Pregnancies in women with antineutrophil cytoplasmatic antibody associated vasculitis.

PURPOSE OF REVIEW: Antineutrophil cytoplasmatic antibody associated vasculitis (AAV) usually manifests after age fifty, thus making it very rare during reproductive age. Although rare, AAV, particularly eosinophilic granulomatosis with polyangiitis, can manifest at a younger age. AAV can also appear for the first time during pregnancy. RECENT FINDINGS: Data from pregnant patients with AAV mostly derive from case reports or retrospective studies, with an absolute number of <100 published cases. Therefore, numbers of results of pregnancy outcome vary widely. SUMMARY: As with other chronic autoimmune diseases, patients and infants seem to be at a higher risk for preterm delivery, intrauterine growth retardation and preeclampsia. Possible treatment for AAV in pregnancy depends upon gestational age and include glucocorticosteroids, azathioprine, intravenous immunoglobulins, and in severe cases rituximab and even cyclophosphamide. Plasma exchange might be an option in selected patients. Aside from cyclophosphamide these medications can also be used during breastfeeding. Acetylsalicylic-acid 100-150 mg/day reduces the risk of preeclampsia, also in this population. Patients should be counseled prior to conception and medication that is suitable for pregnancy should be established early on. During pregnancy, we recommend close monitoring of disease activity, blood pressure and ideally to co-consult with a gynecologist in an interdisciplinary approach.

Association of the AAV-PRO questionnaire with established outcome measures in AAV.

OBJECTIVES: The ANCA-associated vasculitis (AAV) patient-reported outcome (AAV-PRO) questionnaire was developed to capture the impact of AAV and its treatment. We investigated the association of specific AAV-PRO domains with disease activity and extent, damage, depression, health-related quality of life, and treatment. METHODS: In a prospective longitudinal study, AAV-PRO, Beck's depression inventory (BDI), Short Form 36 (SF-36), BVAS and Vasculitis Damage Index (VDI) were completed at baseline (t1) and after 3-6 months (t2). In addition, patient data (including diagnosis, therapies, relapses, and organ manifestations) were recorded. Data were analysed by t-tests and correlation-based regression analyses. RESULTS: A total of 156 patients with AAV participated. The mean BVAS at the time of enrolment was 1.4 ± 3.74. The median AAV-PRO domain scores were higher in patients reporting 'active disease' compared with those reporting 'in remission' (P < 0.001). In the correlation analyses, all AAV-PRO domain scores correlated strongly with the BDI (all r ≥ 0.319, all P ≤ 0.001) as well as with all eight SF-36 subdomains (all |r|≥0.267, all P ≤ 0.001). The regression analyses showed that AAV-PRO domains were strongly predicted by the BDI and SF-36 domains (|ß| ≥ 0.240 for the strongest predictor of each domain). In the longitudinal comparison (t1/t2), there were no significant changes in the overall results. CONCLUSION: Our data show convergent validity for all AAV-PRO subdomains, using the established questionnaires BDI and SF-36. The AAV-PRO domains scores were not correlated with clinician-derived instruments (including the BVAS and the VDI). Thus, we regard the AAV-PRO questionnaire as a valuable measure of outcomes that might complement traditional end-points in clinical trials.

Detection of IgE-autoantibodies to nuclear antigens in patients with systemic sclerosis and analysis of their clinical relevance.

