belimumab should be considered; rituximab (RTX) may be considered in organ-threatening, refractory disease. Updated specific recommendations are also provided for cutaneous, neuropsychiatric, haematological and renal disease. Patients with SLE should be assessed for their antiphospholipid antibody status, infectious and cardiovascular diseases risk profile and preventative strategies be tailored accordingly. The updated recommendations provide physicians and patients with updated consensus guidance on the management of SLE, combining evidence-base and expert-opinion.

The existential experience of everyday life with systemic lupus erythematosus.

AIM: To explore from the perspective of women the nature of basic existential conditions while living with systemic lupus erythematosus. BACKGROUND: Systemic lupus erythematosus has an unpredictable disease course and is documented to cause an existential rearrangement of life. The significance of changes in existential conditions and related experiences are unclear in the context of nursing and women with systemic lupus erythematosus. DESIGN: A qualitative design guided by Van Manen's hermeneutic-phenomenological methodology. METHOD: Individual in-depth interviews with 15 women diagnosed with systemic lupus erythematosus and of various ages, disease durations and severities were undertaken from September 2013 - October 2015. Data were analysed following van Manen's phenomenological approach and using drawing as an interpretive tool. FINDINGS: The main existential experience was interpreted as a person "moving with the waves of systemic lupus erythematosus" constituted by the themes "oscillating between presence and absence of systemic lupus erythematosus," "recognizing space and bodily possibilities and limitations" and "being enriched through relationships and activities." When systemic lupus erythematosus was flaring, well-being was threatened and a laborious time to escape the feeling of a setback-in-life persisted long after the disease was medically under control. CONCLUSION: Daily life with systemic lupus erythematosus is conditioned by a prominent need to be in existential motion, related to the absence and presence of systemic lupus erythematosus. The experience of a setback-in-life by illness might challenge well-being and indicates that periods of disease flares or disturbing symptoms are critical time points to provide support.

Being in a standstill-of-life: women's experience of being diagnosed with systemic lupus erythematosus: a hermeneutic-phenomenological study.

Systemic lupus erythematosus (SLE) is a highly unpredictable and potentially lethal disease which ultimately challenges identity, future and the meaning of life. In a caring context, the experience of good health is perceived to be a balance between biomedical health and the existential experience of having a good life. This balance is jeopardised in the face of severe chronic illness and leads to extensive suffering if not handled carefully. Research suggests that patients suffering from severe chronic illness need support on an existential level, but also emphasises that, given its elusive nature, caring for the existential dimension is difficult to manage. This paper explores the experience of being diagnosed with SLE as an existential phenomenon. Through repeated phenomenological and hermeneutic interviews with 15 women conducted from 2013 to 2015, data concerning the diagnostic phase of SLE were analysed using Van Manen's phenomenology of practice. The essence was found to be a standstill in life comprehended through three inter-related themes: standing in a swirl of events, standing on uneven ground and standing at a turning point with oneself and others. The paper elucidates how existential life phenomena are lived, during the course of being diagnosed. In conclusion, it provides an ethical awareness of how a standstill in life is lived and of the patients' existential transition during the diagnostic phase. A holistic approach is recommended in caring for patients with SLE.

Rapid infusion with rituximab: short term safety in systemic autoimmune diseases.

To describe the incidence, types and severity of adverse events, related to an accelerated regime of rituximab infusion in patients with various autoimmune diseases. Fifty-four patients with systemic autoimmune disease, to be treated with 1,000 mg of rituximab twice 2 weeks apart, participated. Pre-medication (oral prednisolone, anti-histamine and paracetamol) was administered 1-4 h before infusion start. The first infusion was administered over a period of 195 min. The second infusion over a period of 90 min. Any adverse events were classified using the Clinical Trials Classification of Adverse Events (CTCAE) v. 3.0. Ten patients (18.5%) experienced at least one infusion-related reaction (IRR) ever. The first infusion was associated with reactions in 4 CTCAE categories of which rhinitis were the most frequent. The CTCAE severity grading showed six patients (11.1%) had a grade 1 reaction. One patient (1.8%) had grade 2 events on both infusions and two patients (3.6%) had a grade 3 event on both infusions. RA patients more often had an infusion-related reaction (IRR) (9.2%) than the rest. The types of IRR were mostly of allergic or angio-oedematic nature. In practise, the rapid infusion was an easy to use regime and the second infusion is of time sparing significance to health professionals. No unexpected side effects were observed in relation to the accelerated regime.

Qualitative factors shaping MS patients' experiences of infusible disease-modifying drugs: a critical incident technique analysis.

