Phase 2 Trial of Iberdomide in Systemic Lupus Erythematosus.

BACKGROUND: Iberdomide, a cereblon modulator promoting degradation of the transcription factors Ikaros and Aiolos, which affect leukocyte development and autoimmunity, is being evaluated for the treatment of systemic lupus erythematosus (SLE). METHODS: In this phase 2 trial, we randomly assigned patients in a 2:2:1:2 ratio to receive oral iberdomide (at a dose of 0.45, 0.30, or 0.15 mg) or placebo once daily for 24 weeks, in addition to standard medications. The primary end point at week 24 was a response on the SLE Responder Index (SRI-4), which was defined as a reduction of at least 4 points in the Systemic Lupus Erythematosus Disease Activity Index 2000 score (a 24-item weighted score of lupus activity that ranges from 0 to 105, with higher scores indicating greater disease activity), no new disease activity as measured on the British Isles Lupus Assessment Group 2004 index, and no increase of 0.3 points or more in the Physician's Global Assessment score (on a visual-analogue scale ranging from 0 [no disease activity] to 3 [maximal disease]). RESULTS: A total of 288 patients received the assigned intervention: 81 received iberdomide at a dose of 0.45 mg, 82 received iberdomide at a dose of 0.30 mg, 42 received iberdomide at a dose of 0.15 mg, and 83 received placebo. At week 24, the percentages of patients with an SRI-4 response were 54% in the iberdomide 0.45-mg group, 40% in the iberdomide 0.30-mg group, 48% in the iberdomide 0.15-mg group, and 35% in the placebo group (adjusted difference between the iberdomide 0.45-mg group and the placebo group, 19.4 percentage points; 95% confidence interval, 4.1 to 33.4; P = 0.01), with no significant differences between the groups that received the lower doses of iberdomide and the group that received placebo. Iberdomide-associated adverse events included urinary tract and upper respiratory tract infections and neutropenia. CONCLUSIONS: In this 24-week, phase 2 trial involving patients with SLE, iberdomide at a dose of 0.45 mg resulted in a higher percentage of patients with an SRI-4 response than did placebo. Data from larger, longer trials are needed to determine the efficacy and safety of iberdomide in SLE. (Funded by Bristol Myers Squibb; ClinicalTrials.gov number, NCT03161483; EudraCT number, 2016-004574-17.).

Biological impact of iberdomide in patients with active systemic lupus erythematosus.

OBJECTIVES: Iberdomide is a high-affinity cereblon ligand that promotes proteasomal degradation of transcription factors Ikaros (IKZF1) and Aiolos (IKZF3). Pharmacodynamics and pharmacokinetics of oral iberdomide were evaluated in a phase 2b study of patients with active systemic lupus erythematosus (SLE). METHODS: Adults with autoantibody-positive SLE were randomised to placebo (n=83) or once daily iberdomide 0.15 mg (n=42), 0.3 mg (n=82) or 0.45 mg (n=81). Pharmacodynamic changes in whole blood leucocytes were measured by flow cytometry, regulatory T cells (Tregs) by epigenetic assay, plasma cytokines by ultrasensitive cytokine assay and gene expression by Modular Immune Profiling. RESULTS: Iberdomide exhibited linear pharmacokinetics and dose-dependently modulated leucocytes and cytokines. Compared with placebo at week 24, iberdomide 0.45 mg significantly (p<0.001) reduced B cells, including those expressing CD268 (TNFRSF13C) (-58.3%), and plasmacytoid dendritic cells (-73.9%), and increased Tregs (+104.9%) and interleukin 2 (IL-2) (+144.1%). Clinical efficacy was previously reported in patients with high IKZF3 expression and high type I interferon (IFN) signature at baseline and confirmed here in those with an especially high IFN signature. Iberdomide decreased the type I IFN gene signature only in patients with high expression at baseline (-81.5%; p<0.001) but decreased other gene signatures in all patients. CONCLUSION: Iberdomide significantly reduced activity of type I IFN and B cell pathways, and increased IL-2 and Tregs, suggesting a selective rebalancing of immune abnormalities in SLE. Clinical efficacy corresponded to reduction of the type I IFN gene signature. TRIAL REGISTRATION NUMBER: NCT03161483.

