Usefulness in daily practice of the Systemic Lupus Erythematosus Disease Activity Index 2000 scale and the Systemic Lupus Erythematosus Disease Activity Score index for assessing the activity of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by high heterogeneity of clinical manifestations and an uncertain prognosis. Although the mortality rate due to SLE has decreased significantly in recent decades, there is still a need to find good tools to measure disease activity for early detection of exacerbations and treatment planning. Over the decades, more than a dozen disease activity scales/indicators have been developed, with the SLE Disease Activity Index (SLEDAI) being the most popular. More recently, the new SLE Disease Activity Score (SLE-DAS) has been introduced. This paper compares the two methods of assessing SLE activity, and presents the relevance of these scales in pregnant SLE patients and their use in formulating definitions of remission and low disease activity. The results show that the SLEDAI and the SLE-DAS are of comparable value in assessing SLE activity and complement each other.

The usefulness of nailfold capillaroscopy in scleroderma-spectrum disorders: a single-centre observational study.

Introduction: Nail-fold capillaroscopy is a non-invasive method for assessment of the microcirculation in nail folds. This examination is particularly useful for diagnosis, assessment of activity, evaluation of the response to treatment, and assessment of the correlation of changes in microvessels with changes in organs in systemic sclerosis and in scleroderma-spectrum diseases, i.e. dermatomyositis, polymyositis, mixed connective tissue disease, and undifferentiated connective tissue disease. Aim: To perform capillaroscopic analyses of lesions in patients with scleroderma-spectrum diseases and determine the correlation of the capillaroscopic image with organ manifestations and the serological profile. Material and methods: The study involved 15 patients with scleroderma-spectrum disorders. Results: Mixed systemic connective tissue disease was diagnosed in 8 patients, and dermatomyositis was detected in 7 patients. The study assessed the frequency of clinical symptoms, e.g. interstitial lung disease or arthritis, and the presence of ANA antibodies. Scleroderma-like microangiopathy was diagnosed in 47% of patients with scleroderma-spectrum disorders. The early pattern was found in patients with mixed systemic connective tissue disease, whereas dermatomyositis was characterized by the late pattern. Non-specific changes were found in 27% of the patients, and a normal image was observed in 27% of the patients. Conclusions: The analysis also revealed that the reduced number of vessels correlated with the occurrence of interstitial lung disease, and the incidence of Raynaud's phenomenon and arthritis was statistically significantly higher in patients with systemic connective tissue disease than in those with dermatomyositis.

Late-age onset systemic sclerosis-clinical and serological characteristics.

The clinical course and serological profile of the late-age onset systemic sclerosis (LAO SSc) and the early-age onset SSc (EAO SSc) was compared. The study enrolled 157 patients that fulfilled the American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) classification criteria for systemic sclerosis (SSc). Among them, 69 had diffuse cutaneous SSc (dcSSc) and 88 limited cutaneous SSc (lcSSc). Within this population, 39 patients developed the disease over the age of 60 years old (LAO SSc) and 118 prior to that age (EAO SSc). The subtype of SSc, the incidence of internal organ involvement, the prevalence of malignancy, mortality, and serological profile were compared between both groups. The LAO SSc was observed in 39 of total 157 patients with SSc and exhibited a notably higher prevalence of pulmonary arterial hypertension (p = 0.014), heart involvement (p = 0.0014), and renal involvement (p = 0.0002). The occurrence of arthralgias was less common in the LAO SSc group (p = 0.02) than in the EAO SSc group. Furthermore, in the LAO SSc group, the prevalence of anti -RNA polymerase III antibodies (p = 0.008) and antiPM/Scl antibodies (p = 0.048) were significantly lower than in the EAO SSc group. On the other hand, higher anti-Th/To antibody levels (p = 0.014) were recorded in the LAO SSc group. Approximately 25% of SSc patients experienced a delayed onset of the disease after the age of 60 years old. Some clinical and serological features of late-onset SSc were markedly different from that in early-onset disease. Particularly noteworthy is the fact that involvement of internal organs such as heart and kidneys, as well as pulmonary arterial hypertension were much more often observed among patients with LAO SSc which in our suggestion may be referred to age-related co-morbidities. Key Points • Significant differences in clinical and serological profile of the disease were found between late-age onset (LAO) and early-age onset (EAO) SSc. • Incidence of dcSSc as well as prevalence of anti-RNA polymerase III and anti-PM/Scl antibodies were found to be lower in patients over 60 years old compared to those before 60, but regardless of the age of the disease onset. • Internal organ morbidity, notably pulmonary arterial hypertension, renal impairment and heart disease were significantly more common in elder SSc patients as well as in those with late disease onset. • These findings may suggest an impact of age-related co-morbidities on the course of late-age onset SSc.