OBJECTIVES: Antinuclear antibodies (ANA) of the IgE-type have been described in several connective tissue disorders (CTD) but not yet in systemic sclerosis (SSc). Aim of the study was, therefore, to establish an ELISA for the demonstration of IgE-autoantibodies to topoisomerase-I (topo-I) and the centromeric proteins A and B (CENP-A/B), to assess their prevalence and reactivity in SSc and to analyse their clinical relevance. METHODS: One hundred fifty-one patients with SSc and 88 with CREST-syndrome, 291 patients with other CTD, and 23 patients with fibromyalgia syndrome (FM) as a control collective were included into the study. Patients' sera were analysed by an in-house-ELISA for IgE autoantibodies against topo-I and CENP-A/B using recombinant antigens. Patients were assessed for median Rodnan skin score(mRSS), different organ and cutaneous manifestations. RESULTS: Of the patients with CREST syndrome, 67% had IgE-anti-CENP-A- and 77% IgE-anti-CENP-B-antibodies. IgE-anti-topo-I antibodies were found in 56% of patients with SSc. Prevalence and reactivity were significantly higher in CREST and SSc, respectively, than in other CTD or FM. IgE-reactivity strongly correlated with IgG-antibody reactivity. In CRESTsyndrome, IgE-anti-CENP-A (but not CENP-B)-antibodies were significantly higher and more prevalent in patients with skin ulcers, high mRSS, and more than four organ manifestations. They did not correlate with blood eosinophil counts. In contrast, for IgE-anti-topo-I antibodies no correlation with clinical manifestations was observed. CONCLUSIONS: IgE-autoantibodies against CENP-A/B and topo-I occur in SSc underlining the concept that SSc may be a T helper cell type 2 mediated disease. IgE-anti-CENP-A-antibodies correlated with disease activity, but this has to be confirmed in larger studies.

Mobilization with reduced cyclophosphamide for autologous stem cell transplantation is feasible in patients with systemic sclerosis.

OBJECTIVES: To assess the feasibility of reduced cyclophosphamide dosing in the setting of mobilization chemotherapy prior to high dose chemotherapy and autologous stem cell transplantation in patients with SSc. The primary end point was the occurrence of 'poor mobilization' when using different cyclophosphamide dosing. The second end point was to analyse potential risk factors for difficult stem cell mobilization in this cohort of patients with SSc. METHODS: This single-centre study retrospectively reviewed 32 patients with SSc who underwent autologous stem cell transplantation. We analysed the occurrence of 'poor mobilization' (defined as CD34+ progenitor cell count <2 × 106/kg body weight, the use of increasing G-CSF dose, the use of plerixafor, or leukapheresis on >2 consecutive days) in different cyclophosphamide mobilization regimens: We herein compared low dose (2 × 1-1.5 g/m2) cyclophosphamide vs high dose (2 × 2 g/m2) for mobilization. RESULTS: Higher dosing of cyclophosphamide seems not to be beneficial regarding stem cell collection as there was no significant difference in stem cell yield between high dose and reduced dose cyclophosphamide (6.2 vs 5.2 × 106/kg bodyweight after CD34+ enrichment). Furthermore, higher doses of cyclophosphamide might be associated with more side effects; this difference was, however, not statistically significant. Lower bodyweight and BMI (P < 0.001) as well as rituximab pre-therapy (P < 0.05) and cardiac involvement (P < 0.01) might negatively impact stem cell collection independently from the chosen regimen. CONCLUSION: Our data demonstrate that a reduced cyclophosphamide mobilization regimen seems to be feasible. Risk factors for poor mobilization might be low bodyweight, prior rituximab therapy and cardiac involvement.

Use of platelet inhibitors for digital ulcers related to systemic sclerosis: EUSTAR study on derivation and validation of the DU-VASC model.

OBJECTIVE: To develop and validate the prognostic prediction model DU-VASC to assist the clinicians in decision-making regarding the use of platelet inhibitors (PIs) for the management of digital ulcers in patients with systemic sclerosis. Secondly, to assess the incremental value of PIs as predictor. METHODS: We analysed patient data from the European Scleroderma Trials and Research group registry (one time point assessed). Three sets of derivation/validation cohorts were obtained from the original cohort. Using logistic regression, we developed a model for prediction of digital ulcers (DUs). C-Statistics and calibration plots were calculated to evaluate the prediction performance. Variable importance plots and the decrease in C-statistics were used to address the importance of the predictors. RESULTS: Of 3710 patients in the original cohort, 487 had DUs and 90 were exposed to PIs. For the DU-VASC model, which includes 27 predictors, we observed good calibration and discrimination in all cohorts (C-statistic = 81.1% [95% CI: 78.9%, 83.4%] for the derivation and 82.3% [95% CI: 779.3%, 85.3%] for the independent temporal validation cohort). Exposure to PIs was associated with absence of DUs and was the most important therapeutic predictor. Further important factors associated with absence of DUs were lower modified Rodnan skin score, anti-Scl-70 negativity and normal CRP. Conversely, the exposure to phosphodiesterase-5 inhibitor, prostacyclin analogues or endothelin receptor antagonists seemed to be associated with the occurrence of DUs. Nonetheless, previous DUs remains the most impactful predictor of DUs. CONCLUSION: The DU-VASC model, with good calibration and discrimination ability, revealed that PI treatment was the most important therapy-related predictor associated with reduced DU occurrence.