Plasma micro-RNA-22 is associated with disease activity in well-established rheumatoid arthritis.

OBJECTIVES: Micro-RNAs (miRNAs) are an endogenous small, single-stranded, non-coding RNAs with a 18-25 nucleotide long and have been reported as potential extracellular biomarkers of various diseases. They mainly decrease the gene expression by inhibiting the translation or cause mRNA destabilisation. The aim of our study was to identify miRNAs whose concentration may be associated with severity of rheumatoid arthritis (RA). METHODS: A total of 74 unrelated individuals, 50 with RA and 24 in a control group were enrolled to the study. Real-time PCR was used to evaluate the plasma concentration levels of 8 miRNAs: miR-26a, miR-125b, miR-20b, miR-22, miR-221, miR-17, miR-93, miR-106b. RESULTS: The logistic regression results showed that miR-22 (p=0.0003) and miR-26a (p=0.049) may be the most important molecules distinguishing RA patients and healthy controls. Moreover, the quantity of miR-22 was different between rheumatoid factor (RF)-positive and RF-negative patients (p=0.04). CONCLUSIONS: In this study we demonstrated for the first time that plasma concentration of miR-22 may be considered as a potential molecular marker associated with disease activity.

The relationship of ADAMTSL2 and LRPAP1 gene methylation level with rheumatoid arthritis activity.

OBJECTIVES: The role of epigenetic mechanisms in the pathogenesis and course of RA as well as response to treatment is increasingly being emphasised. The aim of our study was to determine the ADAMTSL2 and LRPAP1 gene methylation levels in RA patients' serum divided according to disease activity and in comparison with the results with the control group. METHODS: Quantitative real-time methylation-specific PCR was used to analyse the methylation status of the investigated genes. RESULTS: We observed a significant difference in the methylation levels of both the ADAMTSL2 and the LRPAP1 genes in patients with high RA activity compared to patients in remission. CONCLUSIONS: ADAMTSL2 methylation status was inversely correlated with DAS28. High disease activity was associated with lower methylation levels than in remission as well as in the control group. Different results were obtained for the methylation levels of the LRPAP1 gene. High disease activity and the control group were characterised by a higher level of LRPAP1 gene methylation compared to patients in remission. We have proven that methylation may play an important role in the course and severity of RA. The level of ADAMTSL2 and LRPAP1 gene methylation might impact the development of disease and reflect the activity of RA.

Respiratory involvement in antineutrophil cytoplasmic antibody-associated vasculitides: a retrospective study based on POLVAS registry.

OBJECTIVES: The study aimed to characterise the Polish population of (ANCA)-associated vasculitides (AAV) with respiratory involvement (RI), in comparison to the subgroup without lung manifestations and the other cohorts. METHODS: Retrospective analysis of the Polish population of AAV with RI was conducted, based on data from the POLVAS registry. Standard descriptive statistics, χ2 test, and Mann-Whitney U test were used to perform comparisons. RESULTS: Among 461 cases qualified to this study, there were 316 cases with RI (68.5%), 206 with granulomatosis with polyangiitis (GPA) (65.2%), 80 with eosinophilic granulomatosis with polyangiitis (EGPA) (25.3%) and 30 with microscopic polyangiitis (MPA) (9.5%). Proportion of RI in GPA, MPA, and EGPA accounted for 67.8%; 40.0%; 97.6%, respectively. The number of relapses was higher in the RI group (median 1.0 vs. 0.0; p=0.01). In the subgroup of combined GPA and MPA with RI, the trends toward higher proportion of deaths (11.7% vs. 5.7%; p=0.07), relapses requiring hospitalisation (52.2% vs. 42.4%, p=0.07) and relapses requiring admission to the intensive care unit (5.6% vs. 1.4%, p=0.09) were observed, median maximal concentration of CRP was higher (46 vs. 25 mg/l; p=0.01) and more aggressive treatment was administered. CONCLUSIONS: Prevalence of RI in the Polish population of AAV is similar to the values reported in the literature, however, the proportion observed in GPA is closer to those presented in Asian than Western European cohorts. RI seems to be associated with a more severe course of disease and its presence prompts more aggressive treatment.