Clinical Characteristics of EGPA Patients in Comparison to GPA Subgroup with Increased Blood Eosinophilia from POLVAS Registry.

Objective: To characterize the eosinophilic granulomatosis with polyangiitis (EGPA) population from the POLVAS registry depending on ANCA status and diagnosis onset, including their comparison with the granulomatosis with polyangiitis (GPA) subset with elevated blood eosinophilia (min. 400/µl) (GPA HE) to develop a differentiating strategy. Methods: A retrospective analysis of the POLVAS registry. Results: The EGPA group comprised 111 patients. The ANCA-positive subset (n = 45 [40.54%]) did not differ from the ANCA-negative one in clinics. Nevertheless, cardiovascular manifestations were more common in ANCA-negative patients than in those with anti-myeloperoxidase (MPO) antibodies (46.97% vs. 26.92%, p = 0.045). Patients diagnosed before 2012 (n = 70 [63.06%]) were younger (median 41 vs. 49 years, p < 0.01), had higher blood eosinophilia at diagnosis (median 4,946 vs. 3,200/µl, p < 0.01), and more often ear/nose/throat (ENT) and cardiovascular involvement. GPA HE comprised 42 (13.00%) out of 323 GPA cases with reported blood eosinophil count. Both GPA subsets had a lower prevalence of respiratory, cardiovascular, and neurologic manifestations but more often renal and ocular involvement than EGPA. EGPA also had cutaneous and gastrointestinal signs more often than GPA with normal blood eosinophilia (GPA NE) but not GPA HE. The model differentiating EGPA from GPA HE, using ANCA status and clinical manifestations, had an AUC of 0.92, sensitivity of 96%, and specificity of 95%. Conclusion: Cardiovascular symptoms were more prevalent in the ANCA-negative subset than in the MPO-ANCA-positive one. Since EGPA and GPE HE share similarities in clinics, diagnostic misleading may result in an inappropriate therapeutic approach. Further studies are needed to optimize their differentiation and tailored therapy, including biologics.

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.

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.

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.

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.

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.).

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.

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.

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.

Systemic Inflammatory Parameters in Patients with Elderly-Onset Rheumatoid Arthritis (EORA) and Young-Onset Rheumatoid Arthritis (YORA)-An Observational Study.

BACKGROUND: Rheumatoid arthritis (RA) occurs more often in elderly individuals. Elderly onset RA (EORA) (onset > 60 years) encompasses a specific subset of patients if compared with young onset RA (YORA) (onset at a younger age). There is a need to define reliable, simple markers to properly assess the inflammatory activity of RA. Hematological markers of systemic inflammation (Platelet-To-Lymphocyte (PLR) and Neutrophil-To-Lymphocyte (NLR) ratios) are novel measures of the inflammatory response. The goal of the study was to analyze the course of EORA vs. YORA patients and to assess associations between systemic and clinical disease activity markers, including PLR and NLR, in different subsets of patients. PLR and NLR have not previously been assessed in EORA and YORA. METHODS: The study group consisted of 113 consecutive patients (63 EORA and 50 YORA). The following assessments were performed: joint counts, Disease Activity Score (DAS28), complete blood cell counts, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). RESULTS: EORA was characterized by significantly higher disease activity markers (conventional inflammatory and clinical), a lower rate of remission or low disease activity, and less frequent use of biological drugs and glucocorticoids. The NLR and PLR were positively correlated with disease activity markers. The PLR was significantly lower in EORA compared with in YORA. CONCLUSION: EORA and YORA patients differed significantly. In EORA, conventional disease activity markers were higher, the PLR was significantly lower.

The prevalence and significance of anti-PM/Scl antibodies in systemic sclerosis.