Late skin fibrosis in systemic sclerosis: a study from the EUSTAR cohort.

OBJECTIVES: The early trajectory of skin fibrosis provides insights into the disease course of systemic sclerosis (SSc) including mortality; however, little is known about late skin fibrosis. The aims of our study were to ascertain the prevalence and characteristics of late skin fibrosis in SSc. METHODS: We developed and tested three conceptual scenarios of late (>5 years after first non-RP feature) skin fibrosis including new worsening of skin disease, and failure to improve after worsening within 5-year window. We defined skin worsening as change in modified Rodnan skin score (mRSS) ≥5 units or ≥25%. Using strict inclusion criteria including complete mRSS, we identified 1,043 (out of 19 115) patients within the EUSTAR database for our analysis. We further restricted analysis within 887 (out of 1043) patients who had lcSSc or dcSSc at baseline. RESULTS: One-fifth of patients among the whole cohort (n = 208/1043, 19.9%) experienced mRSS worsening, including in patients with lcSSc or dcSSc at baseline (n = 193/887, 21.8%). This was largely due to new skin worsening after the 5-year window or failure to improve with worsening within the 5-year window. Patients with lower baseline mRSS and lcSSc were more likely to develop late skin fibrosis. Anti-Scl-70 was associated with progression from baseline lcSSc to dcSSc, and anticentromere was protective. CONCLUSIONS: Late skin fibrosis is not uncommon in SSc. We have identified different patterns relevant to clinical practice and trial design. Late skin fibrosis is a neglected manifestation of SSc and warrants further investigation including to determine clinical outcomes and optimal therapeutic strategy.

Unauthorized change of immunosuppressants by patients with rheumatic diseases in the COVID-19 pandemic: a cross-sectional analysis of a patient survey.

This study provides insight in behavior and perspective of rheumatic patients during the first COVID-19 wave. Especially, we analyzed the patients' fear of COVID-19 and unauthorized change of immunosuppressive medication in consequence of their fear. We hereby provide data from 877 patients with valuable insights into the patients' point of view. We retrospectively interviewed patients of our rheumatic university outpatient clinic. This way, we collected information about the patients' personal point of view. Data like the rheumatic diagnosis and immunosuppressive medication was extracted from the health records. Statistical analysis was conducted using IBM® SPSS® Statistics (version 26). A total of 877 patients were included into our study. We could show that fear of COVID-19 was clearly present in rheumatic patients. Higher fear levels seem to be associated with comorbidity burden. Unauthorized change of immunosuppressive medication was rare in our study (5%). In our study we provide novel insight into patients' point of view and behavior of rheumatic patients. Unauthorized change of immunosuppressive medication was rare (5%) as seen in other studies. The low rate of unauthorized change and high rate of compliance is reassuring since good disease control appears to be prognostically important in the progression of COVID-19 disease. Therefore, as the pandemic continues, treatment decisions should be made in close consultation between patient and practitioner to improve adherence and reduce morbidity and mortality.

Optimal management of ANCA-associated vasculitis before and during pregnancy: current perspectives.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of systemic vasculitis characterized by autoantibodies against neutrophil cytoplasmic antigens (proteinase 3 PR3-ANCA and myeloperoxidase MPO-ANCA) and inflammation of small vessels. AAV include the diagnosis Granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA), which share many clinical and pathological features. Immunomodulatory therapies have significantly improved prognosis during the last decade. Nevertheless, especially in undiagnosed and thus uncontrolled AAV mortality due to renal impairment or pulmonary haemorrhages is still high. AAV are rare in fertile women, as the typical age of manifestation is above 50 years but there are women with AAV who are or want to become pregnant. This review focusses on how to manage patients with AAV planning to become pregnant and during their pregnancy.

