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The Systemic Lupus International Collaborating Clinics (SLICC), American College of Rheumatology (ACR), and the Lupus Foundation of America are developing a revised systemic lupus erythematosus (SLE) damage index (the SLICC/ACR Damage Index [SDI]). Shifts in the concept of damage in SLE have occurred with new insights into disease manifestations, diagnostics, and therapy. We evaluated contemporary constructs in SLE damage to inform development of the revised SDI.We conducted a 3-part qualitative study of international SLE experts. Facilitated small groups evaluated the construct underlying the concept of damage in SLE. A consensus meeting using nominal group technique was conducted to achieve agreement on aspects of the conceptual framework and scope of the revised damage index. The framework was finally reviewed and agreed upon by the entire group.Fifty participants from 13 countries were included. The 8 thematic clusters underlying the construct of SLE damage were purpose, items, weighting, reversibility, impact, time frame, attribution, and perspective. The revised SDI will be a discriminative index to measure morbidity in SLE, independent of activity or impact on the patient, and should be related to mortality. The SDI is primarily intended for research purposes and should take a life-course approach. Damage can occur before a diagnosis of SLE but should be attributable to SLE. Damage to an organ is irreversible, but the functional consequences on that organ may improve over time through physiological adaptation or treatment.We identified shifts in the paradigm of SLE damage and developed a unifying conceptual framework. These data form the groundwork for the next phases of SDI development.

Despite promising candidates for new therapeutic options in the treatment of systemic lupus erythematosus (SLE), many clinical trials have failed in the past few years. The disappointing results have been at least partly be attributed to trial designs. With the aim of stimulating new developments in SLE trial design, an international open space meeting was held on occasion of the European Lupus Meeting 2018 in Duesseldorf, Germany about ‘What are the topics you care about for making trials in lupus more effective?’. The Open Space is a participant-driven technology, where the discussion topics and schedule are selected during the meeting by all participants and discussion rounds are led by the people attending encouraging active contributions. Eleven topics were selected for further discussion, of which 6 were voted to be more intensively discussed in two consecutive rounds. Major topics were the optimal handling of glucocorticoids in clinical trials, the improvement of outcome measures, reducing or controlling the placebo response and the identification of biomarkers and stratification parameters. Further, the importance of local and international networks was emphasised. By networking, collaborations are facilitated, patient recruitment is more efficient and treatment can be harmonised thus lead to more successful SLE trials. Further discussions are needed to substantiate the results and develop new trial designs. The meeting was funded by the 'Rheumazentrum Rhein-Ruhr'

Pregnancy issues in patients with rheumatic diseases: the OB perspective for rheumatologists Learning Objectives: Understand the importance of pre pregnancy counselling for women with rheumatic disease in pregnancy Understand the risk factors for adverse pregnancy outcome in women with rheumatic disease Understand the medications which are compatible with use in pregnancy and lactation Understand the management of rheumatic disease in pregnancy Abstract: Rheumatic disease predominantly affects women of child-bearing age and are commonly encountered in obstetric practice. Pregnancy poses an important challenge for doctors looking after these women. Knowledge about medication safety, the effect of pregnancy on the disease, and vice versa, together with pre-conception counselling and multidisciplinary team care, are important to provide the best obstetric and medical care to these women. Women with rheumatic have increased risks of miscarriage, preterm