Safety of esthetic procedures in rheumatic patients: single-center survey of patients.

The popularity of esthetic medicine is growing every year, also among patients with autoimmune inflammatory rheumatic diseases (AIRD). The objective of this study was to evaluate the safety of esthetic medicine (AM) procedures in patients with AIRD. A semi-structured, anonymous questionnaire regarding rheumatic and concomitant diseases and AM procedures was distributed among adult patients hospitalized in the rheumatology department or attending outpatient clinic in the National Institute of Geriatrics, Rheumatology, and Rehabilitation, Warsaw. The main outcome was the occurrence of an adverse event. A number of 512 patients took part in the survey and 15 were excluded (AM procedure preceded the diagnosis of AIRD). The study group consisted of 497 patients, of whom 47 had undergone AM procedures. The procedures performed included: tattooing (22 patients), piercing (16 patients), hyaluronic acid (7 patients), botulinum toxin (5 patients) injections, laser procedures (6 patients), plastic surgery (4 patients), mesotherapy (3 patients) and others. The vast majority of patients had these performed during remission or low disease activity. 70.2% of patients received treatment with disease-modifying antirheumatic drugs (DMARDs) during the AM procedure, with TNF-alfa inhibitors being the most common (63.6%). Adverse events occurred in 15% of patients. All were mild and transient site reactions. Most patients would like to repeat the AM procedure in the future. The use of esthetic medicine procedures in patients with AIRD, including those treated with biologic DMARDs, was associated with a risk of mild site reactions. Most of the patients expressed satisfaction with the results of the AM procedure.

Predictors of treatment failure of non-steroidal anti-inflammatory drugs in patients with axial spondyloarthritis with focus on haptoglobin, haptoglobin polymorphism and zonulin.

According to the Assessment of SpondyloArthritis International Society-European Alliance of Associations for Rheumatology (ASAS-EULAR) recommendations for the management of axial spondyloarthritis (axSpA), patients should undergo at least two courses of non-steroidal anti-inflammatory drugs (NSAIDs) therapy. In our study, we enrolled axSpA patients both at onset and in a flare who had already been treated with NSAIDs ineffectively. Subsequently, according to the recommendations, they received modified NSAID treatment as another attempt to the first-line drug therapy and were monitored from there. We aimed to identify risk factors for treatment failure after 4 weeks (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score ≥ 4) especially amongst zonulin and haptoglobin concentrations, and haptoglobin polymorphism. Treatment failure was observed in 71% of patients, and the following variables were contributed for occurrence of this state: higher zonulin levels, ankylosing spondylitis, X-ray sacroiliitis, magnetic resonance imaging sacroiliitis, long duration of symptoms, high BASDAI, and high value of spinal pain intensity on visual analogue scale. In addition, the following positive correlations were found: haptoglobin concentration with C-reactive protein (r = 0.56; p = 0.0004), and erythrocyte sedimentation rate (r = 0.62; p < 0.0001), as well as between zonulin levels and white blood count (r = 0.5; p = 0.0003). The results of the study presented the identified factors related to the standard treatment failure in axSpA, amongst them zonulin levels. They might be applied to point out the patients for whom the search for a more appropriate method of treatment should be considered.

Do Not Leave Your Patients in the Dark-Using American College of Rheumatology and European Alliance of Associations for Rheumatology Recommendations for Vaccination in Polish Adult Patients with Autoimmune Inflammatory Rheumatic Diseases.

(1) Introduction: Patients with autoimmune inflammatory rheumatic diseases (AIIRD) face a higher infectious risk compared to the general population. As per the ACR and EULAR recommendations, vaccinations against influenza, COVID-19, pneumococci, and tetanus are recommended for most patients with AIIRD. (2) Objectives: This study aimed to assess vaccination coverage among Polish AIIRD patients and identify factors influencing it. (3) Patients and Methods: This study was conducted at the reference rheumatological center in Poland between May 2023 and October 2023. The study participants completed a questionnaire covering their knowledge of vaccination recommendations, actual vaccination status, factors affecting their decision to vaccinate, and their perspectives on immunization. (4) Results: This study involved 300 AIIRD patients and 60 controls. Both groups exhibited comparably low vaccination rates for all diseases (the highest for COVID-19-52% in both groups and the lowest for pneumococci-7.7% and 10%, respectively). Knowledge about recommended vaccinations was limited among patients in both groups. AIIRD patients were also not aware that they should avoid live vaccines. The primary motivators for vaccination among AIIRD patients were fear of infection (up to 75%) and medical advice (up to 74.6%). Conversely, the predominant reasons for non-vaccination were a lack of knowledge that vaccination is recommended (up to 74.7%) and concerns about potential adverse effects (up to 48.6%). Many patients reported not receiving vaccination recommendations from either primary care physicians or rheumatologists. (5) Conclusions: To enhance vaccination coverage among AIIRD patients in Poland, it is essential to educate them about vaccinations during routine medical consultations, emphasizing the increased risk of infection, informing them about recommended vaccinations, and clarifying doubts about adverse effects.