CD19-Targeting CAR T Cells for Myositis and Interstitial Lung Disease Associated With Antisynthetase Syndrome.

Importance: Autoimmune disorders can affect various organs and if refractory, can be life threatening. Recently, CD19-targeting-chimeric antigen receptor (CAR) T cells were efficacious as an immune suppressive agent in 6 patients with refractory systemic lupus erythematosus and in 1 patient with antisynthetase syndrome. Objective: To test the safety and efficacy of CD19-targeting CAR T cells in a patient with severe antisynthetase syndrome, a complex autoimmune disorder with evidence for B- and T-cell involvement. Design, Setting, and Participants: This case report describes a patient with antisynthetase syndrome with progressive myositis and interstitial lung disease refractory to available therapies (including rituximab and azathioprine), who was treated with CD19-targeting CAR T cells in June 2022 at University Hospital Tübingen in Tübingen, Germany, with the last follow-up in February 2023. Mycophenolate mofetil was added to the treatment to cotarget CD8+ T cells, hypothesized to contribute to disease activity. Exposure: Prior to treatment with CD19-targeting CAR T cells, the patient received conditioning therapy with fludarabine (25 mg/m2 [5 days before until 3 days before]) and cyclophosphamide (1000 mg/m2 [3 days before]) followed by infusion of CAR T cells (1.23×106/kg [manufactured by transduction of autologous T cells with a CD19 lentiviral vector and amplification in the CliniMACS Prodigy system]) and mycophenolate mofetil (2 g/d) 35 days after CD19-targeting CAR T-cell infusion. Main Outcomes and Measures: The patient's response to therapy was followed by magnetic resonance imaging of the thigh muscle, Physician Global Assessment, functional muscle and pulmonary tests, and peripheral blood quantification of anti-Jo-1 antibody levels, lymphocyte subsets, immunoglobulins, and serological muscle enzymes. Results: Rapid clinical improvement was observed after CD19-targeting CAR T-cell infusion. Eight months after treatment, the patient's scores on the Physician Global Assessment and muscle and pulmonary function tests improved, and there were no detectable signs of myositis on magnetic resonance imaging. Serological muscle enzymes (alanine aminotransferase, aspartate aminotransferase, creatinine kinase, and lactate dehydrogenase), CD8+ T-cell subsets, and inflammatory cytokine secretion in the peripheral blood mononuclear cells (interferon gamma, interleukin 1 [IL-1], IL-6, and IL-13) were all normalized. Further, there was a reduction in anti-Jo-1 antibody levels and a partial recovery of IgA (to 67% of normal value), IgG (to 87%), and IgM (to 58%). Conclusions and Relevance: CD19-targeting CAR T cells directed against B cells and plasmablasts deeply reset B-cell immunity. Together with mycophenolate mofetil, CD19-targeting CAR T cells may break pathologic B-cell, as well as T-cell responses, inducing remission in refractory antisynthetase syndrome.

iNKT cells can effectively inhibit IL-6 production by B cells in systemic sclerosis.

OBJECTIVE: Systemic sclerosis (SSc) is a connective tissue disease with poorly understood pathogenesis and limited treatment options. Patient mortality is rooted predominantly in the development of pulmonary and cardiac complications. The overactivated immune system is assumed to sustain the inflammatory signature of this autoimmune disease. Here, we investigate the potential of immunoregulatory invariant natural killer T (iNKT) cells to inhibit proinflammatory B cell responses in an in vitro model of inflammation. METHODS: B cells from healthy volunteers (n = 17) and patients with SSc (n = 15) were used for functional testing upon lipopolysaccharide (LPS) stimulation in a co-culture system with third-party iNKT cells. Cytokine production was measured with antibody-based immunoassays (ELISA) and intracellular cytokine staining. RESULTS: iNKT cells strongly inhibited the production of proinflammatory interleukin-6 by B cells upon stimulation with LPS in both healthy volunteers and patients with SSc. In a Transwell assay, cell contact between B cells and iNKT cells proved necessary for this inhibitory effect. Similarly, blocking of CD1d on the surface of B cells abolished the immunoregulatory effect of iNKT cells on B cells. B cell subsets with higher expression of CD1d, namely unswitched memory B cells, were more susceptible to iNKT cell inhibition. CONCLUSION: Our in vitro data underline the potential of iNKT cells in the control of SSc and provide a rationale for the use of novel iNKT cell-based therapeutic strategies in the context of autoimmune diseases.