delivery, pre-eclampsia, fetal growth restriction, and disease flare in pregnancy. The main risk factor for adverse pregnancy outcomes in inflammatory arthritides is active disease/flare. For women with SLE the risks are lupus nephritis, particularly with CKD class 3-5, anti Ro/La antibodies, active disease and antiphospholipid antibodies. The most important issues of delaying pregnancy until there is quiescent disease, ensuring continued remission by continuation of drugs that are safe in pregnancy and adequately and promptly treating any flare of disease will be discussed. Adequate surveillance of the mother and fetus is imperative, but stratification of women is important to ensure that those with low risk pregnancies are not over medicalized. There is an understandable reluctance to prescribe drugs, particularly immunosuppressant drugs, in pregnancy and in breast feeding mothers. However much harm can result if drugs are withdrawn, omitted or the dose reduced inappropriately. Active disease has an adverse effect on female fertility and time to pregnancy aw well as impacting adversely on pregnancy outcomes. Guidelines from the British Society of Rheumatology and EULAR have reviewed the safety data for antirheumatic drugs in pregnancy. These publications include recommendations for which drugs are compatible with pregnancy and during lactation. These guidelines should reduce errors of omission where important medication for disease control are discontinued prior to or in pregnancy and empower rheumatologists to help women to time their pregnancies during disease remission and with continuation of medications including biologics compatible with pregnancy. References: [1] Ateka-Barrutia O, Nelson-Piercy C. Connective tissue disease in pregnancy. Clin Med. 2013; 13: 580-4. Soh MC, Nelson-Piercy C. High-risk pregnancy and the rheumatologist. Rheumatology (Oxford). 2015 Apr;54(4):572-87. doi: 10.1093/rheumatology/keu394. Epub 2014 Dec 3. [2] Flint J, Panchal S, Hurrell A, van de Venne M, Gayed M, Schreiber K, Arthanari S, Cunningham J, Flanders L, Moore L, Crossley A, Purushotham N, Desai A, Piper M, Nisar M, Khamashta M, Williams D, Gordon C, Giles I; BSR and BHPR Standards, Guidelines and Audit Working Group. BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding-Part I: standard and biologic disease modifying anti-rheumatic drugs and corticosteroids. Part II: analgesics and other drugs used in rheumatology practice. Rheumatology (Oxford). 2016 Jan 10. pii: kev405. [3] Gotestam Skorpen C, Hoeltzenbein M, Tincani A, Fischer-Betz R, Elefant E, Chambers C, da Silva J, Nelson-Piercy C, Cetin I, Costedoat-Chalumeau N, Dolhain R, Forger F, Khamashta M, Ruiz-Irastorza G, Zink A, Vencovsky J, Cutolo M, Caeyers N, Zumbuhl C, Ostensen M. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis. 2016 May;75(5):795-810. doi: 10.1136/annrheumdis-2015-208840. Epub 2016 Feb 17. Disclosure of Interests: Catherine Nelson-Piercy Consultant for: UCB, Speakers bureau: UCB

Background:Macrophage activation syndrome (MAS) is a potentially fatal complication of systemic lupus erythematosus (SLE).(1) Overlapping clinical features of SLE activity with MA makes it a clinical diagnosis. There is limited data from developing countries like India.Objectives:To study the clinical features, treatment, and outcomes in SLE-MAS.Methods:This single-centre, retrospective study included patients fulfilling SLICC 2011 criteria for SLE, admitted from January 2017 to November 2019, and diagnosed as MAS by a team of attending physicians. Their demographic and clinical data, treatment, and outcomes were recorded. H score and SLEDAI were calculated. Patients were assessed for HLH classification criteria (2004) and preliminary diagnostic criteria for MAS in childhood SLE (cSLE).Results:Sixteen patients (median age – 26 years, 15 females) were included. Twelve patients (75%) had MAS as the initial presentation of SLE. The common clinical features were fever (100%) and cytopenias (100%). The mean duration of symptoms was 60 days. The most frequent biochemical abnormalities were high ferritin (>500 ng/ml, 100%) and elevated transaminases (100%, aspartate transaminase > alanine transaminase). Common