OBJECTIVE: To explore factors shaping the experiences of patients with relapsing-remitting multiple sclerosis with infusible disease-modifying drugs in a hospital setting. DESIGN AND SETTINGS: The critical incident technique served as a framework for collecting and analysing patients' qualitative account practices involving infusible disease-modifying drugs. Data were collected through semistructured interviews and one single-case study. Participants were recruited from all five regions in Denmark. Inductive thematic analysis was used to identify and interpret factors shaping patients' infusion journey over time. PARTICIPANTS: Twenty-two patients with relapsing-remitting multiple sclerosis receiving infusion with disease-modifying drugs (natalizumab, alemtuzumab and ocrelizumab). RESULTS: Four time scenarios-preinfusion, day of infusion, long-term infusion and switch of infusion-associated with the infusion of disease-modifying drugs were analysed to reveal how different factors could both positively and negatively affect patient experience. Time taken to make the treatment decision was affected by participants' subjective perceptions of their disease activity; this may have set off a treatment dilemma in the event of a pressing need for treatment. Planning and routine made infusion practices manageable, but external and internal surroundings, including infusion room ambience and the quality of relationships with healthcare professionals and fellow patients, affected patients' cognitive state and well-being irrespective of the infusion regimen. Switching the infusion regimen can reactivate worries akin to the preinfusion scenario. CONCLUSION: This study provides novel insight into the positive and negative factors that shape patients' experience of infusion care practices. From a patient's perspective, an infusion practice is not a solitary event in time but includes planning and routine which become an integral part of their multiple sclerosis management. The quality of space and the ambience of the infusion room, combined with the relationship with healthcare professionals and fellow patients, can be a significant source of knowledge and support people with relapsing-remitting multiple sclerosis in their experience of agency in life.

EBNA1 IgM-Based Discrimination Between Rheumatoid Arthritis Patients, Systemic Lupus Erythematosus Patients and Healthy Controls.

Epstein-Barr Virus (EBV) has been associated with development of rheumatic connective tissue diseases like rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in genetically susceptible individuals. Diagnosis of RA and SLE relies on clinical criteria in combination with the presence of characteristic autoantibodies. In addition, antibodies to several EBV antigens have been shown to be elevated in patients with these diseases compared to healthy controls (HC). Here, we elaborated improved enzyme-linked immunosorbent assays for antibodies (IgM, IgA, IgG) to the EBV proteins Epstein-Barr Virus nuclear antigen (EBNA)1 and early antigen diffuse (EAD) in order to determine their potential diagnostic role. We showed that especially EBNA1 IgM distinguished RA from SLE and HCs and also distinguished SLE from HCs. EBNA1 IgA was almost as effective in differentiating RA from SLE and HC, while EAD IgG and IgA were able to discern SLE patients from RA patients and HCs. Collectively, these findings illustrate the potential diagnostic use of antibodies to EBV proteins to diagnose RA and to differentiate SLE from RA.

Immune responses to an early lytic cytomegalovirus antigen in systemic lupus erythematosus patients: T-cell responses, cytokine secretions and antibody status.

We investigated immune responses to a lytic cytomegalovirus antigen (CMVpp52), and to a lytic human herpes virus (HHV) 6 antigen (HHV6p41), in systemic lupus erythematosus (SLE) patients and healthy controls (HCs), in order to clarify if the previously established impaired responses to Epstein-Barr virus (EBV) in SLE patients is a general defect in their responses against (all) HHVs. Multiplex Luminex technology results showed a normal induction of five quantified cytokines (interferon γ, interleukin(IL)12, IL17, IL10, and tumor necrosis factor α) in SLE patients compared to HCs upon stimulation with CMVpp52 and HHV6p41. However, flow cytometric results showed a reduced upregulation of the activation marker CD69 on T-cells from SLE patients (n = 17) compared to HCs (n = 17) upon stimulation with CMVpp52, indicating limited or defective CMVpp52-specific T-cells and/or poor antigen-presentation in SLE patients, and thereby possibly decreased control of the CMV infection. In conclusion, the dysfunctional immune response against EBV previously established in SLE patients does not seem to apply to the same degree regarding the immune responses against CMV or HHV6. Results designate that the main contributing HHV agent in development or exacerbation of SLE (in genetically predisposed individuals) is the previously determined uncontrolled EBV infection, and to a lesser extent CMV infection, and probably with no involvement of HHV6 infection.

Impaired Cytokine Responses to Epstein-Barr Virus Antigens in Systemic Lupus Erythematosus Patients.

We analyzed cytokine responses against latent and lytic Epstein-Barr virus (EBV) antigens in systemic lupus erythematosus (SLE) patients and healthy controls (HCs) to obtain an overview of the distinctive immune regulatory response in SLE patients and to expand the previously determined impaired EBV-directed T-cell response. The concentrations of 14 cytokines (IL2, IL4, IL5, IL6, IL10, IL12, IL17, IL18, IL1ß, IFNγ, TNFα, TNFß, TGFß, and GM-CSF) were quantified upon stimulation of whole blood with latent state antigen EBNA1, lytic cycle antigen EBV-EA/D, and the superantigen SEB. To avoid results affected by lack of lymphocytes, we focused on SLE patients with normal levels. Decreased induction of IL12, IFNγ, IL17, and IL6 upon EBNA1 stimulation and that of IFNγ, IL6, TNFß, IL1ß, and GM-CSF upon EBV-EA/D stimulation were detected in SLE patients compared to HCs. IFNγ responses, especially, were shown to be reduced. Induction of several cytokines was furthermore impaired in SLE patients upon SEB stimulation, but no difference was observed in basic levels. Results substantiate the previously proposed impaired regulation of the immune response against latent and lytic cycle EBV infection in SLE patients without lymphopenia. Furthermore, results indicate general dysfunction of leukocytes and their cytokine regulations in SLE patients.

