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Background:Systemic sclerosis (SSc) is a multiorgan disease, that frequently affects the skin and involves the lung in up to 70 percent of cases with a 10 years mortality rate in SSc up to 50 percent. B cell-depleting therapy with rituximab (RTX) seems to be effective in the treatment of SSc, but data from randomized controlled trials (RCTs) are missing and there is no consensus on frequency and dosage of RTX in SSc. [1-3]Objectives:We aimed to assess the long-term efficacy and safety of quarterly administered RTX in SSc.Methods:Retrospective analyses of 40 consecutive systemic sclerosis patients suffering from interstitial lung disease and progredient skin involvement treated with rituximab twice within 14 days every three months from 2010-2020. Of RTX-treated patients 42.5 % were treated with RTX monotherapy and 47.5 with RTX in combination with other immunosuppressants. The patients’ fulfilled the LeRoy and the ACR/EULAR Criteria for SSc. (4) Modified Rodnan skin score (mRSS), lung function test results, laboratory values including serum immunoglobulin (IgG, IgA, IgM) concentrations.[5] The clinical parameters are included in the EScSGAI and have been documented over time.[6] (Figure 1)Results:In total 40 SSc patients received RTX as described above over a median time of 3.9 years (1-10 years). A significant improvement in median mRSS (baseline: 19, month 24: 16, p<0.001), as well as a stable predicted forced vital capacity (FVC) were observed from baseline to month 24. There were no new or unexpected safety signals especially regarding treatment-related infectious adverse events. Immunoglobuline concentrations stayed within the normal range and specific antibodies to pneumococcal polysaccharides were preserved despite of long term B cell depleting therapy. During the observation period of up to ten years none of the patients died.(A) European Scleroderma Study Group Activity Index, (B) modified Rodnan Skin Score (mRss), (C) forced vital capacity (FVC) in percent predicted, and (D) diffusing lung capacity of carbonmonoxide (DLCO) in percent during RTX treatment. The number of patients treated is indicated by n, the duration of treatment on the x-axis by months. Median + 95%CI Significance was calculated using paired Wilcoxon Test.Conclusion:Conclusion: SSc can be effectively and safely treated by 3-monthly, low-dose RTX. Controlled, randomized studies are needed to validate the advantage of continuous B cell depletion by 3-monthly low dose RTX application compared to other application intervals.REFERENCES:[1] Katsumoto TR, Whitfield ML, Connolly MK. The pathogenesis of systemic sclerosis. Annu Rev Pathol. 2011 Feb 28;6:509–37.[2] Moazedi-Fuerst FC, Kielhauser SM, Brickmann K, Hermann J, Lutfi A, Meilinger M, et al. Rituximab for systemic sclerosis: arrest of pulmonary disease progression in five cases. Results of a lower dosage and shorter interval regimen. Scand J Rheumatol [Internet]. 2014 Jan [cited 2015 Feb 25];43(3):2.[3] Maher TM, Tudor VA, Saunders P, Gibbons MA, Fletcher S V, Denton CP, et al. Rituximab versus intravenous cyclophosphamide in patients with connective tissue disease-associated interstitial lung disease in the UK (RECITAL): a double-blind, double-dummy, randomised, controlled, phase 2b trial. Lancet Respir Med. 2022 Jan;[4] van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, et al. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum [Internet]. 2013 Nov [cited 2016 Mar 23];65(11):2737–47.[5] Venhoff N, Effelsberg NM, Salzer U, Warnatz K, Peter HH, Lebrecht D, et al. Impact of rituximab on immunoglobulin concentrations and B cell numbers after cyclophosphamide treatment in patients with ANCA-associated vasculitides. PLoS One. 2012 May 21;7(5).[6] Valentini G, Bencivelli W, Bombardieri S, D’Angelo S, Della Rossa A, Silman AJ, et al. European Scleroderma Study Group to define disease activity criteria for systemic sclerosis. III. Assessment of the construct validity of the preliminary activity criteria. Ann Rheum Dis [Internet]. 2003 Sep [cited 2018 Oct 10];62(9):901–3.Acknowledgements:NIL.Disclosure of Interests:None declared.

