Analysis of treatment outcomes in patients with antineutrophil cytoplasmic antibody-associated vasculitis on rituximab therapy.

Objectives: This study aimed to analyze a group of patients with severe and refractory antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) managed with rituximab and to report on treatment outcomes. Patients and methods: A total of 78 patients (41 females, 37 males; mean age: 50.1±13.4 years; range, 18 to 76 years) with AAV on rituximab treatment were included in the single-center, retrospective study conducted between 2009 and 2018. The diagnosis was established based on the 1990 classification criteria of the American College of Rheumatology and the definitions of vasculitis of Chapel Hill Consensus Conference. Laboratory and immunological tests were conducted. Disease activity was determined through the Birmingham Vasculitis Activity Score. Results: Rituximab was preferred over cyclophosphamide in 37 patients and used as a second-line therapy after cyclophosphamide in 41 cases. Rituximab treatment showed favorable outcomes with regard to serum creatinine levels, proteinuria, and hematuria, as well as in cases of isolated lung involvement. Nearly half of patients with pulmonary renal syndrome also improved, with 22.2% achieving remission. ANCAs were positive in 85.9% of patients at the onset of rituximab treatment and became negative in 82% of the positive cases. Adverse events were rare and included infusion reactions (one case of reactivation of a herpes zoster infection and one case of allergic reaction). Conclusion: Rituximab is an efficient and safe therapeutic option in patients with AAV who are difficult to treat, have insufficient response, or have not tolerated other treatments.

Interim 2-Year Analysis from SERENA: A Real-World Study in Patients with Psoriatic Arthritis or Ankylosing Spondylitis Treated with Secukinumab.

INTRODUCTION: Sustained improvement of high degree in clinical outcomes have been demonstrated in phase 3 trials with secukinumab in both psoriatic arthritis (PsA) and ankylosing spondylitis (AS). The objective of the SERENA study was to evaluate the effectiveness, retention rates, and safety of secukinumab in patients with PsA and AS. METHODS: SERENA is an ongoing, longitudinal, real-world observational study involving patients with moderate-to-severe psoriasis, PsA, or AS. Patients had received at least 16 weeks of secukinumab treatment before recruitment to the study. Retention rate was defined as percentage of patients who continued secukinumab treatment over the course of study. Effectiveness of secukinumab in AS and PsA cohorts was assessed using descriptive statistics. RESULTS: The current interim analysis included 1004 patients with PsA or AS. Overall secukinumab retention rates at 2 years after enrolment were 74.9 and 78.9% in patients with PsA and AS, respectively. At baseline and at 2 years, swollen joint count [3.3 (5.8) vs. 2.9 (5.8)], tender joint count [6.3 (9.4) vs. 5.6 (7.2)] in patients with PsA and BASDAI scores [3.2 (2.3) vs. 2.9 (2.3)] in patients with AS, suggest sustained effectiveness for patients remaining on secukinumab for at least 2 years after enrolment. A total of 73 patients had treatment interruption; 78% of these patients reinitiated secukinumab without a loading dose. No new or unexpected safety signals were reported. CONCLUSIONS: After more than 2 years since initiation, secukinumab demonstrated high retention rates and favorable safety profile as well as sustained effectiveness in patients who continued secukinumab treatment.

Alterations of serum levels of plasminogen, TNF-α, and IDO in granulomatosis with polyangiitis patients.