[Biologics for connective tissue diseases and vasculitides]. / Biologika bei Kollagenosen und Vaskulitiden.

Despite therapy with glucocorticoids (GC) and conventional immunosuppressants, patients with connective tissue diseases and vasculitides often develop functionally relevant and prognostically unfavourable internal organ damage. Based on new pathogenetic insights, biologics and small molecules have recently been studied as targeted therapies for collagen vascular diseases and vasculitides. The B lymphocyte stimulator antagonist belimumab has been used for the treatment of systemic lupus erythematosus (SLE) for several years and has recently also been approved as an add-on therapy for lupus nephritis. Anifrolumab, an antibody against the type­1 interferon receptor, has also been shown to be effective in phase III trials for the treatment of SLE. The interleukin (IL)-6-antagonist tocilizumab showed efficacy in the treatment of interstitial lung disease (ILD) in systemic sclerosis (SSc) and thus has been approved in the USA, although the phase III trial had a negative primary endpoint. In Europe the tyrosine inhibitor nintedanib is approved for progressive ILD in SSc. Tocilizumab is approved for the treatment of giant cell arteritis and reduces both the risk of recurrence and the cumulative GC requirement. The B­lymphocyte depleting antibody rituximab is approved for induction and maintenance therapy of granulomatosis with polyangiitis and microscopic polyangiitis (MPA) and is currently also being investigated for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA). In patients with EGPA, the IL­5 antibody mepolizumab leads to improved disease control and reduces GC requirements. A phase III trial of the small molecule antagonist avacopan targeting the complement C5a receptor as a replacement for high-dose GC in induction therapy of GPA and MPA met its primary endpoints. Various other biologics and small molecule antagonists are currently in clinical development for several type of vasculitis and collagen vascular diseases, some of them at advanced stages.

Autologous stem cell transplantation for progressive systemic sclerosis: a prospective non-interventional study from the European Society for Blood and Marrow Transplantation Autoimmune Disease Working Party.

Three randomized controlled trials in early severe systemic sclerosis demonstrated that autologous hematopoietic stem cell transplantation was superior to standard cyclophosphamide therapy. This European Society for Blood and Marrow Transplantation multi-center prospective non-interventional study was designed to further decipher efficacy and safety of this procedure for severe systemic sclerosis patients in real-life practice and to search for prognostic factors. All consecutive adult systemic sclerosis patients undergoing a first autologous hematopoietic stem cell transplantation between December 2012 and February 2016 were prospectively included in the study. Primary endpoint was progression free survival. Secondary endpoints were overall survival, non-relapse mortality, response and incidence of progression. Eighty systemic sclerosis patients were included. Median follow-up duration was 24 (6-57) months after stem cell transplantation using cyclophosphamide plus antithymocyte globulins conditioning for all, with CD34+ selection in 35 patients. At 2 years, progression free survival was 81.8%, overall survival was 90%, response was 88.7% and incidence of progression was 11.9%. The 100 days non-relapse mortality was 6.25% (n=5) with four deaths from cardiac event, including three due to cyclophosphamide toxicity. Modified Rodnan skin score and forced vital capacity improved with time (p< 0.001). By multivariate analysis, baseline skin score >24 and older age at transplant were associated with lower progression free survival (Hazard ration 3.32) and 1.77, respectively). CD34+-selection was associated with better response (Hazard ration: 0.46). This study confirms the efficacy of autologous stem cell transplantation in real-life practice for severe systemic sclerosis using non myeloablative conditioning. Careful cardio-pulmonary assessment to identify organ involvement at patient referral, reduced cyclophosphamide doses and CD34+ selection may improve outcomes. The study was registered at ClinicalTrials.gov: NCT02516124.

Erectile function and connective tissue diseases. Prevalence of erectile dysfunction in German men with systemic sclerosis compared to other connective tissue diseases and healthy subjects.