Objective: To correlate the number of chondrocytes in healthy and osteoarthritic human articular cartilage with age, and to evaluate the influence of donor age on total proteoglycan synthesis. Methods: Chondrocytes were isolated from human articular cartilage derived from hip joints with and without osteoarthritic lesions. The cell number was normalised to cartilage sample wet weight. In addition, the influence of age on chondrocyte numbers was assessed histomorphometrically. Chondrocytes were grown as monolayer cultures for seven days in a chemically defined serum-free basal medium. Total proteoglycan synthesis was measured by [35S]sulphate incorporation into newly synthesised macromolecules. Results: Chondrocyte numbers in healthy cartilage decreased significantly with advancing age (r = −0.69, p<0.0001). In contrast to healthy specimens, chondrocyte numbers were decreased in osteoarthritic cartilage irrespective of and unrelated to age, and differed markedly, by an average of 38%, from the cell numbers found in healthy individuals (p<0.0001). Regarding synthesis of matrix macromolecules, no dependence on patients’ age, either in healthy or in osteoarthritic specimens, could be observed. Conclusions: Under the experimental conditions employed, chondrocytes from healthy and osteoarthritic joints synthesised comparable amounts of cartilage macromolecules, independent of age or underlying osteoarthritic disease. Thus the decrease in chondrocyte number in aging and osteoarthritic joints could be a crucial factor in limiting tissue replenishment.

Drug-induced hepatotoxicity is a frequent cause of liverdisease and acute liver failure, particularly in patients treatedwith multiple drugs. Several antibacterial drugs have thepotential to cause severe liver injury and failure. This articleaims to increase the awareness and understanding of druginducedliver injury (DILI) due to antibacterial drugs. Itreviews the pattern of antibacterial DILI and provides detailson molecular mechanisms and toxicogenomics, as well asclinical data based on epidemiology studies. Certain antibacterialdrugs are more frequently linked to hepatotoxicity thanothers. Therefore, the hepatotoxic potential of tetracyclines,sulfonamides, tuberculostatic agents, macrolides, quinolones,and beta-lactams are discussed in more detail. Efforts toimprove the early detection of DILI and the acquisition ofhigh-quality epidemiological data are pivotal for increasedpatient safety.

BackgroundPatients with primary Sjögren Syndrome (PSS) are affected by glandular and extraglandular manifestations leading to physical and mental impairment. How these factors affect the health related quality of life (HRQL) of these patients is largely unexplored.ObjectivesThis qualitative study was conducted to investigate patients' perspectives and needs influencing HRQL in PSS.MethodsWe recruited 20 consecutive PSS patients fulfilling the American-European consensus classification criteria out of the PSS cohort of the Medical University Graz, Austria. A total of 6 focus group sessions were performed. A discussion guide with four open-ended questions was developed containing all elementary components of HRQL (physical, mental, social, daily life). All interviews were audio-recorded and transcribed verbatim. A modified meaning condensation procedure was used to analyse the data.ResultsAll patients were female, the mean age was 61 (SD ±8) years and mean disease duration was 5 (±2) years. The focus group sessions took on average 58 ±13 minutes. The number of patients in each group ranged from three to four.The interview analysis resulted in 484 meaning units, 254 subconcepts and 87 concepts. The identified concepts were grouped into three dimensions: physical dimension, psychological & emotional challenges and social life & daily living. An inter-dependency of the three dimensions was identified.The concepts most commonly reported belonged to the physical dimension: pain, dryness and complaints related to these two symptoms. Patients frequently mentioned consequences of dryness including recurrent inflammation of eyes and ears, loss of sense of smell and taste, sleeping disturbances and the inability to eat and chew.In the dimension psychological & emotional challenges, the most frequently mentioned concepts were “being worried about the future”, “a long symptom to diagnosis lag” and “the feeling of being an encumbrance for their families”. Concepts like dependency on relatives in daily life, difficulties at work and financial burden were classified within the dimension of social life & daily living.ConclusionsWe found that three interrelated dimensions (physical dimension, psychological & emotional challenges and social life & daily living) best reflected patients' experiences and feelings related to PSS. HRQL in PSS patients was influenced not only by dryness rather psychological and social burden clearly impacted the patients.Disclosure of InterestNone declared