BACKGROUND: Granulomatosis with polyangiitis (GPA) is a representative of vasculitides associated with anti-neutrophil cytoplasmic autoantibodies. "Classical" antibodies directed against proteinase 3 are involved in the pathogenesis and are part of the GPA diagnosis at the same time. Along with them, however, antibodies against Lysosomal-Associated Membrane Protein-2 (LAMP-2) and antibodies directed against plasminogen have been described in GPA.Objectives and methodology: We performed a cross-sectional study enrolling 34 patients diagnosed with GPA. Our study was aimed at looking for correlations between serum levels of LAMP-2 and plasminogen and the clinical manifestations of the GPA. Furthermore, we examined serum levels of tumor necrosis factor-alpha (TNF-α) and its associated indoleamine-pyrrole 2,3-dioxygenase (IDO), as well as we looked for a correlation between these cytokines and the clinical manifestations of GPA. RESULTS: The results showed that in GPA, serum plasminogen levels were negatively associated with renal involvement (receiver operating characteristic (ROC) area under the curve (AUC) of 0.78) (95% CI 0.53-0.91), p = 0.035, and the extent of proteinuria, Spearman's Rho = -0.4, p = 0.015. Increased levels of TNF-α and IDO correlated with disease activity, Spearman's Rho =0.62, p = 0.001 and Spearman's Rho = 0.4, p = 0.022, respectively, whereas only TNF-α was increased in severe forms of GPA with lung involvement (ROC AUC of 0.8) (95% CI 0.66-0.94), p = 0.005. CONCLUSIONS: In this study, we demonstrate the alteration of soluble factors, which play an important role in the pathogenesis of GPA and their relationship with the clinical manifestations of the disease. Our main results confirm the associations of increased secretory TNF-α and some clinical manifestations, and we describe for the first time decreased serum plasminogen levels and their association with renal involvement.

Rheumatological aspects of pathogenesis and treatment of COVID-19 infection.

Contemporary rheumatology is a field dealing with the phenomena of autoimmune states and inflammation. Rheumatic diseases cover a wide spectrum of diseases of the musculoskeletal system, connective tissue and vessels. The occurrence of an immune, autoimmune and autoinflammatory response is often linked to different kinds of infections. Which aspects of the coronavirus infection relate to rheumatological therapy and practice? In order to answer this question one needs to look at the pathogenesis of the SARS-CoV-2 infection. Antimalarial drugs may block antigen presentation of the viral peptides from antigen presenting cells, as they may alter the lysosomal proteases that mediate the viral entry in the cells and have demonstrated efficacy in improving the infection. Anti-IL-6 may interfere with cytokine storm in severe cases and use of tocilizumab has had good results in a small cohort. Baricitinib not only plays a role in inhibiting the synthesis of cytokines but it also has a function in suppressing receptor-mediated endocytosis. The constantly new and tested concepts in the treatment of COVID testify to the growing knowledge about the virus, but also to the need for more targeted therapy. Treatment regimens have been developed for both patients with COVID-19 and those with symptomatic SARS-CoV infection and rheumatic disease. This article is an attempt to discuss the management of COVID-19 and coexisting rheumatic disease.

Secukinumab Use in Patients with Moderate to Severe Psoriasis, Psoriatic Arthritis and Ankylosing Spondylitis in Real-World Setting in Europe: Baseline Data from SERENA Study.

INTRODUCTION: Secukinumab, a fully human monoclonal antibody that directly inhibits interleukin-17A, has demonstrated robust efficacy in the treatment of moderate to severe psoriasis (PsO), psoriatic arthritis (PsA) and ankylosing spondylitis (AS), with a rapid onset of action, sustained long-term clinical responses and a consistently favourable safety profile across phase 3 trials. Here, we report the clinical data at enrolment from SERENA, designed to investigate the real-world use of secukinumab across all three indications. METHODS: SERENA is an ongoing, longitudinal, observational study conducted at 438 sites across Europe in patients with moderate to severe plaque PsO, active PsA or active AS. Patients should have received at least 16 weeks of secukinumab treatment before enrolment in the study. RESULTS: Overall 2800 patients were included in the safety set; patients with PsA (N = 541) were older than patients with PsO (N = 1799) and patients with AS (N = 460); patients with PsO had a higher mean body weight than patients with PsA and patients with AS; and patients with PsO and patients with AS were predominantly male. Time since diagnosis was longer in patients with PsO compared with patients with PsA and patients with AS, and about 40% of patients were either current or former smokers. The proportion of obese patients (body mass index ≥ 30 kg/m2) was similar across indications. Patients were treated with secukinumab for a mean duration of 1 year prior to enrolment (range 0.89-1.04). The percentages of patients with prior biologics exposure were 31.5% PsO, 59.7% PsA and 55% AS. The percentages of patients prescribed secukinumab monotherapy were 75% (n = 1349) in PsO, 48.2% (n = 261) in PsA and 48.9% (n = 225) in AS groups. CONCLUSION: Baseline demographics of the study population are consistent with existing literature. This large observational study across all secukinumab indications will provide valuable information on the long-term effectiveness and safety of secukinumab in the real-world setting.