OBJECTIVES: Women are more frequently affected by connective tissue diseases like systemic sclerosis (SSc). Therefore, few studies exist on male-specific complaints. This study aimed to investigate the prevalence and associated factors of erectile dysfunction (ED) in SSc compared with other connective tissue diseases (CTD) and healthy controls. METHODS: 64 patients were analysed and compared with 123 age-matched HC. The 15-item International Index for Erectile Function (IIEF) questionnaire was used to assess sexual function. The prevalence of depression was quantified by using the validated Beck Depression Inventory (BDI). RESULTS: Mean age was 52.3 years (SD 10.75) for SSc, 52.9 years (SD 11.01) for patients with other CTD and 52.6 (SD 12.37) for HC. Mean IIEF-15 score was 13.6 for SSc, 11.7 for other CTD and 23.6 for HC. ED was significantly more frequent in patients with SSc (55.0%) and other CTD (54.4%) than in HC (12.7%) (p<0.001) and correlated with diseases severity. The mean BDI score was 10.8 for SSc/CTD and 5.4 for HC (p<0.001). With 36.6%, SSc patients suffered more often from a depression than patients with other CTD (17.4%) and HC (6.3%). We found a significant correlation between the IIEF-15 and depression classified by BDI (r= -0.527; p<0.001). CONCLUSIONS: This is the first study to show increased prevalence of ED, especially severe ED, in men with SSc compared to other CTD and age-matched HC. Physicians should be aware of this influence on sexual health and its correlation to depression and disease severity.

Canakinumab for Treatment of Adult-Onset Still's Disease to Achieve Reduction of Arthritic Manifestation (CONSIDER): phase II, randomised, double-blind, placebo-controlled, multicentre, investigator-initiated trial.

BACKGROUND: Inhibition of interleukin (IL)-1 represents a promising treatment option in adult-onset Still's disease (AOSD). OBJECTIVE: To investigate the efficacy and safety of canakinumab in patients with AOSD and active joint involvement by means of a multicentre, double-blind, randomised, placebo-controlled trial. METHODS: Patients with AOSD and active joint involvement (tender and swollen joint counts of ≥4 each) were treated with canakinumab (4 mg/kg, maximum 300 mg subcutaneous every 4 weeks) or placebo. The primary endpoint was the proportion of patients with a clinically relevant reduction in disease activity at week 12 as determined by the change in disease activity score (ΔDAS28>1.2). RESULTS: At enrolment, patients had high active disease with a mean DAS28(ESR) of 5.4 in the canakinumab and 5.3 in the placebo group, respectively. In the intention-to-treat analysis, 12 patients (67%) in the canakinumab group and 7 patients (41%) in the placebo group fulfilled the primary outcome criterion (p=0.18). In the per-protocol analysis, significantly higher American College of Rheumatology (ACR) 30% (61% vs 20%, p=0.033), ACR 50% (50% vs 6.7%, p=0.009) and ACR 70% (28% vs 0%, p=0.049) response rates were observed in the canakinumab group compared with the placebo group. Two patients in the canakinumab group experienced a serious adverse event. CONCLUSION: Although the study was terminated prematurely and the primary endpoint was not achieved, treatment with canakinumab led to an improvement of several outcome measures in AOSD. The overall safety findings were consistent with the known profile of canakinumab. Thus, our data support indication for IL-1 inhibition with canakinumab in AOSD.

Sexual function in German women with systemic sclerosis compared to women with systemic lupus erythematosus and evaluation of a screening test.