complications were renal (43.8%), neurological (43.8%), and coagulopathy (43.8%). Seven and 16 patients fulfilled the HLH 2004 and cSLE – MAS preliminary criteria, respectively. The median H score was 222, giving a cumulative probability of 96%. All the patients received high-dose steroids. Cyclophosphamide pulse and cyclosporine were administered to 8 (50%) and 6 (37.5%) patients respectively. There were four (25%) in-hospital mortalities.CharacteristicN=16Age (years)26 (19.5 – 30)Duration of symptoms (days)60 (18.7 – 90)Fever16 (100)Pancreatitis1 (6.3)Renal7 (43.8)Neurological7 (43.8)Myocarditis6 (37.5)Hepatomegaly7 (43.8)Splenomegaly3 (18.8)Lymphadenopathy12 (75)Anaemia16 (100)Leukopenia13 (82)Thrombocytopenia14 (88.2)Coagulopathy7 (43.8)Concomitant infection3 (18.8)H score222 (193 – 254)cSLE-MAS diagnostic criteria16 (100%)HLH 2004 (≥5)7 (43.8)Corticosteroids16 (100%)Cyclophosphamide8 (50%)Intravenous immunoglobulin2 (12.5%)Cyclosporine6 (37.5%)Death4 (25%)All data presented as n (%) and median (IQR)cSLE-MAS – Childhood systemic lupus erythematosus – Macrophage activation syndrome, HLH – Hemophagocytic lymphohistiocytosisParameterN = 16Haemoglobin (g/dL)6.9 (5.7 – 7.8)Total leucocyte count (cells/mm3)1400 (1025 -3175)3 (18.8)1000 – 25009 (56.3)2500 - 40001 (6.3)Platelet (cells/mm3)57500 (23500 – 95250)3 (18.8)20000 – 500003 (18.8)50000 – 1 lac8 (50)Serum ferritin > 500 ng/ml16 (100%)Fibrinogen2.48 (1.6 – 4)Triglycerides (mg/dL)375 (294 -470)AST/ALT (U/L)153 (113 – 234) / 90 (68 – 170)Procalcitonin (pg/mL)0.8 (0.3 – 1.4)Lactate dehydrogenase (U/L)1674 (1081 – 2184)Erythrocyte sedimentation rate (mm in 1sthour)61 (44 – 69)C- reactive protein (mg/L)36 (6.3 – 52)Bone marrow examination14 (87.5)Increased histiocytes with hemophagocytosis5 (32.5)All data presented as n (%) and median (IQR)ALT – Alanine transaminase, AST – Aspartate transaminaseConclusion:Fever, cytopenia, high ferritin, and elevation of transaminases were the commonest features in this series of SLE-MAS. SLE-MAS carried a high mortality (25%) despite aggressive treatment.References:[1]Gavand P-E, Serio I, Arnaud L, Costedoat-Chalumeau N, Carvelli J, Dossier A, et al. Clinical spectrum and therapeutic management of systemic lupus erythematosus-associated macrophage activation syndrome: A study of 103 episodes in 89 adult patients. Autoimmun Rev. 2017;16(7):743–9.Acknowledgments:NONEDisclosure of Interests:None declared

Background:There is very limited information about the passage of biologics into breast milk and into the peripheral blood of breastfed infants. However, based on pharmacological properties of biologic DMARDs (bDMARDs) lactation may not be discouraged in patients with chronic inflammatory rheumatic disease to treat or prevent postpartum relapses. We here report two cases treated with bDMARDs during lactation: one woman with Muckle-Wells syndrome (MWS) treated with canakinumab and one woman with microscopic polyangiitis (MPA) treated with rituximab.Objectives:To determine the level of rituximab and canakinumab in breast milk, in sera of breastfed infants as well as in sera of the mother and to calculate the average daily infant dose and the relative infant dose.Methods:Serum and milk levels of Rituximab were measured by ELISA using commercially available coating and detection antibodies. For Canakinumab an ELISA was established by coating of plates with recombinant human IL-1beta and detection of Canakinumab in samples by a polyclonal anti-human IgG coupled to HRP. In both cases separate standard curves for serum and milk were established. Serum samples and milk samples of unexposed healthy controls were used to determine the lower limit of quantification.Results:One patient with MWS received canakinumab 150 mg s.c. to treat a worsening of her disease ten days postpartum. She continued to breastfeed her child. The average concentration of canakinumab in milk samples collected on 10 consecutive days was 15.8 ng/ml. The average daily infant dose was 0.002 mg/kg/day. The relative infant dose, which refers infant to maternal exposure on a dose/weight basis, was 0.11%. There was no detectable canakinumab in the serum of the infant.One patient with MPA received rituximab 