Serum Calprotectin - a NET Product - as a Biomarker of Disease Activity in Patients with Systemic Lupus Erythematosus: A Single-Center Case-Control Study from Poland.

BACKGROUND Calprotectin (S100A8/A9 or myeloid-related protein 8/14) is a heterodimeric S100 complex expressed in leukocytes. Calprotectin participates in development of the inflammatory response by binding to receptors for advanced glycation end-products (RAGE) and Toll-like receptors (TLR). The clinical activity of systemic lupus erythematosus (SLE) is evaluated using the Systemic Lupus International Collaborating Clinics (SLICC) criteria and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). This Polish single-center case-control study aimed to evaluate serum levels of calprotectin as a rapid diagnostic biomarker of SLE (59 patients with SLE were compared with 52 healthy controls). MATERIAL AND METHODS Calprotectin concentration was measured with the use of enzyme-linked immunosorbent assay (ELISA). The SLE activity of the patients was assessed by the SLEDAI scale. Statistical analysis of the results was carried out using MedCalc 15.8 software. P<0.05 was considered statistically significant. RESULTS A significantly higher concentration of calprotectin was found in the study group compared to the control group (medians: 3.11 vs 2.45 ng/ml; P=0.0013). We found that calprotectin has high sensitivity (89.83%) and specificity (53.85%) in differentiating between SLE patients and healthy volunteers. We found that calprotectin has very high sensitivity (100%) and specificity (82.46%) in detection of patients with moderate and severe SLE assessed using SLEDAI. CONCLUSIONS Consistent with previous studies, serum calprotectin level was revealed to have potential as a rapid diagnostic biomarker of disease activity in patients with SLE.

Methods of assessment of joint involvement in various systemic connective tissue diseases.

Joint involvement is one of the most common clinical manifestations of systemic connective tissue diseases (CTD). Joint symptoms can take various forms, ranging from joint pain to mono-arthritis or symmetrical poly-arthritis. In most cases, arthritis takes a non-destructive form, such as in the course of systemic lupus erythematosus or primary Sjögren's syndrome, to destructive arthritis in overlap syndromes of CTD with rheumatoid arthritis. In addition, apart from the wide variety of forms of joint involvement, it should be noted that joint symptoms may be one of the domains suggesting a severe course of the disease. The study attempts to present the methods of assessing the involvement of the locomotor system. The search for appropriate scales to determine the degree of joint involvement is important in assessing the severity of joint changes, has an impact on the overall degree of disease activity, and allows for timely implementation of appropriate treatment.

Arterial hypertension in systemic sclerosis.

Introduction: Arterial hypertension (AH) is common in systemic connective tissue diseases. Aim: To evaluate the incidence of AH in patients with systemic sclerosis (SSc) and to present clinical characteristics of the group diagnosed with AH. Material and methods: The study involved 108 patients with SSc divided into two groups: with AH (+) - 45 and AH (-) - 63. Moreover, the serological profile, scleroderma renal crisis, involvement of internal organs and mortality were determined. The kidney function was assessed based on creatinine concentration and the estimated glomerular filtration rate (eGFR). Results: AH was diagnosed in 47/108 SSc patients (41.7%). The age difference among patients was statistically significant and was higher in the AH (+) SSc group (p = 0.026). The incidences of oesophageal involvement (p = 0.011), digital ulcerations (p = 0.017), and mortality (p = 0.019) were found to be significantly higher in the AH (+) SSc group. Scleroderma renal crisis was observed in 9/108 patients (8.3%). The incidence of chronic kidney disease (CKD) was higher in the AH (+) SSc group, both of stage 2 (p = 0.013) and 3 (p = 0.07). Stages 4 and 5 of CKD were found only in the group with AH. Moreover, this group had a higher incidence of elevated uric acid (p = 0.007). Conclusions: AH is relatively common in patients with SSc and is associated with a significantly more severe course of the disease and higher frequency of renal involvement.