OBJECTIVES: To assess and compare sexual dysfunction (SDF) in female patients with systemic sclerosis (SSc) or systemic lupus erythematosus (SLE), to correlate sexual function with disease characteristics and depression, and to evaluate a short questionnaire (Qualisex) as a screening test. METHODS: Female patients with systemic sclerosis or systemic lupus erythematosus in two German tertiary university hospitals were evaluated in a prospective study. A self-designed questionnaire, the Female Sexual Function Index (FSFI), the Qualisex, and the Beck's depression inventory were used. RESULTS: 171 female patients were included into the study (83 with SSc, and 88 with SLE). 62.6% (52 of 83) of SSc patients and 67.0% (59 of 88) of SLE patients were sexually active. Only 9.6% of SSc patients and 14.8% of SLE patients had ever discussed sexual problems with their physician. Significantly more SSc patients would wish to discuss sexuality with their physician more intensively (37.3% vs. 28.4% in SLE patients, p=0.011). Among the 51 sexually active and evaluable SSc patients a mean FSFI of 25.53 (±5.06) was found, with a FSFI value defining sexual dysfunction (SDF) (<26.55) in 49% of patients, which did not differ significantly compared to SLE patients (n=59, mean FSFI 26.92 (±5.17), SDF in 45.8%). The Qualisex correlated significantly with the FSFI, and both Qualisex and FSFI correlated with depressiveness. CONCLUSIONS: Sexual dysfunction (SDF) is a frequent problem in female patients with SSc and SLE. Addressing sexual issues during medical consultation is an unmet need. The Qualisex constitutes a short questionnaire, which is suitable for addressing concerns on sexuality.

Prevalence of autoimmune disease in women with premature ovarian failure.

Objective: The aim of the study was to investigate the relationship between premature ovarian failure and autoimmune disease.Methods: This interdisciplinary prospective study included 52 consecutively recruited women with premature ovarian failure, aged 18-40 years. Diagnosis of premature ovarian failure was defined as amenorrhoea lasting more than 4 months and anti-Müllerian hormone levels below the age-appropriate range. Women with an abnormal karyotype or Fragile X syndrome were excluded from the study. All participants were screened by a rheumatologist for the presence of underlying autoimmune disease.Results: The average age at first diagnosis of premature ovarian failure was 29.5 years; 92.3% of participants (n = 48) presented with a secondary amenorrhoea, while only 7.7% (n = 4) had primary amenorrhoea. Of all 52 participants, 40.4% (n = 21) had at least one confirmed autoimmune disease, including Hashimoto's disease, systemic lupus erythematosus, rheumatoid arthritis, psoriasis, Crohn's disease, polyglandular autoimmune syndrome and coeliac disease. Response rates for hormonal stimulation therapy were low and the presence of autoimmune disease was associated with poor infertility treatment outcome.Conclusions: We found a high prevalence of autoimmune disease in women with premature ovarian failure. Screening for autoimmune diseases should be offered to all women with premature ovarian failure.

[Behçet's Syndrome]. / Behçet-Syndrom.

Behçet's syndrome (BS) is classified as a variable vessel vasculitis. The clinical picture is very diverse and usually requires interdisciplinary collaboration. Pathogenetically, BS seems to take a middle position between a polygenic autoinflammatory disease and an autoimmune disease. New EULAR recommendations were issued in 2018. The therapy depends on which organs are most affected. Since 2016, adalimumab has been approved for the treatment of posterior ocular involvement. Infliximab, interferon a2a, interleukin-1 antagonists and apremilast may be alternative therapies.

Vasodilators and low-dose acetylsalicylic acid are associated with a lower incidence of distinct primary myocardial disease manifestations in systemic sclerosis: results of the DeSScipher inception cohort study.

OBJECTIVES: To investigate the influence of vasodilator drugs on the occurrence of features depending on myocardial ischaemia/fibrosis (ventricular arrhythmias, Q waves, cardiac blocks, pacemaker implantation, left ventricular ejection fraction (LVEF) <55%, and/or congestive heart failure and sudden cardiac death) in systemic sclerosis (SSc). METHODS: 601 patients with SSc were enrolled from 1 December 2012 to 30 November 2015 and had a second visit 0.5-4 years apart. 153 received no vasodilators; 448 received vasodilator therapy (ie, calcium channel blockers and/or ACE inhibitors or angiotensin II receptor blockers or combinations of them), 89 of them being also treated with either endothelin receptor antagonists or PDE5 inhibitors or prostanoids. Associations between the occurrence of myocardial disease manifestations and any demographic, disease and therapeutic aspect were investigated by Cox regression analysis. A Cox frailty survival model with centre of enrolment as random effect was performed. RESULTS: During 914 follow-up patient-years, 12 ventricular arrhythmias, 5 Q waves, 40 cardiac blocks, 6 pacemaker implantations and 19 reduced LVEF and/or congestive heart failure (CHF) occurred. In multivariate Cox regression analysis, vasodilator therapy was associated with a lower incidence of ventricular arrhythmias (p=0.03); low-dose acetylsalicylic acid (ASA) with a lower incidence of cardiac blocks and/or Q waves and/or pacemaker implantation (p=0.02); active disease with a higher incidence of LVEF <55% and/or CHF and cardiac blocks and/or Q waves and/or pacemaker implantation (p=0.05). CONCLUSIONS: The present study might suggest a preventative effect on the occurrence of distinct myocardial manifestations by vasodilator therapy and low-dose ASA.