Mixed Connective Tissue Disease as Different Entity: Global Methylation Aspect.

Mixed connective tissue disease (MCTD) is a very rare disorder that belongs in the rare and clinically multifactorial groups of diseases. The pathogenesis of MCTD is still unclear. The best understood epigenetic alteration is DNA methylation whose role is to regulate gene expression. In the literature, there are ever-increasing assumptions that DNA methylation can be one of the possible reasons for the development of Autoimmune Connective Tissue Diseases (ACTDs) such as systemic sclerosis (SSc) and systemic lupus erythematosus (SLE). The aim of this study was to define the global DNA methylation changes between MCTD and other ACTDs patients in whole blood samples. The study included 54 MCTD patients, 43 SSc patients, 45 SLE patients, and 43 healthy donors (HC). The global DNA methylation level was measured by ELISA. Although the global DNA methylation was not significantly different between MCTD and control, we observed that hypomethylation distinguishes the MCTD patients from the SSc and SLE patients. The present analysis revealed a statistically significant difference of global methylation between SLE and MCTD (p < 0.001), SLE and HC (p = 0.008), SSc and MCTD (p ≤ 0.001), and SSc and HC (p < 0.001), but neither between MCTD and HC (p = 0.09) nor SSc and SLE (p = 0.08). The highest % of global methylation (median, IQR) has been observed in the group of patients with SLE [0.73 (0.43, 1.22] and SSc [0,91 (0.59, 1.50)], whereas in the MCTD [0.29 (0.20, 0.54)], patients and healthy subjects [0.51 (0.24, 0.70)] were comparable. In addition, our study provided evidence of different levels of global DNA methylation between the SSc subtypes (p = 0.01). Our study showed that patients with limited SSc had a significantly higher global methylation level when compared to diffuse SSc. Our data has shown that the level of global DNA methylation may not be a good diagnostic marker to distinguish MCTD from other ACTDs. Our research provides the groundwork for a more detailed examination of the significance of global DNA methylation as a distinguishing factor in patients with MCTD compared to other ACTDs patients.

Potential Mechanism of Fatigue Induction and Its Management by JAK Inhibitors in Inflammatory Rheumatic Diseases.

It is well known that fatigue is a highly disabling symptom commonly observed in inflammatory rheumatic diseases (IRDs). Fatigue is strongly associated with a poor quality of life and seems to be an independent predictor of job loss and disability in patients with different rheumatic diseases. Although the pathogenesis of fatigue remains unclear, indirect data suggest the cooperation of the immune system, the central and autonomic nervous system, and the neuroendocrine system in the induction and sustainment of fatigue in chronic diseases. Fatigue does not correspond with disease activity and its mechanism in IRDs. It is suggested that it may change over time and vary between individuals. Abnormal production of pro-inflammatory cytokines such as interleukin-6 (IL-6), interferons (IFNs), granulocyte-macrophage colony-stimulating factor (GM-CSF), TNF, IL-15, IL-17 play a role in both IRDs and subsequent fatigue development. Some of these cytokines such as IL-6, IFNs, GM-CSF, and common gamma-chain cytokines (IL-15, IL-2, and IL-7) activate the Janus Kinases (JAKs) family of intracellular tyrosine kinases. Therapy blocking JAKs (JAK inhibitors - JAKi) has been recently proven to be an effective approach for IRDs treatment, more efficient in pain reduction than anti-TNF. Therefore, the administration of JAKi to IRDs patients experiencing fatigue may find rational implications as a therapeutic modulator not only of disease inflammatory symptoms but also fatigue with its components like pain and neuropsychiatric features as well. In this review, we demonstrate the latest information on the mechanisms of fatigue in rheumatic diseases and the potential effect of JAKi on fatigue reduction.