Objective: To analyse the effects of rigorous immunoglobulin removal by immunoadsorption (IAS) on proteinuria (primary outcome variable), disease activity (SIS, SLEDAI, ECLAM), and autoantibodies to double stranded DNA (anti-dsDNA) in active systemic lupus erythematosus (SLE). Methods: 16 patients with severe SLE and renal disease, in whom cyclophosphamide was contraindicated or failed to halt disease progression, were treated with IAS for 3 months. Patients achieving at least 20% improvement in two or more of the outcome measures were considered responders and offered a 9 months’ extension period. Results: Within 3 months, 14 patients responded and 11 opted for an extension. Proteinuria decreased from 6.7 (4.6) g/day (mean (SD)) at baseline to 4.3 (3.5) g/day at 3 months and 2.9 (2.4) g/day at 12 months (p<0.001). From baseline to 3 and 12 months, disease activity improved independently of scoring by SIS (15 (5) to 5 (2) and to 5 (2), p<0.0001), SLEDAI (21 (7) to 5 (4) and to 5 (4), p<0.0001), or ECLAM (7 (2) to 2 (1) and to 3 (1), p<0.0001). Anti-dsDNA fell from 391 (647) IU/ml to 146 (218) and to 53 (50) IU/ml at 3 and 12 months, respectively. Steroids could be tapered from 117 (159) mg/day at baseline to 29 (17) mg/day at 3 months and 9 (2) mg/day at 12 months. IAS was not associated with an excess of infections. However, one patient died of septicaemia after 1 month of treatment. Conclusion: In this negatively selected cohort of patients with SLE, IAS was associated with a significant response shown by reduced proteinuria, improved global disease activity, decreased anti-dsDNA, and lower glucocorticoid dosages, suggesting therapeutic benefit.

BackgroundCut offs for low disease activity (LDA) using psoriatic arthritis (PsA) specific composite scores have recently been proposed.1–3 Whether these definitions adequately reflect the absence of inflammation is unknown.ObjectivesTo evaluate these definitions against a low level of activity according to ultrasound examination.MethodsWe performed a prospective study on 83 PsA patients undergoing clinical and ultrasound examinations at two study visits scheduled 6 months apart. LDA was assessed using the Disease Activity index for Psoriatic Arthritis (DAPSA≤14), the Psoriatic ArthritiS Disease Activity Score (PASDAS ≤3.2), the Composite Psoriatic Disease Activity Index (CPDAI≤4), the Disease Activity Score 28 CRP (DAS28-CRP≤2.8) and the Minimal Disease Activity criteria (MDA).Ultrasound (US) evaluation was performed at 68 joints (evaluating synovia, peritendinous tissue, tendons and bony changes) and 14 entheses.Minimal ultrasound disease activity (MUDA) was defined as a Power Doppler (PD) score ≤1, respectively at joints, peritendinous tissue, tendons and entheses.ResultsLDA was present in 33.7%–65.0% of patients at baseline and in 44.3%–80.6% at follow-up examination, depending on the criteria used. MUDA was observed in 16.9% at baseline and in 30% at follow-up.At baseline only the DAPSA-LDA definition was useful to identify MUDA patients (78.6% of patients identified correctly), whereas at follow up >80% of MUDA patients were correctly classified as LDA according to DAPSA, PASDAS, CPDAI and DAS28-CRP.Only DAPSA (Sensitivity (S)=88.2%, Specificity (Sp)=40.5, p=0.033), PASDAS (S=88.2%, Sp=55.0%, p=0.002) and the MDA criteria (S=71.4%, Sp=67.3%, p=0.003) were able to discriminate patients with and without MUDA at follow-up.A global ultrasound inflammation subscore for joints and entheses (GUIS-j/e), containing the above mentioned US variables, was significantly higher in patients with active disease versus patients in LDA according to DAPSA (p=0.002) and PASDAS (p=0.013) at baseline and DAPSA (p=0.007), PASDAS (p=0.001), CPDAI (p=0.021) and the MDA criteria (p<0.001) at follow up.ConclusionsOf all tested LDA definitions, DAPSA was overall the most efficacious in differentiating between high and low ultrasound scores and better identified patients with MUDA as compared to the other tested scores.References[1] Coates LC, Fransen J, Helliwell PS. Defining minimal disease activity in psoriatic arthritis: A proposed objective target for treatment. Annals of the Rheumatic Diseases69(1):48–53.[2] Helliwell PS, FitzGerald O, Fransen J. Composite disease activity and responder indices for psoriatic arthritis: A report from the GRAPPA 2013 meeting on development of cutoffs for both disease activity states and response. The Journal of Rheumatology2014;41(6):1212–7.[3] Schoels MM, Aletaha D, Alasti F, Smolen JS. Disease activity in Psoriatic Arthritis (PsA): Defining remission and treatment success using the DAPSA score. Ann Rheum Dis2016;75(5):811–8.Disclosure of InterestNone declared

