Sjögren's Syndrome (SS) as a member of the systemic connective tissue diseases comprises a complex of symptoms which occur alone or in the context of other rheumatic conditions. In view of multiple overlapping features the classification in a primary and secondary form in SS is a simplification which renders diagnosis and categorization sometimes more difficult than easier. Diagnosis of an SS/SLE-overlap is not the consequence of diagnostic uncertainty but of the distinct presentation of a particular, related complex of symptoms. However, only if this differentiation is followed by proper diagnostic or therapeutic implications the clinical problem of SS will be dealt with all aspects. For example, confusion of primary SS with rheumatoid arthritis leading to a treatment with gold salts might have disastrous consequences and a markedly elevated ESR must not cast suspicion of malignancy or infection or even be treated "ex juvantibus" if it is due to the typical hypergammaglobullinaemia in a patient with SS.

Confusion

10.1055/s-2008-1043586

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2027 Continuous twice-a-day radiotherapy and concomitant CDDP-5fu chemotherapy (BiRCF) for the treatment of locallyadvanced inoperable pharyngeal carcinomas: Final results of a multicentric phase II study (FNCLCC)

International Journal of Radiation Oncology*Biology*Physics (1995)

R.J. Bensadoun Patrick Chauvel O. Dassonville Yves Laudoyer S. Bourdin

Concomitant

10.1016/0360-3016(95)97931-p

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Methyl donor micronutrients, CD40-ligand methylation and disease activity in systemic lupus erythematosus: A cross-sectional association study

Lupus (2021)

Stefan Vordenbäumen Alexander Sokolowski Anna Rosenbaum Claudia Gebhard Johanna Raithel

Hypomethylation of CD40-ligand (CD40L) in T-cells is associated with increased disease activity in systemic lupus erythematosus (SLE). We therefore investigated possible associations of dietary methyl donors and products with CD40L methylation status in SLE.Food frequency questionnaires were employed to calculate methyl donor micronutrients in 61 female SLE patients (age 45.7 ± 12.0 years, disease duration 16.2 ± 8.4 years) and compared to methylation levels of previously identified key DNA methylation sites (CpG17 and CpG22) within CD40L promotor of T-cells using quantitative DNA methylation analysis on the EpiTYPER mass spectrometry platform. Disease activity was assessed by SLE Disease Activity Index (SLEDAI). Linear regression modelling was used. P values were adjusted according to Benjamini & Hochberg.Amongst the micronutrients assessed (g per day), methionine and cysteine were associated with methylation of CpG17 (β = 5.0 (95%CI: 0.6-9.4), p = 0.04; and β = 2.4 (0.6-4.1), p = 0.02, respectively). Methionine, choline, and cysteine were additionally associated with the mean methylation of the entire CD40L (β = 9.5 (1.0-18.0), p = 0.04; β = 1.6 (0.4-3.0), p = 0.04; and β = 4.3 (0.9-7.7), p = 0.02, respectively). Associations of the SLEDAI with hypomethylation were confirmed for CpG17 (β=-32.6 (-60.6 to -4.6), p = 0.04) and CpG22 (β=-38.3 (-61.2 to -15.4), p = 0.004), but not the mean methylation of CD40L. Dietary products with the highest impact on methylation included meat, ice cream, white bread, and cooked potatoes.Dietary methyl donors may influence DNA methylation levels and thereby disease activity in SLE.

Choline

10.1177/09612033211034559

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Metacarpophalangeal Joints in Rheumatoid Arthritis: Delayed Gadolinium-enhanced MR Imaging of Cartilage—A Feasibility Study

Radiology (2010)

Falk Miese Benedikt Ostendorf Hans‐Jörg Wittsack D Reichelt Tallal C. Mamisch

To evaluate the feasibility of delayed gadolinium-enhanced magnetic resonance (MR) imaging of the cartilage of metacarpophalangeal (MCP) joints in patients with rheumatoid arthritis (RA) compared with that in control subjects.Institutional review board approval and informed consent were obtained. Thirty-one MCP joints in 10 patients with RA (mean age, 59 years; range, 35-77 years) and six healthy volunteers (mean age, 51 years; range, 30-71 years) were examined with delayed gadolinium-enhanced MR imaging of cartilage. Sagittal images of the second and third MCP joints (hereafter, MCP II and MCP III) were acquired with a three-dimensional dual-flip-angle gradient-echo sequence at 3.0 T. B(1) field inhomogeneity-corrected T1 maps were calculated, and delayed gadolinium-enhanced MR imaging of cartilage values for phalangeal and metacarpal cartilage were determined. In addition, cartilage thickness was measured. A nonparametric Mann-Whitney U test was used to assess differences between groups.Phalangeal and metacarpal delayed gadolinium-enhanced MR imaging of cartilage values in patients with RA (MCP II: 388 msec ± 105 [standard deviation] and 342 msec ± 79, respectively; MCP III: 409 msec ± 96 and 371 msec ± 89, respectively) were significantly lower than in control subjects (MCP II: 598 msec ± 62 and 560 msec ± 51, respectively; MCP III: 586 msec ± 57 and 561 msec ± 80, respectively). Cartilage thickness of both joints was comparable in patients with RA (MCP II: 1.28 mm ± 0.50, MCP III: 1.17 mm ± 0.24) and control subjects (MCP II: 1.42 mm ± 0.33, MCP III: 1.18 mm ± 0.26).Delayed gadolinium-enhanced MR imaging of cartilage of the MCP joints is feasible at 3.0 T. Delayed gadolinium-enhanced MR imaging of cartilage may help to assess cartilage degeneration in morphologically normal-appearing MCP II and III cartilage in patients with RA.