Circulating miRNA-19b as a biomarker of disease progression and treatment response to baricitinib in rheumatoid arthritis patients through miRNA profiling of monocytes.

Introduction: A number of studies have demonstrated a key role of miRNA isolated from cells, tissue or body fluids as disease-specific biomarkers of autoimmune rheumatic diseases including rheumatoid arthritis (RA) and systemic sclerosis (SSc). Also, the expression level of miRNA is changing during disease development, therefore miRNA can be used as biomarkers monitoring RA progression and treatment response. In this study we have investigated the monocytes-specific miRNA that could serve as potential biomarkers of disease progression observed in sera and synovial fluids (SF) in early (eRA) and advanced (aRA) RA and in RA patients before and 3 months after selective JAK inhibitor (JAKi) -baricitinib treatment. Methods: Samples from healthy control (HC) (n=37), RA (n=44) and SSc (n=10) patients were used. MiRNA-seq of HC, RA, and SSc monocytes was performed to find versatile miRNA present in different rheumatic diseases. Selected miRNAs were validated in body fluids in eRA (<2 years disease onset) and aRA (>2 years disease onset) and RA patients receiving baricitinib. Results: Using miRNA-seq, we selected top 6 miRNA out of 95 that were significantly changed in both RA and SSc monocytes compared to HC. To identify circulating miRNA predicting RA progression, these 6 miRNA were measured in eRA and aRA sera and SF. Interestingly, miRNA (-19b-3p, -374a-5p, -3614-5p) were significantly increased in eRA sera vs HC and even further upregulated in SF vs aRA sera. In contrast, miRNA-29c-5p was significantly reduced in eRA sera vs HC and even further decreased in SF vs aRA sera. Kegg pathway analysis predicted that miRNA were involved in inflammatory-mediated pathways. ROC analysis demonstrated that miRNA-19b-3p (AUC=0.85, p=0.04) can be used as biomarker predicting JAKi response. Discussion: In conclusion, we identified and validated miRNA candidates which were present simultaneously in monocytes, sera, SF and that can be used as biomarkers predicting joint inflammation and monitoring therapy response to JAKi in RA patients.

Revising diagnosis of juvenile idiopathic arthritis in adults: a single-center retrospective study.

The study aimed to assess how many adult patients with juvenile idiopathic arthritis (JIA) treated with biologics fulfill classification criteria for adult rheumatic diseases and to evaluate the course of JIA in adulthood. 138 patients with JIA over 18 years old treated with biologics were included in a cross-sectional observative study. Among 138 adult patients with JIA treated with biologics, 81 patients remained with JIA diagnosis. 57 patients were rediagnosed. 31 patients met the criteria for spondyloarthropathy, among them 18 patients for ankylosing spondylitis, 10 patients for psoriatic arthritis, and 3 patients for non-radiographic axial spondyloarthritis. Rheumatoid arthritis was diagnosed in 24 patients and adults' Still disease in 2 patients. 84 patients of all adults with JIA received one biologic agent, 40 received two biologic agents, and 14 received three or more biologic therapies. 10 patients received biologic agents out of recommendations for JIA. Of the adult JIA patients treated with biologics, 41% met the classification criteria for adult inflammatory diseases. Spondyloarthropathy and rheumatoid arthritis were most commonly diagnosed. Nearly 40% of adult JIA patients required at least one modification of biological treatment. Therefore, it is worth considering a revision of JIA to adult-onset inflammatory disease entities, as it broadens the spectrum of disease-modifying drugs.

The Kinetics of Humoral and Cellular Responses after the Booster Dose of COVID-19 Vaccine in Inflammatory Arthritis Patients.