Severe mononeuritis multiplex in a patient with eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic vasculitis characterised by bronchial asthma, hypereosinophilia, and systemic vasculitis. History of asthma with blood eosinophilia and multiorgan involvement are the important clues to suspect EGPA. In the original paper by Churg and Strauss cardiac, gastrointestinal tract, renal, and neurological involvement were noted more frequently. The pattern of neurological involvement may be mononeuritis multiplex, and symmetrical and asymmetrical polyneuropathy. Mononeuritis multiplex was present in 78.1% while cranial nerves were involved in only 4.1% of cases. Glucocorticosteroids and immunosuppressants, especially cyclophosphamide, have considerably improved the prognosis and overall survival rates in patients with systemic vasculitis, including eosinophilic granulomatosis with polyangiitis. The authors present a clinical case of eosinophilic granulomatosis with polyangiitis with severe mononeuritis multiplex. The case reflects the successful application of a cyclophosphamide regime as a remission inducer.

Coincidence of Guillain-Barré syndrome presenting with Landry's acute flaccid paralysis and transverse myelitis.

Transverse myelitis is one of the causes of acute transverse myelopathy; three main categories are described in the differential diagnosis of transverse myelitis: demyelination (multiple sclerosis, neuromyelitis optica), infections (herpes zoster and herpes simplex virus), and some autoimmune connective tissue disorders (systemic lupus erythematosus, vasculitis). The authors present a clinical case of a 33-year-old patient with transverse myelitis occurring in the course of acute inflammatory demyelinating polyradiculoneuropathy (Guillain-Barré syndrome). The patient's medical history was notable. The patient was diagnosed with thrombotic thrombocytopenic purpura (Moschcowitz syndrome) and leukocytoclastic vasculitis when he was 12 years old.

Spondylodiscitis developing in a young man - diagnostic and therapeutic difficulties.

Infectious spondylodiscitis is characterized by vertebral osteomyelitis, spondylitis, and discitis. Patients present with persistent low back pain, fever, or neurological findings. Diagnosis is made with a combination of clinical, radiological, and laboratory findings. Magnetic resonance tomography (MRI) has high sensitivity and specificity in diagnosis and differentiation of the type of spondylodiscitis and may reveal signs of spondylodiscitis even in very early stages. Infectious spondylodiscitis responds to antimicrobial therapy well if diagnosed early before development of neurological deficit and requirement of surgical intervention. We present a clinical case of spondylodiscitis developing in a young immunocompetent man without any predisposing factors.

Cartilage oligomeric protein, matrix metalloproteinase-3, and Coll2-1 as serum biomarkers in knee osteoarthritis: a cross-sectional study.