Variation in nestmate recognition ability among polymorphic leaf-cutting ant workers.

A key feature for the success of social insects is division of labour, allowing colony members to specialize on different tasks. Nest defence is a defining task for social insects since it is crucial for colony integrity. A particularly impressive and well-known case of worker specialization in complex hymenopteran societies is found in leaf-cutting ants of the genera Atta and Acromyrmex. We hypothesized that three morphological worker castes of Acromyrmex echinatior differ in their likelihood to attack intruders, and show that major workers are more aggressive towards non-nestmate workers than medium and minor workers. Moreover, minors do not discriminate between nestmate and non-nestmate brood, while larger workers do. We further show that A. echinatior ants use cuticular chemical compounds for nestmate recognition. We took advantage of the natural variation in the cuticular compounds between colonies to investigate the proximate factors that may have led to the observed caste differences in aggression. We infer that major workers differ from medium workers in their general propensity to attack intruders (the "action component" of the nestmate recognition system), while minors seem to be less sensitive to foreign odours ("perception component"). Our results highlight the importance of proximate mechanisms underlying social insect behaviour, and encourage an appreciation of intra-colony variation when analysing colony-level traits such as nest defence.

Reduced response to Epstein-Barr virus antigens by T-cells in systemic lupus erythematosus patients.

OBJECTIVE: Epstein-Barr virus (EBV) has for long been associated with systemic lupus erythematosus (SLE). In this study, we investigated the levels of latent and lytic antigen EBV-specific T-cells and antibodies in SLE patients. METHODS: T cells were analyzed by flow cytometry and antibodies were analyzed by enzyme-linked immunosorbent assay. RESULTS: SLE patients showed a significantly reduced number of activated (CD69) T-cells upon ex vivo stimulation with EBV nuclear antigen (EBNA) 1 or EBV early antigen diffuse (EBV-EA/D) in whole blood samples compared with healthy controls. Also, a reduced number of T-cells from SLE patients were found to produce interferon-γ upon stimulation with these antigens. Importantly, responses to a superantigen were normal in SLE patients. Compared with healthy controls, SLE patients had fewer EBV-specific T-cells but higher titres of antibodies against EBV. Furthermore, an inverse correlation was revealed between the number of lytic antigen EBV-specific T-cells and disease activity of the SLE patients, with high-activity SLE patients having fewer T-cells than low-activity SLE patients. CONCLUSIONS: These results indicate a limited or a defective EBV-specific T-cell response in SLE patients, which may suggest poor control of EBV infection in SLE with an immune reaction shift towards a humoral response in an attempt to control viral reactivation. A role for decreased control of EBV as a contributing agent in the development or exacerbation of SLE is proposed.

Effect of the TNF-α inhibitor adalimumab in patients with recalcitrant sarcoidosis: a prospective observational study using FDG-PET.

BACKGROUND: Tumour necrosis factor-alpha (TNF-α) plays a crucial role in sarcoidosis. In severe disease, treatment with TNF-α inhibitors may be effective. OBJECTIVES: Changes in sarcoid disease activity were assessed by fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) in patients with recalcitrant sarcoidosis treated with adalimumab. METHODS: Prospective 24-week observational study. Patients continued medication with steroids and antimetabolites and received adalimumab 40 mg subcutaneously every other week. Ten patients with biopsy-proven sarcoidosis (two men) were included with a median age of 47 years (range 35-73). An FDG-PET showing uptake indicating sarcoid activity was required at inclusion and repeated at the end of the study. FDG-PET uptake was assessed by calculated standardised uptake value (SUV). Blood samples and lung function tests were performed regularly. Quality of life was assessed by the short-form health survey (SF-36) questionnaire. RESULTS: Following treatment with adalimumab, FDG-PET uptake decreased in nine patients (P = 0.011) and increased in one patient. Maximum SUV fell from median 14.1 to 7.0 (P < 0.03), and mean SUV fell from median 6.5 to 2.9 (P < 0.02). Six patients had uptake in the lungs, which decreased after treatment (P = 0.035). Six patients had uptake in the lymph nodes, which decreased after treatment in five patients (P = 0.035). Four patients had non-lymphatic extrathoracic uptake, which decreased after treatment (P = 0.05). There was no effect of adalimumab on pulmonary function tests, serum angiotensin I converting enzyme and blood lymphocyte (CD3+, CD4+, CD8+) concentrations. Physical component summary score (SF-36) increased during treatment, mental component summary score was unchanged. CONCLUSION: In sarcoidosis, treatment with adalimumab can reduce disease activity, as assessed by FDG-PET.