Subphenotypes of ANCA-associated vasculitis identified by latent class analysis.

OBJECTIVES: ANCA-associated vasculitides (AAV) are a heterogeneous group of rare diseases with unknown aetiology and the clinical spectrum ranging from life-threatening systemic disease, through single organ involvement to minor isolated skin changes. Thus, there is an unmet need for phenotype identification, especially among patients with granulomatosis with polyangiitis (GPA). Patients with microscopic polyangiitis (MPA) seem to be clinically much more uniform. Recently, three subcategories of AAV have been proposed and described as non-severe AAV, severe PR3-AAV, and severe MPO-AAV. METHODS: In line with these attempts, we decided to use an unbiased approach offered by latent class analysis (LCA) to subcategorise GPA and MPA in a large cohort of Polish AAV patients included in a multicentre POLVAS registry. RESULTS: LCA of our AAV group identified a four-class model of AAV, including previously proposed three subphenotypes and revealing a fourth (previously not described) clinically relevant subphenotype. This new subphenotype includes only GPA patients, usually diagnosed at a younger age as compared to other groups, and characterised by multiorgan involvement, high relapse rate, relatively high risk of death, but no end-stage kidney disease. CONCLUSIONS: Based on multiple clinical and serological variables, LCA methodology identified 4-class model of AAV. This newly described fourth class of AAV may be of clinical relevance and may require prompt diagnosis and aggressive treatment due to the multiorgan involvement, high risk of relapse and marked mortality among these relatively young GPA subjects.

Sicca syndrome in the same family - the importance of anti-Ro60, anti-Ro52 and anti-La antibody profiling in Sjögren's syndrome.

Sicca syndrome, which is typical for Sjögren's syndrome (SS), both primary (pSS) and secondary (sSS), is relatively often comorbid with other autoimmune diseases. The current classification criteria for SS published in 2016 include only anti-SSA (anti-Ro) autoantibody, while the latest literature proposes that anti-Ro60/anti-Ro52 autoantibody profiles should be used instead, as these two types of antibodies correlate with specific clinical symptoms and laboratory test findings. The paper presents the case of a 41-year-old woman suffering from pSS and her three daughters, who were under observation for rheumatic disorders due to sicca symptoms, especially pSS, as well as a discussion on separate determination of anti-Ro60 and anti-Ro52 autoantibodies based on current literature in the PubMed database. When testing with antinuclear antibodies, the Ro60+Ro52+La+ autoantibody profile most closely matches for pSS. Further research is needed to find marker antibodies for SS and quantification methods.

Differential approach to peripheral blood cell ratios in patients with systemic lupus erythematosus and various manifestations.