Biochemical markers reflecting joint remodeling in osteoarthritis (OA) are a promising diagnostic tool. The aim of this study was to investigate serum levels of candidate biomarkers in subjects with and without knee OA and assess their correlation with clinical parameters and knee structural damage. 56 patients with primary knee OA and 31 healthy controls participated in this study. Patients were separated into two groups: isolated knee OA and generalized OA. Clinical parameters were obtained by validated self-reported questionnaires and a visual analogue scale. Serum levels of cartilage oligomeric protein (COMP), matrix metalloproteinase-3 (MMP-3), and Coll2-1 were quantified by enzyme-linked immunosorbent assay. Knee structural damage was determined by plain X-ray and 1.5 T magnetic resonance imaging (MRI), using Kellgren-Lawrence (KL) grading scale and Whole-Organ Magnetic Resonance Imaging Score (WORMS), respectively. Compared to controls, patients had significantly higher median serum COMP (985 vs. 625 ng/ml; p < 0.001) and MMP-3 (36.85 vs. 22.10 ng/ml; p = 0.003) levels. Patients with radiographic evidence of KLII/III knee OA had greater median COMP levels than KLI patients (1095 vs. 720 ng/ml; p = 0.001). In the generalized OA group, mean MMP-3 levels were higher than in the isolated knee OA group (30.40 vs. 55.13 ng/ml; p < 0.001). COMP correlated positively with WORMS (r s = 0.454, p < 0.001) and MMP-3 (r s = 0.337, p = 0.003). Cut-off values for serum COMP and MMP-3 were determined. We observed higher serum COMP and MMP-3 levels in knee OA patients compared to controls. COMP may reflect knee structural damage, while MMP-3-OA "generalization".

Treg/Th17 cell balance and phytohaemagglutinin activation of T lymphocytes in peripheral blood of systemic sclerosis patients.

AIM: To investigate T-cell activation, the percentage of peripheral T regulatory cells (Tregs), Th17 cells and the circulating cytokine profile in systemic sclerosis (SSc). METHODS: We enrolled a total of 24 SSc patients and 16 healthy controls in the study and divided the patients as having diffuse cutaneous SSc (dcSSc, n = 13) or limited cutaneous SSc (lcSSc, n = 11). We performed a further subdivision of the patients regarding the stage of the disease - early, intermediate or late. Peripheral venous blood samples were collected from all subjects. We performed flow cytometric analysis of the activation capacity of T-lymphocytes upon stimulation with PHA-M and of the percentage of peripheral Tregs and Th17 cells in both patients and healthy controls. We used ELISA to quantitate serum levels of human interleukin (IL)-6, IL-10, tissue growth factor-ß1 (TGF-ß1), and IL-17A. RESULTS: We identified a decreased percentage of CD3+CD69+ cells in PHA-stimulated samples from SSc patients in comparison with healthy controls (13.35% ± 2.90% vs 37.03% ± 2.33%, P < 0.001). However, we did not establish a correlation between the down-regulated CD3+CD69+ cells and the clinical subset, nor regarding the stage of the disease. The activated CD4+CD25+ peripheral lymphocytes were represented in decreased percentage in patients when compared to controls (6.30% ± 0.68% vs 9.36% ± 1.08%, P = 0.016). Regarding the forms of the disease, dcSSc patients demonstrated lower frequency of CD4+CD25+ T cells against healthy subjects (5.95% ± 0.89% vs 9.36% ± 1.08%, P = 0.025). With regard to Th17 cells, our patients demonstrated increased percentage in comparison with controls (18.13% ± 1.55% vs 13.73% ± 1.21%, P = 0.031). We detected up-regulated Th17 cells within the lcSSc subset against controls (20.46% ± 2.41% vs 13.73% ± 1.21%, P = 0.025), nevertheless no difference was found between dcSSc and lcSSc patients. Flow cytometric analysis revealed an increased percentage of CD4+CD25-Foxp3+ in dcSSc patients compared to controls (10.94% ± 1.65% vs 6.88% ± 0.91, P = 0.032). Regarding the peripheral cytokine profile, we detected raised levels of IL-6 [2.10 (1.05-4.60) pg/mL vs 0.00 pg/mL, P < 0.001], TGF-ß1 (19.94 ± 3.35 ng/mL vs 10.03 ± 2.25 ng/mL, P = 0.02), IL-10 (2.83 ± 0.44 pg/mL vs 0.68 ± 0.51 pg/mL, P = 0.008), and IL-17A [6.30 (2.50-15.60) pg/mL vs 0 (0.00-0.05) pg/mL, P < 0.001] in patients when compared to healthy controls. Furthermore, we found increased circulating IL-10, TGF-ß, IL-6 and IL-17A in the lcSSc subset vs control subjects, as it follows: IL-10 (3.32 ± 0.59 pg/mL vs 0.68 ± 0.51 pg/mL, P = 0.003), TGF-ß1 (22.82 ± 4.99 ng/mL vs 10.03 ± 2.25 ng/mL, P = 0.031), IL-6 [2.08 (1.51-4.69) pg/mL vs 0.00 pg/mL, P < 0.001], and IL-17A [14.50 (8.55-41.65) pg/mL vs 0.00 (0.00-0.05) pg/mL, P < 0.001]. Furthermore, circulating IL-17A was higher in lcSSc as opposed to dcSSc subset (31.99 ± 13.29 pg/mL vs 7.14 ± 3.01 pg/mL, P = 0.008). Within the dcSSc subset, raised levels of IL-17A and IL-6 were detected vs healthy controls: IL-17A [2.60 (0.45-9.80) pg/mL vs 0.00 (0.00-0.05) pg/mL, P < 0.001], IL-6 [2.80 (1.03-7.23) pg/mL vs 0.00 pg/mL, P < 0.001]. Regarding the stages of the disease, TGF-ß1 serum levels were increased in early stage against late stage, independently from the SSc phenotype (30.03 ± 4.59 ng/mL vs 13.08 ± 4.50 ng/mL, P = 0.017). CONCLUSION: It is likely that the altered percentage of Th17 and CD4+CD25-FoxP3+ cells along with the peripheral cytokine profile in patients with SSc may play a key role in the pathogenesis of the disease.