500 mg i.v. as a remission maintenance therapy four months postpartum. She continued to breastfeed her child. The average concentration of rituximab in milk samples collected on 4 consecutive days was 3.71 ng/ml. The average daily infant dose was 0.001 mg/kg/day. The relative infant dose was 0.01%. There was no detectable rituximab in the serum of the infant.Conclusion:Only minimal concentrations of canakinumab and rituximab can be detected in breastmilk. For both bDMARDs, the relative infant dose was below 1% of the maternal dose, which is considered unlikely to be of clinical concern. The lack of detectable levels of canakinumab and rituximab in the infants’ sera supports the notion of low oral bioavailability of large monoclonal antibodies. Together, the results are similar to those seen in TNF inhibitors which are regarded to be compatible with breastfeeding, yet more data are needed (1, 2, 3).References:[1]Götestam Skorpen C, Hoeltzenbein M, Tincani A, Fischer-Betz R, Elefant E, Chambers C, da Silva J, Nelson-Piercy C, Cetin I, Costedoat-Chalumeau N, Dolhain R, Förger F, Khamashta M, Ruiz-Irastorza G, Zink A, Vencovsky J, Cutolo M, Caeyers N, Zumbühl C, Østensen M. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis. 2016 May;75(5):795-810. doi: 10.1136/annrheumdis-2015-208840. Epub 2016 Feb 17.[2]Clowse ME, Förger F, Hwang C, Thorp J, Dolhain RJ, van Tubergen A, Shaughnessy L, Simpson J, Teil M, Toublanc N, Wang M, Hale TW. Minimal to no transfer of certolizumab pegol into breast milk: results from CRADLE, a prospective, postmarketing, multicentre, pharmacokinetic study. Ann Rheum Dis. 2017 Nov;76(11):1890-1896. doi: 10.1136/annrheumdis-2017-211384. Epub 2017 Aug 16.[3]Matro R, Martin CF, Wolf D, Shah SA, Mahadevan U. Exposure Concentrations of Infants Breastfed by Women Receiving Biologic Therapies for Inflammatory Bowel Diseases and Effects of Breastfeeding on Infections and Development.Gastroenterology. 2018;155(3):696–704. doi:10.1053/j.gastro.2018.05.040Disclosure of Interests:Astrid Zbinden: None declared, Klara Eriksson: None declared, Frauke Förger Grant/research support from: Unrestricted grant from UCB, Consultant of: UCB, GSK, Roche, Speakers bureau: UCB, GSK

Background Cardiac involvement is present in 7% to 35% of patients with rheumatoid arthritis (RA). Anecdotal case series have associated the use of antimalarial drugs with the presence of electrocardiographic disturbances in patients with RA Objectives To assess whether the use of antimalarial drugs is associated with the presence of electrocardiographic abnormalities in RA patients. The main clinical associations were also evaluated Methods A single-centre, case-control (1:1 proportion) medical chart review study was performed. A total of 144 patients with RA (ACR/EULAR 2010 criteria) were studied, and grouped as follows: 72 with a history of antimalarial drug use (case) and 72 who never used antimalarial drugs (control). We excluded individuals with a history of ischaemic heart disease or an already diagnosed disturbance of the cardiac rhythm/conduction. Results A total of 37 cases of electrocardiographic disturbances were found in patients receiving antimalarials (51%), but only 18 cases (25%) in the control group (p=0.001), giving an odds ratio (OR) of 3.17 (95% CI, 1.57 to 6.42). Rhythm disturbances observed in the antimalarial group were: left anterior branch hemiblock (n=12, 32.4%), right branch block (n=10; 27.02%), 1st degree AV block (n=5; 13.5%), bifascicular block (n=4; 10.8%), posterior hemiblock of the left branch (n=3; 8.1%), incomplete left bundle branch block (n=2, 5.4%), and left bundle branch block (n=1, 2.7%). Right bundle branch block was the only statistically significant conduction disorder (27.02% vs 5.5%with p value of 0.004 [OR 11.45 1.43–92]). The average dose of hydroxychloroquine was 3.02±0.41 mg/kg, while the dose of chloroquine was 2.23±0.13 mg/kg). A history of prednisone consumption also was associated with an increased risk to present an electrical cardiac disturbance (p=0.005; OR 9.73, from 2.00 to 47.32). Conclusions In this study, the use of antimalarial drugs was associated with an increased risk to present disturbances of the cardiac rhythm/conduction in patients with established RA. References [1] Seferovic PM, et al. Cardiac arrhythmias and conduction disturbances in autoimmune rheumatic diseases. Rheumatology (Oxford)2006;45:iv39–42. [2] Coskun S, et al. Cardiac involvement in patients with rheumatoid arthritis. Journal of Rheumatology2005;8:23–31. [3] Costedoat-Chalumeau N, et al. Heart conduction disorders related to antimalarials toxicity: an analysis of electrocardiograms in 85 patients treated with hydroxychloroquine for connective tissue diseases. Rheumatology2007;46:808–810. Disclosure of Interest None declared