New markers of systemic lupus erythematosus (SLE) activity are under investigation. In recent years, the researchers have been focusing increased attention on the role of haematological indicators in assessing the disease activity. Specifically, neutrophil-, basophil-, eosinophil-, monocyte- and platelet-to-lymphocyte ratios (NLR, BLR, ELR, MLR and PLR) have been considered. The specific objective of this study was to determine the suitability of the haematological markers for the assessment of SLE activity and SLE-related organ damage. This study is a retrospective analysis of 136 patients with SLE (124 women and 12 men) who received chloroquine/hydroxychloroquine (HQ/HCQ) monotherapy or HQ/HCQ therapy combined with low/medium doses of glucocorticoid. All patients were assessed for disease activity using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scale. In addition, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) inflammatory parameters were determined in each patient. NLR, BLR, ELR, MLR and PLR were evaluated and correlated with the SLE activity parameters and inflammatory markers. The mean values of the haematological indicators were compared in particular manifestations of SLE-induced organ damage. For numerical variables, descriptive statistics were calculated: median, standard deviation, minimum and maximum values. The Mann-Whitney U test was used for the comparison of continuous variables in the two groups. The Spearman rank correlation test was used to search for any relationships between variables. A p value < 0.05 was considered to be statistically significant. We have found a positive correlation between ELR, MLR and the SLEDAI scale (r = 0.22 and r = 0.27, respectively). NLR, MLR and PLR ratios were significantly correlated with ESR and CRP. Considerably higher NLR values were found in patients with cutaneous and/or mucosal symptoms and with kidney involvement compared to patients without such involvement (4.26 ± 4.2 vs 3.27 ± 2.7; p = 0.05 and 5.45 ± 5.6 vs 3.05 ± 2.0; p < 0.001 respectively). BLR and MLR were significantly higher in patients manifesting symptoms of vasculitis (0.09 ± 0.1 vs 0.02 ± 0.01; p < 0.001 and 3.1 ± 4.2 vs 0.3 ± 0.1; p < 0.001 respectively), arthritis and/or myositis (0.04 ± 0.09 vs 0.02 ± 0.01; p = 0.01 and 1.02 ± 2.6 vs 0.35 ± 0.4; p = 0.01 respectively), whereas elevated ELR ratios were observed in patients with vasculitis (0.4 ± 0.5 vs 0.08 ± 0.06; p < 0.001) compared to patients without such organ involvement. The PLR marker was substantially higher in patients exhibiting haematological disorders in the course of SLE (276.6 ± 226.4 vs 192.6 ± 133.5; p = 0.01). The results indicate that ELR and MLR are effective markers of SLE activity. The haematological indicators may predict SLE-dependent organ damage, particularly cutaneous, mucosal, arthritic, myositic, haematological and kidney involvement.

Clinical and serological parameters of progression and prognosis in patients with systemic sclerosis - a state of the art review.

OBJECTIVE: Systemic sclerosis (SSc) is a multi-organ connective tissue disease that leads to the dysfunction and the impaired morphology of blood vessels due to non-specific inflammation and progressive fibrosis. Due to the diversity of SSc and even though the factors predisposing to the severe course of SSc are known, it is not always possible to predict the disease progression and to determine the prognosis. Ideally, the group of patients with faster progression of organ lesions and a worse course of the disease should be identified and the early intensive treatment should be instituted. The aim of the article, is an attempt to identify the factors that worsen the prognosis in the course of SSc. The analysis of numerous studies demonstrated that patients with short-lasting SSc, with the presence of anti-RNA polymerase III antibodies, with a generalized type of SSc with quickly progressing skin lesions and males should be most strictly monitored. Moreover, vascular complications, tendon ruptures and fast capillaries loss observed in nailfold capillaroscopy are the factors deteriorating the prognosis in SSc. CONCLUSION: In conclusion, despite the known, the factors that worsen the prognosis, it is difficult to predict the course of systemic sclerosis. Due to its incompletely elucidated etiopathology as well as the diverse and unpredictable nature of the disease, reliable markers to determine the prognosis in SSc have not been found.

Haematological abnormalities in systemic sclerosis.

Systemic sclerosis (SSc) is a connective tissue disease characterised by extremely high heterogeneity. This heterogeneity concerns the organ involvement, course of disease and prognosis. Unlike in some other systemic connective tissue diseases, especially systemic lupus erythematosus, in SSc haematological disorders occur rarely. When they develop, they affect erythrocytes, leucocytes and platelets. The most common cause of this pathology of erythrocyte abnormalities is microcytic anaemia resulting from micro-haemorrhages with telangiectasias within the digestive mucosa in patients with SSc. In SSc patients with severe haematological disturbances, the differential diagnosis should include overlapping with another systemic connective tissue disease or a haemato-oncological disease (lympho/myeloproliferative syndrome). In SSc patients with monoclonal proteins or cryoglobulins, it is essential to consider a haemato-oncological disease. In such cases, the differential diagnosis should be focused on a paraneoplastic syndrome, especially when the haematological symptoms develop shortly after the diagnosis of SSc and in the elderly.

Clinical consequences of the presence of anti-RNA Pol III antibodies in systemic sclerosis.