The challenge of the definition of early symptomatic knee osteoarthritis: a proposal of criteria and red flags from an international initiative promoted by the Italian Society for Rheumatology.

The aim of this study was to establish consensus for potential early symptomatic knee osteoarthritis (ESKOA) clinical definition and referral criteria from primary care to rheumatologists, based on available data from literature and a qualitative approach, in order to perform studies on patients fulfilling such criteria and to validate the obtained ESKOA definition. A complex methodological approach was followed including: (1) three focus groups (FG), including expert clinicians, researchers and patients; (2) a systematic literature review (SLR); (3) two discussion groups followed by a Delphi survey. FG and SLR were performed in parallel to inform discussion groups in order to identify relevant constructs to be included in the modified Delphi survey. ESKOA is defined in the presence of: (a) two mandatory symptoms (knee pain in the absence of any recent trauma or injury and very short joint stiffness, lasting for less than 10 min, when starting movement) even in the absence of risk factors, or (b) knee pain, and 1 or 2 risk factors or (c) three or more risk factors in the presence of at least one mandatory symptom, with symptoms lasting less than 6 months. These criteria are applicable in the absence of active inflammatory arthritis, generalized pain, Kellgren-Lawrence grade >0, any recent knee trauma or injury, and age lower than 40 years. Knee pain in the absence of any recent trauma lasting for less than 6 months was considered as the referral criterion to the rheumatologist for the suspicion of ESKOA. This consensus process has identified provisional clinical definition of ESKOA and defined potential referral criterion to rheumatologist, in order to test ESKOA obtained definition in prospective validation studies.

Organising pneumonia - the first manifestation of rheumatoid arthritis.

Organising pneumonia (OP) is a distinct type of interstitial lung disease, because it can also be seen in association with several conditions such as infections, drugs, and connective tissue diseases. An association of OP with rheumatoid arthritis (RA) has also been described. Joint manifestations of RA usually precede lung involvements by several years; however, in less than 10% of cases of RA, interstitial lung disease may be the initial feature of RA. Organising pneumonia as the initial manifestation or developed simultaneously of RA is extremely rare, and its clinical features remain unknown. We present a 56-year-old woman with OP as the first manifestation of RA.

Two clinical cases of granulomatosis with polyangiitis with isolated otitis media and mastoiditis.