Background Hydroxychloroquine (HCQ) are considered to be effective against cutaneous lupus erythematosus (CLE) and symptoms associated with systemic lupus erythematosus (SLE) such as rashes, joint pain, and fatigue. In a randomized controlled trial in stable active patients with SLE on HCQ treatment, those who achieved blood HCQ levels greater than or equal to 1000ng/ml had a tendency for reduced SLE flares during a 7 month period [1]. To prevent ocular toxicity, HCQ should be maintained at a dose of 6.5mg/kg or less for ideal body weight [2], however, optimal HCQ dosage is unclear. Objectives To extract the problem of the dosage based on ideal body weight and identify safer and more effective HCQ dosage. Methods We enrolled patients who took HCQ for SLE or CLE more than 3 months in our institute and 2 related facilities from September 2015. We used Cutaneous Lupus Erythematous Disease Area and Severity Index (CLASI) to evaluate cutaneous symptoms and evaluated effect at start of administration and 3 months of that. The attending doctors assessed the adverse events (AEs). We investigated the change of serum biomarker, such as the value of serum complement and anti-ds-DNA body, the number of white blood cells, lymphocytes and platelets. Results We enrolled the 30 patients with administration of HCQ more than 3 months and in CLE were 2 cases, in SLE were 28 cases. In 21 cases HCQ dosage were based on ideal weight. The AEs were in 13/30 cases (43.3%). The AEs were the new cutaneous symptoms in 5 cases, eye manifestation in 3 cases (abnormal visual field in 2 cases, color anomaly in 1 case), diarrhea in 2 cases, fever in 2 cases, feeling of fatigue in 2 cases, renal dysfunction in 1 case, muscular pain in 1 case, and pericarditis in 1 case. The eye manifestation in the 3 cases disappeared for a few days by stopping or reducing HCQ dosage. Although we needed glucocorticoid treatment for pericarditis, the other AEs improved by reducing HCQ dosage or stopping. The AEs of taking HCQ 200mg/day were in 6 cases, 200mg and 400mg alternatively on every other day in 6 cases, and 400mg/day in 1 case. The AEs of taking HCQ dosage based on ideal body weight were in 10/21 cases (47.6%) and by minimal dosage in 3/9 cases (33.3%). 22/28 cases (78.6%) significant improved cutaneous symptoms (amount of mean change of CLASI -4.57, p=0.024). There is no difference in the efficacy of cutaneous symptoms between group received HCQ based on ideal body weight (80.0%) and the others (92.3%). 5/21 cases of HCQ based on ideal body weight were made to reduce HCQ dosage due to AEs, but all 5 cases improved cutaneous symptoms. 53.3% (16/30) cases increased complement, but other biomarkers didn9t change. Conclusions HCQ was effective for the treatment of CLE even when HCQ dosage was reduced due to AEs. These findings suggest that low-dose HCQ is also effective and safe, and HCQ initial dosage wasn9t the need to adjust for ideal body weight. References Costedoat-Chalumeau N, et al. Hydroxychloroquine in systemic lupus erythematosus: results of a French multicentre controlled trial (PLUS Study). Ann Rheum Dis. 2013;72(11):1786–92. Ronald B. Melles, Michael F.Marmor. The risk of toxic retinopathy in patients on long-term hydroxychloroquine therapy. JAMA Ophthalmol. 2014;132(12):1453–60. Disclosure of Interest None declared