Metacarpophalangeal joint

Flip angle

10.1148/radiol.10100459

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AB0633 Measuring what matters to lupus patients: translating patient views into novel patient-reported outcomes

Annals of the Rheumatic Diseases (2018)

Sophie Cleanthous Antoine Regnault M. Schneider Caroline Gordon Susan J. Bartlett

Background

The 2010 U.S. FDA guidance¹ on systemic lupus erythematosus (SLE) acknowledged that 'improvements in clinical outcome measures in patients with SLE may not always translate to improvements in how patients feel or function' and encourages the use of patient-reported outcome instruments (PROs) to assess changes in outcomes that matter most to patients. Fatigue, identified by patients as their chief complaint during the Lupus Patient-Focused Drug Development (PFDD) meeting², is not optimally measured by existing PROs¹. There is a need for new patient-centred outcome measures as they are pivotal to PFDD. To address this, UCB has been conducting a multi-faceted, patient-centric, mixed methods research programme including evidence generated from >2100 SLE patients.

Objectives

There were three main objectives of the programme: 1) identify what concepts are most important to measure for SLE patients when evaluating treatment benefit; 2) critically evaluate the extent to which these concepts are captured by existing PROs; and 3) explore the opportunity to develop and evaluate new conceptually-based PROs in SLE.

Methods

There were three stages: 1) development of a preliminary treatment benefit conceptual model related to SLE including disease symptoms and impacts (generated from literature review, and patient and clinician input); 2) formal comparison of i) the conceptual model and the content validity (qualitative review) of existing SLE PROs and ii) psychometric properties (ie. SF-36, FACIT-F, and LupusQoL in the discontinued EMBODY Phase 3 studies for epratuzumab); 3) development of new conceptually-based PROs in SLE (figure 1).

Results

A preliminary treatment benefit conceptual model in SLE was developed. Among the many symptoms and disease impacts reported by SLE patients, physical fatigue, mental fatigue ('brain fog'), sudden fatigability, joint/muscle stiffness and pain, skin symptoms and mobility difficulties featured as most troublesome. The content validity of 10 widely used PROs was found to be limited when compared to this conceptual model. Psychometric analysis (based on Rasch Measurement Theory) confirmed the limitations of the SLE PROs used in the EMBODY studies and suggested post-hoc reconceptualisation would improve the ability of the scales to detect clinical change. This led to the development of five new conceptually-based SLE PROs (ie. fatigue, pain, mobility, symptom severity, and emotional state), which are currently being explored in >500 SLE patients in a Phase 2b dapirolizumab pegol study (NCT02804763) and two cross-sectional, non-interventional, observational studies. Data on the new PROs are currently being assessed at several sites in the USA, Latin America, UK and Germany and will be available in the coming months.

Conclusions

New, well-defined and reliable PROs to better capture the patient perceptions of the symptoms and impact of SLE are needed. UCB has developed five new PROs which offer the promise of improved patient-centred outcome measurements in SLE and other autoimmune diseases.

References

[1] Food and Drug Administration. Guidance for Industry. Systemic Lupus Erythematosus. June 2010. [2] Lupus Patient-Focused Drug Development meeting, 25 September 2017.

Disclosure of Interest

S. Cleanthous Employee of: Modus Outcomes Ltd, A. Regnault Employee of: Modus Outcomes Ltd, M. Schneider Consultant for: UCB Pharma, C. Gordon Grant/research support from: UCB Pharma, Consultant for: UCB, Merck Serono, GSK, S. Bartlett: None declared, S. Cano Shareholder of: Modus Outcomes Ltd, Employee of: Modus Outcomes Ltd, T. Morel Shareholder of: UCB Pharma, Employee of: UCB Pharma

10.1136/annrheumdis-2018-eular.5435

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Sjögren’s syndrome: state of the art on clinical practice guidelines

RMD Open (2018)

Vasco C. Romão Rosaria Talarico Carlo Alberto Scirè Ana Vieira Tobias Alexander

Sjögren’s syndrome (SS) is a complex autoimmune rheumatic disease that specifically targets salivary and lachrymal glands. As such, patients typically had ocular and oral dryness and salivary gland swelling. Moreover, skin, nasal and vaginal dryness are frequently present. In addition to dryness, musculoskeletal pain and fatigue are the hallmarks of this disease and constitute the classic symptom triad presented by the vast majority of patients. Up to 30% to 50 % of patients with SS may present systemic disease; moreover, there is an increased risk for the development of non-Hodgkin’s lymphoma that occurs in a minority of patients. The present work was developed in the framework of the European Reference Network (ERN) dedicated to Rare and Complex Connective Tissue and Musculoskeletal Diseases (ReCONNET). In line with its goals of aiming to improve early diagnosis, treatment and care of rare connective and musculoskeletal diseases, ERN-ReCONNET set to review the current state of clinical practice guidelines (CPGs) in the rare and complex connective tissue diseases of interest of the network. Therefore, the present work was aimed at providing a state of the art of CPGs for SS.

10.1136/rmdopen-2018-000789

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Knochendichte und 25-OH-Vitamin-D- Serumspiegel bei Patienten mit systemischem Lupus erythematodes

Zeitschrift für Rheumatologie (2001)

Andréa Becker Rebecca S. B. Fischer M. Schneider

Bone remodeling

10.1007/s003930170035

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Citations (36)