INTRODUCTION: Anti-RNA polymerase III (a-RNA Pol III) antibodies are marker antibodies in patients with systemic sclerosis (SSc). AIM: To assess the prevalence of a-RNA Pol III in patients with SSc and to identify the differences in the disease picture in SSc patients with and without a-RNA Pol III antibodies. MATERIAL AND METHODS: The study was performed in 126 SSc patients. The subtype of SSc, incidence of internal organ involvement, malignancy, death and serological profiles were determined in the entire group. The study groups were studied according to the presence of antibodies by applying the commercial test - EUROLINE SSc Profile. Due to the presence of a-RNA Pol III, patients were divided into two groups: the a-RNA Pol III (+) SSc group of 19 patients and the a-RNA Pol III (-) SSc group of 107 patients. RESULTS: A-RNA Pol III were present in 19/126 patients with SSc (15%), 13/19 (68.4%) patients had no other SSc marker antibodies. A-RNA Pol III were more common in patients with diffuse cutaneous SSc (p = 0.049). We showed a significant positive association between a-RNA Pol III and occurrence of malignancy (p = 0.007), scleroderma renal crisis (p = 0.001) and decreased DLCO (p = 0.007). CONCLUSIONS: Anti-a-RNA Pol III antibodies are common in patients with SSc, particularly with a diffuse subtype. In more than 50% of patients with a-RNA Pol III antibodies, they may be present as the sole marker of antibodies. In SSc, a-RNA Pol III antibodies are frequently associated with malignancy occurrence, kidney and lung involvement.

Nephrotic syndrome in the course of type 1 diabetes mellitus and systemic lupus erythematosus with secondary antiphospholipid syndrome - diagnostic and therapeutic problems.

Nephrotic syndrome (NS) can be a symptom of many autoimmune, metabolic, or infectious diseases. Kidney involvement is often observed in the course of diabetes mellitus (DM) and systemic lupus erythematosus (SLE). The development of NS with coexisting SLE and DM generates serious diagnostic problems. In this paper, the authors present diagnostic and therapeutic dilemmas in a patient with long-lasting DM, SLE, and secondary antiphospholipid syndrome, in whom NS symptoms appeared. Histopathological examination of the kidney confirmed the diagnosis of lupus nephritis. Immunosuppressive and anticoagulant drugs were used. The authors demonstrated that the character of morphologic lesions in the kidney biopsy can help in diagnosis, nephropathy classification, and further therapeutic decisions, which are distinct in both diseases.

Urticarial rash, fever, and arthritis: A case of refractory Adult-onset Still's disease with good response to tocilizumab.

Adult-onset Still's disease (AOSD) is a rare, systemic inflammatory disorder of not completely understood etiology. Aberrant activation of the innate immune system and overproduction of several pro-inflammatory mediators are considered a critical component in disease pathogenesis. AOSD still poses a challenge due to the broad range of differential diagnoses and no specific biomarkers. Four cardinal symptoms are quotidian spiking fever, joint involvement, evanescent salmon pink-rash rash, and leukocytosis with neutrophilia. We present a case of a 61-year-old female with a recurrent urticarial rash accompanied by attacks of high fever, tender joints, sore throat, enlarged liver, elevated inflammatory reactants, and hyperferritinemia. After an extensive workup, the patient fulfilled the criteria of AOSD. She was refractory to the glucocorticosteroids and disease-modifying anti-rheumatic drugs (DMARDs). Finally, after several unsuccessful attempts to achieve disease control with traditional DMAR's administration of Tocilizumab (TCZ), a humanized anti-IL-6 receptor antagonist resulted in substantial disease improvement. Since skin manifestations are a common feature of AOSD, it should be among differential diagnoses in patients with skin lesions and constitutional symptoms. Biologic agents represent a significant therapeutic advance in patients with AOSD refractory to conventional therapy.

Factors associated with quality of life in systemic sclerosis: a cross-sectional study.