Impaired immunogenicity of COVID-19 vaccinations in inflammatory arthritis (IA) patients results in diminished immunity. However, optimal booster vaccination regimens are still unknown. Therefore, this study aimed to assess the kinetics of humoral and cellular responses in IA patients after the COVID-19 booster. In 29 IA patients and 16 healthy controls (HC), humoral responses (level of IgG antibodies) and cellular responses (IFN-γ production) were assessed before (T0), after 4 weeks (T1), and after more than 6 months (T2) from the booster vaccination with BNT162b2. IA patients, but not HC, showed lower anti-S-IgG concentration and IGRA fold change at T2 compared to T1 (p = 0.026 and p = 0.031). Furthermore, in IA patients the level of cellular response at T2 returned to the pre-booster level (T0). All immunomodulatory drugs, except IL-6 and IL-17 inhibitors for the humoral and IL-17 inhibitors for the cellular response, impaired the immunogenicity of the booster dose at T2. Our study showed impaired kinetics of both humoral and cellular responses after the booster dose of the COVID-19 vaccine in IA patients, which, in the case of cellular response, did not allow the vaccination effect to be maintained for more than 6 months. Repetitive vaccination with subsequent booster doses seems to be necessary for IA patients.

Multicenter evaluation of tofacitinib retention and safety in rheumatoid arthritis - why cardiovascular risk factors do not equate to overt risk.

Introduction: This multicenter, real-world, retrospective cohort study aimed to assess the effectiveness and safety of tofacitinib (TOFA) in rheumatoid arthritis (RA). Material and methods: Two hundred nine patients with active RA treated with TOFA, unresponsive to at least 2 conventional synthetic disease-modifying drugs, were recruited. Clinical characteristics were extracted from an electronic registry and supplemented with manual chart review and data linkage with ambulatory care. Drug retention and reasons for discontinuation were evaluated. Results: Median (interquartile range) follow-up in the whole sample was 16.9 (5.93-31.7) months. Mean (standard deviation) age was 51.44 (±11.84) years, with female predominance (n = 168, 80.4%). Only 30 patients (14.4%) had no pre-existing traditional cardiovascular (CV) risk factor at TOFA initiation. Tofacitinib retention rates were high, with median survival estimated at 89.3% at 6 months, 82.4% at 12 months, and 60.4% at 24 months. Ineffectiveness was the primary cause of discontinuation (n = 50). The rate of adverse events (AEs) was relatively low, with lipid abnormalities, blood count alterations, and infectious events among the most common. No major adverse CV event was reported. The incidence rate of AEs necessitating treatment switch was 60.34 (95% CI: 37-92) per 1,000 person-years of follow-up. Presence of multiple (> 3) CV risk factors was associated with lower odds of TOFA retention and treatment effectiveness. Conclusions: Tofacitinib demonstrated high retention rates and a favorable safety profile in RA patients, including those with traditional CV risk factors. Tofacitinib may be a valuable treatment option for RA patients when combined with individualized CV risk management. Further studies are warranted to explore the long-term effects of TOFA and its CV impact in larger populations.

Humoral and cellular immunogenicity of COVID-19 booster dose vaccination in inflammatory arthritis patients.

Introduction: Previous studies have shown a reduction in the effectiveness of primary COVID-19 vaccination in patients with rheumatic diseases. However, limited data is available regarding the effectiveness of the COVID-19 vaccine booster dose, especially on cellular response. The study aimed to assess the humoral and cellular immunogenicity of a booster dose in patients with inflammatory arthritis (IA). Patients and methods: 49 IA and 47 age and sex-matched healthy controls (HC) were included in a prospective cohort study. Both groups completed primary COVID-19 vaccination and after more than 180 days received a BNT162b2 booster shot. Humoral responses (level of IgG antibodies) and cellular responses (IFN-γ production) were assessed before and after 4 weeks from the booster dose of the vaccine. Results: After the booster dose, all participants showed an increased humoral response, although significantly reduced antibody levels were observed in IA patients compared to HC (p=0.004). The cellular response was significantly lower both before (p<0.001) and after (p<0.001) the booster dose in IA patients as compared to HC. Among the immunomodulatory drugs, only biological and targeted synthetic drugs lowered the humoral response after booster vaccination. However, the cellular response was decreased after all immunomodulatory drugs except IL-17 inhibitors and sulfasalazine. Conclusion: Our data indicate that patients with rheumatic diseases present lower humoral and cellular responses after the COVID-19 booster vaccine in comparison to HC. This may translate into a recommendation for subsequent booster doses of the COVID-19 vaccine for rheumatic patients.

Coronavirus disease 2019 vaccination uptake and hesitancy among Polish patients with inborn errors of immunity, autoinflammatory syndromes, and rheumatic diseases: A multicenter survey.