INTRODUCTION: Anti-PM/Scl (a-PM/Scl) antibodies are found in different systemic autoimmune diseases such as polymyositis, dermatomyositis, systemic sclerosis (SSc) and overlap syndromes. According to literature, they are detected in approx. 2% of SSc patients, but their presence is more common in SSc with myositis overlap. OBJECTIVE: The aim of the study was to assess the prevalence of a-PM/Scl in patients with SSc and to identify differences in the clinical profile of the disease in patients with the presence of a-PM/Scl. MATERIAL AND METHODS: The study was performed on 126 European Caucasian SSc patients (98 females and 28 males) hospitalized consecutively in the Department of Rheumatology and Connective Tissue Diseases. The study group was analyzed for the potential presence of a-PM/Scl using a commercial test - EUROLINE Systemic Sclerosis Profile. The detection and interpretation were carried out electronically using the specific Euroimmun - EUROLineScan programme. The subtype of SSc, incidence of internal organ involvement and serological profile were determined in the entire group. Due to the presence of a-PM/Scl, patients were divided into two groups: a-PM/Scl (+) SSc - 22 patients and a-PM/Scl (-) SSc - 104 patients. RESULTS: A-PM/Scl was detected in 22/126 patients with SSc (17.5%). A strong correlation was found between a-PM/Scl and myalgia or myositis (p = 0.0379), hand joints contractures (p = 0.0002) and the prevalence of overlap syndrome (p = 0.0142). There were no relationships between the presence of a-PM/Scl and subtypes of SSc, other organ involvement, digital ulcers or calcinosis. CONCLUSIONS: Anti-PM/Scl antibodies are fairly common in patients with systemic sclerosis. In SSc, anti-PM/Scl antibodies are frequently associated with myalgia or myositis, hand joint contractures and an overlap syndrome.

The value of anti-CarP and anti-PAD4 as markers of rheumatoid arthritis in ACPA/RF negative rheumatoid arthritis patients.

BACKGROUND: Anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF) are key factors in the American College of Rheumatology/European League Against Rheumatism rheumatoid arthritis (RA) classification criteria markers. However, about 30% of patients diagnosed with RA are seronegative, rationalizing the need for new serologic markers for RA. Antibodies against carbamylated proteins (anti-CarP) and against peptidyl-arginine deiminase type 4 (anti-PAD4) have been postulated to be useful RA markers. The purpose of this study is to evaluate the value of anti-CarP and anti-PAD4 in a well-characterized population of RA patients and healthy controls (HCs). METHODS: A total of 122 RA patients and 30 HCs were enrolled in the study. Serum levels of ACPA, anti-PAD4, anti-CarP and RF were determined by enzyme-linked immunosorbent immunoassays (ELISAs). Synthetic carbamylated peptides were used in the ELISA assay to determine the protein targets of the anti-CarP antibodies. RESULTS: Rates of ACPA, RF, anti-PAD4 and anti-CarP positivity were 85.2%, 67.2%, 55.7% and 46.7% in RA, and 0%, 0%, 6.7% and 6.7% in HC respectively. In the RA population, 25.4% of patients had all four types of antibodies positive, while 6.6% had no antibodies. There was a significant correlation between anti-PAD4 and ACPAs (r s = 0.39), RF and ACPAs, (r s = 0.3) and RF and anti-CarP, (r s = 0.3). There was no correlation between ACPAs and anti-CarP. Anti-CarP positivity was noted in 49 (47.1%) and 45 (54.9%) of ACPAs and RF positive patients respectively. In addition, five anti-CarP+ patients did not have ACPA nor RF. CONCLUSION: Anti-CarP but not anti-PAD4 may be a useful biomarker in identifying ACPA/RF negative RA patients. This antibody may identify an additional RA population who may benefit from early implementation of aggressive therapy.

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.

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.

ANCA-associated vasculitis patients treated in Polish intensive care units - retrospective characteristics based on the POLVAS registry.

INTRODUCTION: ANCA-associated vasculitides (AAV) is a group of rare disorders where inflammation and damage of the small blood vessels lead to dysfunction of the supplied organs. In severe flares of the disease patients may require intensive care unit (ICU) admission and treatment. The study aims to characterize Polish patients with AAV who were admitted to the ICU and compare them to the others. MATERIAL AND METHODS: An observational, retrospective study based on the POLVAS - registry of Polish adult patients with AAV was carried out. Patients admitted to the ICU (ICU group) were identified and compared with the patients who did not require ICU admission (non-ICU group). Characteristics and comparison between groups were made using standard statistic descriptive methods. RESULTS: 30 patients admitted to the ICU were identified among 573 cases included in the registry. All patients in the ICU group with available data were ANCA positive. The clinical manifestations related to the ICU admission were respiratory, renal and central nervous system involvement. The treatment regimen for remission induction was similar in both groups. Almost half of the patients in the ICU-group (48.3%) required dialysis, whereas in the non-ICU group it was 21.8% (P = 0.01). Infections were also more frequent in the ICU group (72.4% vs. 36.9% P < 0.001). The mortality rate among patients who needed ICU treatment was significantly higher when compared to the rest of the patients (53.6% vs. 7.8%; P < 0.001). CONCLUSIONS: In the Polish AAV cohort one in twenty patients required ICU admission. This group was characterized by multiple organ involvement and high mortality.