INTRODUCTION: Systemic sclerosis (SSc) is a connective tissue disease characterized by progressive fibrosis of the skin and internal organs, leading to their failure and disturbances in the morphology and function of blood vessels. The disease affects people in different ways, and identifying how the difficulties and limitations are related to quality of life may contribute to designing helpful interventions. The aim of this study was to identify factors associated with quality of life in people with SSc. METHODS: This was a cross-sectional study conducted in 11 rheumatic centres in Poland. Patients diagnosed with SSc were included. Quality of life was measured using the SSc Quality of Life Questionnaire (SScQoL). The following candidate factors were entered in preliminary multivariable analysis: age, place of residence, marital status, occupational status, disease type, disease duration, pain, fatigue, intestinal problems, breathing problems, Raynaud's symptoms, finger ulcerations, disease severity, functional disability, anxiety and depression. Factors that achieved statistical significance at the 10% level were then entered into a final multivariable model. Factors achieving statistical significance at the 5% level in the final model were considered to be associated with quality of life in SSc. RESULTS: In total, 231 participants were included. Mean age (SD) was 55.82 (12.55) years, disease duration 8.39 (8.18) years and 198 (85.7%) were women. Factors associated with quality of life in SSc were functional disability (ß = 2.854, p < 0.001) and anxiety (ß = 0.404, p < 0.001). This model with two factors (functional disability and anxiety) explained 56.7% of the variance in patients with diffuse SSc and 73.2% in those with localized SSc. CONCLUSIONS: Functional disability and anxiety are significantly associated with quality of life in SSc. Interventions aimed at improving either of these factors may contribute towards improving the quality of life of people with SSc.

[Late-onset sjögren's syndrom].

Sjögren's syndrome is a systemic autoimmune disease characterized by exocrine glands damage, resulting in the development of dry eyes and dry mouth, as well as extraglandular manifestation. It usually starts between the ages of 30 and 50. Late-onset Sjögren's syndrome should be considered as a disease that appears after age 65, but the literature also reports of the age 50, 60, or even 70. The prevalence of late-onset Sjögren's syndrome is estimated about 20%. The course of late-onset Sjögren's syndrome may differ when compared with patients with a younger onset. Lack of sicca symptoms and marker antibodies may be associated with a delay in Sjögren's syndrome diagnosis. Particularly in the elderly, the occurrence of sicca symptoms may be considered as age-related and medication-related.

Reasons for diagnostic delays of axial spondyloarthritis.

OBJECTIVE: Introduction: The probability of development of axial spondyloarthritis (axSpA) is estimated to be above 90% among patients with chronic back pain, presence of HLA B27 antigen and positive family history of ankylosing spondylitis (AS), psoriasis, reactive arthritis, inflammatory bowel disease or uveitis. The nonradiographic axSpA and ankylosing spondylitis diseases' activity has a comparable impact on the patients' quality of life and from the practical point of view the approach to treatment of each of them is the same. The aim: The attempt to identify the reasons of diagnostic delays of AS among patients hospitalized in the Rheumatology and Connective Tissue Diseases Department in Lublin and to suggest the ways of improving the accuracy of diagnostic track among other healthcare providers than rheumatologists. PATIENTS AND METHODS: Material and methods: We performed a retrospective analysis of the records of 82 patients' with the established diagnosis of AS, hospitalized in the Rheumatology and Connective Tissue Diseases Department in Lublin in 2000-2019, and of 45 years of age and older. RESULTS: Results: From among 82 patients (28 women and 54 men) the diagnosis of AS after 45 years of age was established in 25 patients (10 women and 15 men) - group t, and in the other 57 patients (group n) the diagnosis was established before 45 years of age. On average the age at the time of diagnosis in the whole group (t+n) was 40,7±10,2 (18-76) years, the age at the beginning of inflammatory back pain (age of axial symptoms) was 30,9±8,5 (13-51) years and the diagnostic delay (period between first axial symptoms and diagnosis establishment) was 9,75±9,5 (0-46) years. We did not find any statistically significant associations between sex and age at the moment of diagnosis, age of the beginning of axial symptoms and the time of diagnostic delay. There was no significant difference of incidence of enthesitis, uveitis, arthritis, prevalence of family history of spondyloarthritis and CRP level between group t and n. Antigen HLA B27 was more frequently present in group t. CONCLUSION: Conclusions: Instead of the recognition progress and worldwide popularization of knowledge about axSpA, the diagnostic delays in this field are still estimated to last many years, the patients are looking for other specialists' help, and they can be not knowledgeable of the inflammatory back pain criteria. Currently, HLA B27 antigen and C-reactive protein are the two most commonly used biomarkers for diagnostic and disease activity monitoring purposes of axSpA and magnetic resonance is the only "imaging biomarker". The presence of extra-axial symptoms does not improve the diagnostic sensitivity.