Data regarding the willingness of patients affected by inborn errors of immunity to accept vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited. Therefore, this study assessed SARS-CoV-2 vaccination coverage and hesitancy in immunodeficient patients by surveying adults with primary immune deficiencies and autoinflammatory and rheumatic diseases on biologic therapy. The study was conducted from September 20, 2021, to January 22, 2022, when the primary coronavirus disease 2019 (COVID-19) vaccinations were available to all adults in Poland. We included 207 participants consecutively recruited from five referral centers (57% female; median age: 42.6 [range: 18-76, standard deviation ± 14.70] years). Overall, 55% (n = 114), 17% (n = 36), and 28% (n = 57) of the patients had primary immune deficiencies, autoinflammatory diseases, and rheumatic diseases, respectively. Among the entire cohort, 168 patients (81%) were vaccinated, and 82% were willing to receive a booster dose. Patients with autoinflammatory diseases had the highest vaccination rate (94.4%). A strong conviction that it was the correct decision (72%), fear of getting COVID-19 (38%), and expert opinions (34%) influenced the decision to vaccinate. Among the unvaccinated patients, 33.3% had primary or vocational education (p <0.001). Furthermore, only 33% believed they were at risk of a severe course of COVID-19 (p = 0.014), and 10% believed in vaccine efficacy (p <0.001). They also doubted the safety of the vaccine (p <0.001) and feared a post-vaccination flare of their disease (p <0.001). Half of the unvaccinated respondents declared that they would consider changing their decision. Vaccination coverage in immunodeficient patients was higher than in the general Polish population. However, the hesitant patients doubted the vaccine's safety, feared a post-vaccination disease flare, and had primary or vocational education. Therefore, vaccination promotion activities should stress personal safety and the low risk of disease flares due to vaccination. Furthermore, all evidence must be communicated in patient-friendly terms.

IL-1ß, IL-10 and TNF-α polymorphisms may affect systemic lupus erythematosus risk and phenotype.

OBJECTIVES: Systemic lupus erythematosus (SLE) is an autoimmune disease, and IL-1ß, IL-10, and TNF-α genes are important in the pathogenesis of this disease. We studied the impact of IL-1ß-511, IL-1ß +3953, IL-10 -592, IL-10 -1082, TNF-α -308, TNF-α -238, and TNF-α +489 polymorphisms on SLE risk and phenotype in SLE patients and healthy controls. METHODS: We genotyped SLE patients and healthy controls by real-time PCR on QuantStudio 5 (Applied Biosystems) and measured levels of cytokines by enzyme-linked immunosorbent assay (ELISA). RESULTS: We indicated that TNF-α -308, IL-10 -592, IL-10 -1082, IL-1ß-511 and IL-1ß +3953 polymorphisms affect SLE risk. Furthermore, we exposed that some of the TNF-α +489, TNF-α -238, IL-10 -1082 and IL-1ß +3953 genotypes are connected with the SLE phenotype. Moreover, we discovered the linking between specific genotypes and the serum concentrations of TNF-α, IL-1ß, and IL-10. CONCLUSIONS: In conclusion, our study revealed that IL-1ß-511, IL-1ß +3953, IL-10 -592, IL-10 -1082, and TNF-α -308 polymorphisms may affect SLE risk and phenotype.

Relationship between type of skin lesions and nailfold capillaroscopy pattern in mixed connective tissue disease.

INTRODUCTION: Mixed connective tissue disease (MCTD) is a rare disease with clinical picture consisted of multiple organ manifestations, including skin changes resembling systemic lupus erythematosus (SLE), systemic sclerosis (SSc), or dermatomyositis (DM). On the background of these manifestations are microvascular changes - alteration of endothelial function and impairment of endothelial progenitor cell. Nailfold capillaroscopy (NFC) is a simple, non-invasive technique for investigating microvascular involvement in rheumatic diseases. OBJECTIVES: To describe the relationship between type of skin lesions and NFC pattern in MCTD patients. METHODS: We analyzed the clinical picture and NFC patterns in 79 patients with MCTD. The NFC changes were classified into Normal, "Early," "Active," and "Late" scleroderma-like patterns (SD-like pattern) based on Cutolo classification. In all patients, subjective and physical examinations were carried out, specifically the occurrence of skin lesions in the course of MCTD was assessed (systemic sclerosis-like (Ssc-like), systemic lupus erythematosus-like (SLE-like), dermatomysitis-like (DM-like)). RESULTS: Skin changes were present in 64 (81%) patients, involving 43 (54%) SLE-like, 48 (61%) SSc-like, and 4 (5.1%) DM-like. NFC changes were observed in a total of 55 (69.6 %) patients with predominance of the "Early" pattern - 41 (51.9 %) patients. According to skin change phenotypes, NFC changes were observed in 31 (72%) patients with SLE-like and in 32 (66.7%) patients with SSc-like skin phenotypes. The "early" pattern predominated in both group. CONCLUSIONS: We did not find any correlation between NFC pattern and the type skin changes. Key Points • The study did not show a correlation between the presence and absence of skin lesions and NFC pattern. • Scleroderma-like patterns were found in over 60% of patients with mixed connective tissue disease. • The "early" pattern is dominant regardless of the occurrence or absence of skin lesions in patients with MCTD. • Skin lesions, regardless of their type (SLE or SSc), do not correlate with type of lesion found in the NFC examination.