Systemic lupus erythematosus (SLE) can be a severe and potentially life-threatening disease that often represents a therapeutic challenge because of its heterogeneous organ manifestations. Only glucocorticoids, chloroquine and hydroxychloroquine, azathioprine, cyclophosphamide and very recently belimumab have been approved for SLE therapy in Germany, Austria and Switzerland. Dependence on glucocorticoids and resistance to the approved therapeutic agents, as well as substantial toxicity, are frequent. Therefore, treatment considerations will include ‘off-label’ use of medication approved for other indications. In this consensus approach, an effort has been undertaken to delineate the limits of the current evidence on therapeutic options for SLE organ disease, and to agree on common practice. This has been based on the best available evidence obtained by a rigorous literature review and the authors’ own experience with available drugs derived under very similar health care conditions. Preparation of this consensus document included an initial meeting to agree upon the core agenda, a systematic literature review with subsequent formulation of a consensus and determination of the evidence level followed by collecting the level of agreement from the panel members. In addition to overarching principles, the panel have focused on the treatment of major SLE organ manifestations (lupus nephritis, arthritis, lung disease, neuropsychiatric and haematological manifestations, antiphospholipid syndrome and serositis). This consensus report is intended to support clinicians involved in the care of patients with difficult courses of SLE not responding to standard therapies by providing up-to-date information on the best available evidence.

Drug-induced hepatotoxicity is a frequent cause of liver disease and acute liver failure, particularly in patients treated with multiple drugs. Several antibacterial drugs have the potential to cause severe liver injury and failure. This article aims to increase the awareness and understanding of drug induced liver injury (DILI) due to antibacterial drugs. It reviews the pattern of antibacterial DILI and provides details on molecular mechanisms and toxicogenomics, as well as clinical data based on epidemiology studies. Certain antibacterial drugs are more frequently linked to hepatotoxicity than others. Therefore, the hepatotoxic potential of tetracyclines,sulfonamides, tuberculostatic agents, macrolides, quinolones,and beta-lactams are discussed in more detail. Efforts to improve the early detection of DILI and the acquisition of high-quality epidemiological data are pivotal for increased patient safety.

We conducted a prospective, randomized study to compare the efficacy of oral fusidic acid, oral metronidazole, oral vancomycin, and oral teicoplanin for the treatment of Clostridium difficile—associated diarrhea. Treatment resulted in clinical cure for 94% of the patients who were treated with vancomycin, 96% of those treated with teicoplanin, 93% of those treated with fusidic acid, and 94% of those treated with metronidazole. Clinical symptoms recurred in 16% of patients treated with vancomycin, 7% of those treated with teicoplanin, 28% of those treated with fusidic acid, and 16% of those treated with metronidazole. There was asymptomatic carriage of C. difficile toxin in 13% of patients treated with vancomycin,4% of those treated with teicoplanin, 24% of those treated with fusidicacid, and 16% of those treated with metronidazole. No adverse effectsrelated to therapy with vancomycin or teicoplanin were observed. Considering the costs of treatment, our findings suggest that metronidazole is the drug of choice for C. difficile—associated diarrhea and that glycopeptides should be reserved for patients who cannot tolerate metronidazole or who do not respond to treatment with this drug.