[Uwarunkowania opóznienia rozpoznan osiowych spondyloartropatii zapalnych].

OBJECTIVE: Wstep: Prawdopodobienstwo rozwoju osiowej postaci spondyloartropatii zapalnej (axSpA) wynosi ponad 90% u chorych z przewleklym bólem kregoslupa, obecnym antygenem HLA B27 i dodatnim wywiadem rodzinnym w kierunku zesztywniajacego zapalenia stawów kregoslupa (ZZSK), luszczycy, reaktywnego zapalenia stawów, chorób zapalnych jelit lub zapalenia blony naczyniowej oka. Aktywnosc choroby w postaci nieradiologicznej axSpA i ZZSK podobnie wplywa na jakosc zycia a z praktycznego punktu widzenia podejscie do leczenia jest jednakowe. Cel pracy: Próba identyfikacji przyczyn spóznionych rozpoznan ZZSK wsród chorych hospitalizowanych w Klinice Reumatologii i Ukladowych Chorób Tkanki Lacznej w Lublinie oraz sugestie dotyczace poprawy sciezki diagnostycznej, zwlaszcza wsród lekarzy innych specjalnosci niz reumatolodzy. PATIENTS AND METHODS: Material i metody: Retrospektywnej analizie poddano historie chorób 82 pacjentów z ustalonym rozpoznaniem ZZSK hospitalizowanych w Klinice Reumatologii i Ukladowych Chorób Tkanki Lacznej w Lublinie w latach 2000-2019, którzy ukonczyli 45. rok zycia. RESULTS: Wyniki: Sposród 82 chorych (28 kobiet i 54 mezczyzn) rozpoznanie ZZSK po 45. roku zycia postawiono u 25 chorych (10 kobiet i 15 mezczyzn) - grupa t (30,4%), u pozostalych 57 chorych (grupa n) rozpoznanie ustalono przed 45. rokiem zycia. Sredni wiek w chwili rozpoznania w calej grupie (t+n) wynosil 40,7±10,2 (18-76) roku, wiek, w którym pojawil sie zapalny ból kregoslupa (wiek objawów osiowych) wynosil 30,9±8,5 (13-51) roku a opóznienie rozpoznania (okres od pojawienia sie objawów osiowych do ustalenia rozpoznania) 9,7±9,5 (0-46) roku. Nie stwierdzono istotnych statystycznie zaleznosci miedzy plcia a wiekiem w chwili rozpoznania, wiekiem pojawienia sie objawów osiowych i opóznieniem rozpoznania. Nie zaobserwowano istotnych zaleznosci miedzy czestoscia wystepowania zapalenia przyczepów sciegnistych, blony naczyniowej oka, stawów obwodowych, chorób z kregu spondyloartropatii zapalnych w rodzinie oraz stezenia CRP miedzy grupa t i n. Antygen HLA B27 czesciej obecny byl w grupie t. CONCLUSION: Wnioski: Mimo postepu w diagnostyce i wiekszego upowszechniania wiedzy na temat spondyloartropatii zapalnych, opóznienia w rozpoznaniu tych chorób sa wieloletnie, poniewaz pacjenci bardzo czesto poszukuja pomocy u innych specjalistów, którzy moga byc niezaznajomieni z kryteriami bólu zapalnego kregoslupa. W chwili obecnej jedynymi biomarkerami wykorzystywanymi w diagnostyce i monitorowaniu aktywnosci spondyloartropatii zapalnych jest odpowiednio obecnosc antygenu HLA B27 i stezenie CRP a jedynym "biomarkerem obrazowym" jest rezonans magnetyczny. Wystepowanie objawów pozaosiowych nie poprawia czulosci diagnostycznej.