Is intra-articular infliximab therapy a good alternative to radionuclide synovectomy for a patient with refractory pigmented villonodular synovitis?

Pigmented villonodular synovitis (PVNS) is a rare disease that has clinical and histopathological characteristics of both benign proliferative disorder and a chronic inflammatory process of the synovial tissue. The primary mode of treatment is surgery followed by an adjuvant radiotherapy; however, the risk of recurrence is a significant (40-70%). Several publications suggest that the TNF-α inhibitors might be a treatment option. We present a case of a 29-year-old female diagnosed with PVNS of the knee joint, refractory to surgery and 3 radionuclide synovectomies. Because the possibilities of conventional therapy were exhausted, treatment with an intra-articular anti-TNF-α monoclonal antibody (infliximab) was performed. Despite a high safety profile and a good tolerance of that therapy we did not observe significant clinical and radiological improvement. To assess the effectiveness of intra-articular TNF-α inhibitors as an adjuvant treatment in PVNS, prospective studies are needed.

Microvascular damage - a marker of specific organ involvement in mixed connective tissue disease?

Mixed connective tissue disease (MCTD) is a complex entity, which incorporates features of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc) and polymyositis/dermatomyositis (PM/DM). Nailfold videocapillaroscopy (NVC) is a simple, safe and non-invasive technique of capillary vessel assessment, allowing for qualitative and quantitative assessment of microcirculation. NVC plays a pivotal role in the diagnostic algorithm of connective tissue diseases, especially in systemic sclerosis (SSc). Numerous studies have shown a correlation between organ involvement and disease progression in SSc. In the current literature, there are limited data on relationship between NVC and organ involvement in MCTD patients. In the present article the relevant literature describing NVC examination in patients with MCTD and comparisons with some clinical situations are discussed.

The Role of TNF-α and Anti-TNF-α Agents during Preconception, Pregnancy, and Breastfeeding.

Tumor necrosis factor-alpha (TNF-α) is a multifunctional Th1 cytokine and one of the most important inflammatory cytokines. In pregnancy, TNF-α influences hormone synthesis, placental architecture, and embryonic development. It was also shown that increased levels of TNF-α are associated with pregnancy loss and preeclampsia. Increased TNF-α levels in complicated pregnancy draw attention to trophoblast biology, especially migratory activity, syncytialisation, and endocrine function. Additionally, elevated TNF-α levels may affect the maternal-fetal relationship by altering the secretory profile of placental immunomodulatory factors, which in turn affects maternal immune cells. There is growing evidence that metabolic/pro-inflammatory cytokines can program early placental functions and growth in the first trimester of pregnancy. Furthermore, early pregnancy placenta has a direct impact on fetal development and maternal immune system diseases that release inflammatory (e.g., TNF-α) and immunomodulatory factors, such as chronic inflammatory rheumatic, gastroenterological, or dermatological diseases, and may result in an abnormal release of cytokines and chemokines in syncytiotrophoblasts. Pregnancy poses a challenge in the treatment of chronic disease in patients who plan to have children. The activity of the disease, the impact of pregnancy on the course of the disease, and the safety of pharmacotherapy, including anti-rheumatic agents, in pregnancy should be considered.

Association study between immune-related miRNAs and mixed connective tissue disease.