Granulomatosis with polyangiitis (GPA) is characterised by granulomatous necrotising inflammatory lesions of the upper and lower respiratory tract, often associated with pauci-immune glomerulonephritis. The diagnosis of granulomatosis with polyangiitis is made according to the classification criteria of the ACR criteria for granulomatosis with polyangiitis. We present two cases of granulomatosis with polyangiitis limited/localised form. The common feature between two clinical cases were not sufficient criteria for a definite diagnosis at the beginning. In both cases the clinical presence was otitis media with acute mastoiditis, peripheral facial nerve palsy, and severe headache. Early diagnosis and treatment of patients with granulomatosis with polyangiitis define favourable prognosis. On the other hand, the treatment of granulomatosis with polyangiitis (corticosteroids and immunosuppressive therapy) has various side effects, and the "ex juvantibus" therapy is hazardous.

Impact of lumbar syndesmophyte on bone health as assessed by bone density (BMD) and bone texture (TBS) in men with axial spondyloarthritis.

INTRODUCTION: Patients with spondyloarthritis (SpA) have an elevated incidence of osteoporosis and are at increased risk of pathological vertebral fracture. Evaluation of bone density by dual energy X-ray absorptiometry (DXA) has its limits in fracture prediction, already known in this population. One hypothesis is that the presence of lumbar syndesmophyte could overestimate the spine bone mineral density (BMD). Trabecular bone score (TBS) is a new texture measurement correlated with bone microarchitecture. Previous studies have shown that TBS is mildly impacted by osteoarthritis and thus could be a predictor of fracture better than spine BMD. We aimed to evaluate a male population of SpA with BMD and TBS measurement and see the impact of lumbar syndesmophytes. METHOD: Two cohorts of SpA male patients (Lausanne, Sofia) with SpA disease, clinical and bone parameters (femoral neck and total spine BMD+spine TBS) were merged. We compared BMD and TBS results regarding to the presence/absence of syndesmophytes. RESULTS: Our study concerned 51 men [29 with lumbar syndesmophytes (L1 to L4,≥1), 22 without], fulfilling the European Spondyloarthropathy Study Group (ESSG) and the Assessment of SpondyloArthritis international Society (ASAS) criteria. Mean age was 52.18 years old (no difference between the 2 groups) and mean body mass index (BMI) 27.47kg/m2 (29.12±0.67 with and 25.30±0.81 without, P=0.0006). For the overall population mean BMD T-score at the spine was -0.55±1.54, mean BMD T-score at the femoral neck -1.20±0.95 and mean lumbar spine TBS was 1.26±0.13. Regarding to the presence or the absence of syndesmophytes, mean spine BMD T-score was -0.07±1.63 and -1.18±1.16 (P=0.009 and 0.250 before and after adjustment for BMI), mean femoral neck BMD T-score was -1.37±0.93 and -0.97±0.94 (P=0.14 and 0.03 before and after adjustment for BMI) and mean TBS was 1.21±0.12 and 1.33±0.11 (P=0.001 and 0.06 before and after adjustment for BMI) respectively for SpA men with and without syndesmophytes. CONCLUSION: Our results showed that SpA men with and without syndesmophytes have lower results compared to the normal population regarding hip BMD, spine TBS and spine BMD except for men with syndesmophytes who have a normal BMD spine T-score. These results suggest that TBS is not influenced by the syndesmophytes in opposite to spine BMD and could be measured in this population in addition to the neck BMD to assess the bone fragility.

Ultrasonographic measurement of carotid artery resistive index and diastolic function of the heart in gout patients.