Comprehensive metabolic and morphologic disease characterization in systemic sclerosis: initial results using combined positron emission tomography and magnetic resonance imaging.

BACKGROUND: The aim of this study was to evaluate the role of metabolic and morphologic parameters derived from simultaneous hybrid PET/MRI in correlation to clinical criteria for an image-based characterization of musculoskeletal, esophagus and lymph node involvement in systemic sclerosis (SSc). METHODS: Between November 2013 and May 2015, simultaneous whole-body hybrid PET/MRI was performed in 13 prospectively recruited patients with SSc. A mean dose of 241.3 MBq 2-deoxy-2-[18F]fluoro-D-glucose (FDG) was injected. SUVmean and SUVmax values were measured in the spinal bone marrow, spleen, joints, muscles, fasciae, mediastinal lymph nodes and esophagus. MRI abnormalities were scored as 0 (absent), 1 (moderate) and 2 (marked). In addition, organ and skin involvement were graded with clinical sum score (CSS) and modified Rodnan skin score (mRSS), respectively. RESULTS: Results indicate positive correlations between mRSS and fascial FDG-uptake values (fascia summed SUVmax ρ=0.67; fascia summed SUVmean ρ=0.66) that performed better than the MRI sum score (ρ=0.50). Fascial FDG-uptake is also useful in the differentiation between diffuse and limited SSc. Additionally, FDG-PET detected patients with active mediastinal lymphadenopathy and MRI proved to be useful for the delineation of esophagus involvement. CONCLUSIONS: Fascial FDG-uptake has a strong correlation with mRSS and can discriminate between limited and diffuse SSc. These results and the detection of active lymphadenopathy and esophagus involvement can identify patients with advanced scleroderma. Combined PET/MRI therefore provides complementary information on the complex pathophysiology and may integrate several imaging procedures in one.

Trends in employment and hospitalisation in patients with Sjögren's syndrome 1996-2016: results from the German National database.

OBJECTIVES: To assess trends in treatments and outcomes in patients with primary Sjögren's syndrome (pSS), focusing on employment, hospitalisation and medical treatment in the past two decades. METHODS: From 1996 to 2016, approximately 300 patients with pSS were annually documented in the National Database of the German Collaborative Arthritis Centres. Data on treatment, physicians' assessments of disease activity, patient-reported outcomes, hospitalisation and employment were collected and compared to patients with rheumatoid arthritis (RA), matched 1:1 for age, sex and disease duration for each calendar year. RESULTS: Patients with pSS (>90% female, age 44 years at disease onset, disease duration 10 years) were more frequently assessed to be in low disease activity in 2016 (93%) than in 1996 (62%), p<0.01. Treatment with antimalarials increased from 1996 to 2016 (31 to 50%, p<0.01) and less patients were on glucocorticosteroids (50 to 34%, p<0.01) but <5% were treated with biologics. Employment (<65 years) increased by 21 percentage points (43 to 64%, p<0.001), exceeding the increase observed for RA patients (+15 percentage points). Early retirement (22 to 10%, p=0.01), hospitalisation/year (13 to 7%, p=0.08) and sick leave (39% in 1997 to 27%, p=0.09) decreased comparably to RA patients. CONCLUSIONS: Overall, similar trends were observed for RA and pSS cohorts despite minor changes in pSS therapy. Work participation has improved significantly over two decades in pSS. A greater perception of pSS without systemic manifestations may have caused a shift towards less severely affected patient cohorts today.