© 2016 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.Systemic lupus erythematosus (SLE; OMIM 152700) is a genetically complex autoimmune disease. Genome-wide association studies (GWASs) have identified more than 50 loci as robustly associated with the disease in single ancestries, but genome-wide transancestral studies have not been conducted. We combined three GWAS data sets from Chinese (1,659 cases and 3,398 controls) and European (4,036 cases and 6,959 controls) populations. A meta-analysis of these studies showed that over half of the published SLE genetic associations are present in both populations. A replication study in Chinese (3,043 cases and 5,074 controls) and European (2,643 cases and 9,032 controls) subjects found ten previously unreported SLE loci. Our study provides further evidence that the majority of genetic risk polymorphisms for SLE are contained within the same regions across both populations. Furthermore, a comparison of risk allele frequencies and genetic risk scores suggested that the increased prevalence of SLE in non-Europeans (including Asians) has a genetic basis.

ObjectivesDevelop recommendations for women's health issues and family planning in systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS).MethodsSystematic review of evidence followed by modified Delphi method to compile questions, elicit expert opinions and reach consensus.ResultsFamily planning should be discussed as early as possible after diagnosis. Most women can have successful pregnancies and measures can be taken to reduce the risks of adverse maternal or fetal outcomes. Risk stratification includes disease activity, autoantibody profile, previous vascular and pregnancy morbidity, hypertension and the use of drugs (emphasis on benefits from hydroxychloroquine and antiplatelets/anticoagulants). Hormonal contraception and menopause replacement therapy can be used in patients with stable/inactive disease and low risk of thrombosis. Fertility preservation with gonadotropin-releasing hormone analogues should be considered prior to the use of alkylating agents. Assisted reproduction techniques can be safely used in patients with stable/inactive disease; patients with positive antiphospholipid antibodies/APS should receive anticoagulation and/or low-dose aspirin. Assessment of disease activity, renal function and serological markers is important for diagnosing disease flares and monitoring for obstetrical adverse outcomes. Fetal monitoring includes Doppler ultrasonography and fetal biometry, particularly in the third trimester, to screen for placental insufficiency and small for gestational age fetuses. Screening for gynaecological malignancies is similar to the general population, with increased vigilance for cervical premalignant lesions if exposed to immunosuppressive drugs. Human papillomavirus immunisation can be used in women with stable/inactive disease.ConclusionsRecommendations for women's health issues in SLE and/or APS were developed using an evidence-based approach followed by expert consensus.

Due to the rarity of relapsing polychondritis (RP), many unmet needs remain in the management of RP. Here, we present a systematic review of clinical practice guidelines (CPGs) published for RP, as well as a list of the most striking unmet needs for this rare disease. We carried out a systematic search in PubMed and Embase based on controlled terms (medical subject headings and Emtree) and keywords of the disease and publication type (CPGs). The systematic literature review identified 20 citations, among which no CPGs could be identified. We identified 11 main areas with unmet needs in the field of RP: the diagnosis strategy for RP; the therapeutic management of RP; the management of pregnancy in RP; the management of the disease in specific age groups (for instance in paediatric-onset RP); the evaluation of adherence to treatment; the follow-up of patients with RP, including the frequency of screening for the potential complications and the optimal imaging tools for each involved region; perioperative and anaesthetic management (due to tracheal involvement); risk of neoplasms in RP, including haematological malignancies; the prevention and management of infections; tools for assessment of disease activity and damage; and patient-reported outcomes and quality of life indicators. Patients and physicians should work together within the frame of the ReCONNET network to derive valuable evidence for obtaining literature-informed CPGs.