The aim of the study was to establish the functional disorder in the blood circulation of gout patients with a method that shows early damage of the heart and vascular structures. A total of 117 patients were examined cross-sectionally by a complex multimodal ultrasonography and were divided into four groups: 37 healthy controls, 24 asymptomatic hyperuricemia, 36 gout without tophi and 20 gouty tophi. With pulsed Doppler, common carotid artery resistive index (CCARI) and parameters of the transmitral blood flow were determined: the ratio between maximal early and late flow velocities (E/A ratio) and deceleration time (DT). With tissue Doppler imaging, mitral annular peak velocity (Em) was obtained. In the examined ultrasonographic parameters between healthy controls and the three patient groups, there was a statistically significant difference (p < 0.001). Comparing asymptomatic hyperuricemia and gout without tophi, no significant difference in CCARI (p = 0.656), E/A ratio (p = 0.472), DT (p = 0.990) and Em (p = 0.488) was found. Gouty tophi in comparison with gout without tophi and asymptomatic hyperuricemia had significantly lower Em (mean ± SD 0.07 ± 0.02 vs 0.09 ± 0.03 vs 0.13 ± 0.17) and significantly higher CCARI (mean ± SD 0.74 ± 0.05 vs 0.70 ± 0.05 vs 0.69 ± 0.05). Further multiple logistic regression revealed that tophi increased subject's likelihood of having category of CCARI ≥ 0.7 with an OR = 10.91 (95 % CI 1.80-66.14, p = 0.009), while the category of Em < 0.08 m/s was influenced by renal insufficiency with an OR = 3.07 (95 % CI 1.17-8.02, p = 0.022). Gouty tophi are associated with progression of arteriosclerotic-type vessel changes. Worsening of diastolic dysfunction of the heart is independently associated with renal insufficiency. In terms of CV risk, tophi are an indicator of its increase.

Women's health and fertility, family planning and pregnancy in immune-mediated rheumatic diseases: a report from a south-eastern European Expert Meeting.

With current advances in medical treatment, reproductive issues have become more important for women with chronic immune-mediated diseases. Most, if not all, patients report that their disease affects their personal relationships, their decision to have children, and the size of their family. These decisions are multi-factorial, influenced mainly by concerns over the effect of pregnancy on the rheumatic disease, the impact of disease activity during pregnancy on foetal health, the patient's ability to care for the child, and the possible harmful effects medication could have on the child, both pre- and post-natally during breastfeeding. Apart from that, women's health issues tend to be overlooked in favour of the management of the underlying rheumatic disease. To this end, we convened an expert panel to review the published literature on women's health and reproductive issues and provide evidence- and eminence-based points to consider for the treating physicians. We conclude that there is a need for a change in mind-set from one which 'cautions against pregnancy' to one which 'embraces pregnancy' through the practice of individualised, pre- and post-conceptual, multi-disciplinary care.

Evaluating spine micro-architectural texture (via TBS) discriminates major osteoporotic fractures from controls both as well as and independent of site matched BMD: the Eastern European TBS study.

The aim of the study was to assess the clinical performance of the model combining areal bone mineral density (aBMD) at spine and microarchitecural texture (TBS) for the detection of the osteoporotic fracture. The Eastern European Study is a multicenter study (Serbia, Bulgaria, Romania and Ukraine) evaluating the role of TBS in routine clinical practice as a complement to aBMD. All scans were acquired on Hologic Discovery and GE Prodigy densitometers in a routine clinical manner. The additional clinical values of aBMD and TBS were analyzed using a two steps classification tree approach (aBMD followed by TBS tertiles) for all type of osteoporotic fracture (All-OP Fx). Sensitivity, specificity and accuracy of fracture detection as well as the Net Reclassification Index (NRI) were calculated. This study involves 1031 women subjects aged 45 and older recruited in east European countries. Clinical centers were cross-calibrated in terms of BMD and TBS. As expected, areal BMD (aBMD) at spine and TBS were only moderately correlated (r (2) = 0.19). Prevalence rate for All-OP Fx was 26 %. Subjects with fracture have significant lower TBS and aBMD than subjects without fracture (p < 0.01). TBS remains associated with the fracture even after adjustment for age and aBMD with an OR of 1.27 [1.07-1.51]. When using aBMD T-score of -2.5 and the lowest TBS tertile thresholds, both BMD and TBS were similar in terms of sensitivity (35 vs. 39 %), specificity (78 vs. 80 %) and accuracy (64 vs. 66 %). aBMD and TBS combination, induced a significant improvement in sensitivity (+28 %) and accuracy (+17 %) compared to aBMD alone whereas a moderate improvement was observed in terms of specificity (+9 %). The overall combination gain was 36 % as expressed using the NRI. aBMD and TBS combination decrease significantly the number of subjects needed to diagnose from 7 for aBMD alone to 2. In a multi-centre Eastern European cohort, we have shown that the use of TBS in addition to the aBMD permit to reclassified correctly more than one-third of the overall subjects. Furthermore, the number of subjects needed to diagnose fell to 2 subjects. Economical studies have to be performed to evaluate the gain induced by the use of TBS for the healthcare system.

Association of single nucleotide polymorphism at position -308 of the tumor necrosis factor-alpha gene with ankylosing spondylitis and rheumatoid arthritis.

In this study, we analyzed the putative association between the -308 G/A polymorphism in the promoter region of the tumor necrosis factor (TNF) α gene (rs1800629) and chronic inflammatory arthritis in the Bulgarian population. A case-control study was carried out on 58 patients with ankylosing spondylitis (AS), 108 rheumatoid arthritis (RA) patients and 177 healthy subjects. -308 G/A TNF-α genotypes of patients and controls were determined by restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR). No significant association between the rs1800629 polymorphism and RA risk in the study cohort was observed. However, there were significant differences in the genotype and allele frequencies of the -308 G/A TNF-α polymorphism between AS patients and the healthy subjects. In logistic regression analysis, the presence of the TNF-α -308A allele in the genotype (AA + AG vs. GG) was associated with a 3.298 times lower risk of developing AS. In addition, in AS, there were associations for age at disease onset (<29 years; odds ratio (OR) = 0.222), disease severity (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score > 4; OR = 0.152) and response to anti-TNF treatment (OR = 2.25) under a dominant model (AA + AG vs. GG). In conclusion, our results suggested that the promoter polymorphism -308 G/A in the TNF-α gene had no significant effect on RA development, but could play a role in AS development and in determining the age of disease onset, disease severity and therapeutic outcome of AS in the Bulgarian patients who participated in our study.

Denosumab improves bone mineral density and microarchitecture and reduces bone pain in women with osteoporosis with and without glucocorticoid treatment.

Osteoporosis is a key health problem in postmenopausal women with high social and economic impact. Decreased bone mineral density (BMD) and deterioration of bone microarchitecture may occur also as a result of long-term glucocorticoid treatment (GCT) of autoimmune or inflammatory conditions. Denosumab specifically inhibits the binding of the receptor activator of nuclear factor-κB to its ligand, thus preventing osteoclast activation and bone resorption. The efficacy and safety of denosumab, administered subcutaneously as 60 mg, once every six months for 12 months, were evaluated in 60 patients with postmenopausal osteoporosis (PMO) divided into two groups. The GCT group included 30 patients receiving concomitant glucocorticoid therapy and the non-GCT group included 30 patients that did not receive GCT. In the non-GCT group, the 12-month treatment with denosumab resulted in BMD increase of 6.1% and 2.8% in lumbar spine and hip, respectively. T-score increased by 13.1% and 5.6% in both, the lumbar spine and hip. A slight rise in the Trabecular Bone Score (TBS) of 0.3% was observed. Bone pain was markedly reduced by 56.2%. In the GCT group, denosumab therapy increased BMD with 5.8% and 2.3% in lumbar spine and hip, respectively. T-score of lumbar spine and hip significantly increased by 14.0% and 4.4%, and the TBS rose by 5%. Bone pain was reduced by 53.6%. These data confirm the available knowledge on denosumab efficacy and safety in women with PMO and also provide new insights into its therapeutic potential in patients with osteoporosis related to a long-term corticosteroid treatment.