BACKGROUND: Mixed connective tissue disease (MCTD) is a rare condition that is distinguished by the presence of specific U1-RNP antibodies. Information about its etiopathology and diagnostics is still unclear. miRNAs such as miR-146, miR-155, and miR-143 emerged as key regulators of the immune system, known to be involved in the development of autoimmune diseases and cancers. We performed an association study between immune-related miRNAs and MCTD severity and susceptibility. METHODS: A total of 169 MCTD patients and 575 healthy subjects were recruited to the case-control study. The miRNA polymorphisms were genotyped using TaqMan SNP genotyping assay. TNF-α, IL-6, and IFN-γ levels in serum were determined using ELISA. qRT-PCR of TRAF6, IRAK1, and microRNAs was performed using Taqman miRNA assays and TaqMan Gene Expression Assays. RESULTS: miR-146a rs2910164 G allele and GG genotype as well as miR-143 rs713147 A allele were more frequent in healthy subjects than in MCTD patients. miR-146a rs2910164 CC genotype and miR-143 T-rs353299*T-rs353291*T-rs713147*G-rs353298 and C-rs353299*C-rs353291*T-rs713147*A-rs353298 haplotypes were associated with MCTD susceptibility. miR-146a rs2910164 C/T was associated with scleroderma and lymphadenopathy. miR-143 rs353299 C/T was associated with swollen fingers or hands, the presence of enlarged lymph nodes, and pericarditis/pleuritis. miR-143 rs353298 A/G was associated with the occurrence of pericarditis/pleuritis and scleroderma. miR-143 rs353291 T/C showed association with pericarditis/pleuritis. The serum TNF-α, IFN-γ, and IL-6 levels were significantly higher in MCTD patients compared to healthy subjects. miR-143 SNPs were associated with higher proinflammatory cytokine concentration in serum only in healthy controls. IRAK1 and TRAF6 expression were higher in the MCTD patients compared to controls. CONCLUSIONS: The results of our case-control study indicate the possible significance of miR-146a and miR-143/145 in the susceptibility and clinical picture of MCTD.

Schnitzler Syndrome in a 27-Year-Old Man: Diagnostic and Therapeutic Dilemma in Adult Auto-Inflammatory Syndromes A Case Report and Literature Review.

A 32-year-old-man, with a history of chronic urticaria from the age of 27, diagnosed with an adult-onset Still's disease and received a low dose of glucocorticoids, methotrexate and tocilizumab. Despite the long-term combined treatments, he suffered from chronic urticaria, low-grade fever and bone pain. He was found to have high inflammatory markers, hypogammaglobulinemia, monoclonal IgM - kappa light chain in serum and increased radiotracer uptake in the whole bone scintigraphy. No pathological variants for monogenic autoinflammatory diseases were present in the genome exome sequencing. These investigations confirmed the diagnosis of Schnitzler syndrome, which is an exception before the age of 35. Switching from tocilizumab to interleukin 1 receptor inhibitor, anakinra led to a full clinical response and normalisation of inflammatory markers. Patients with a history of fever and chronic urticaria are routinely tested for monoclonal gammopathy in the context of malignancy, but it should also be considered as a sign of the autoinflammatory syndrome. The Schnitzler syndrome and the adult-onset Still's disease share common features, so the diagnosis requires a thorough investigation to establish an optimal treatment. In the diagnostic algorithm, monoclonal gammopathy is usually considered red flag for malignancy but might be overlooked as a criterion of Schnitzler syndrome, particularly in young adults. We confirm that the interleukin 1 inhibitor should be the first line of therapy in Schnitzler syndrome, and in the presented case we found it more effective than the interleukin 6 blockade. The main goal of this paper is to increase awareness of Schnitzler syndrome among health care professionals. We aim to present features which can be helpful in differential diagnosis.

The Role of MECP2 and CCR5 Polymorphisms on the Development and Course of Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic and systemic autoimmune disease. SLE is described by production of autoantibodies and causes damage of many organs. T-cells play a crucial role in SLE pathogenesis. T-cells intensify inflammation through a number of processes, which leads to autoimmunization. CCR5 and MECP2 genes are linked with T-cells and pathogenesis of SLE. Polymorphisms in these genes are related with the prognostic factors of risk of disease onset and disease severity. The aim of this study was to estimate the influence of polymorphisms in MECP2 and CCR5 genes on the development and course of systemic lupus erythematosus. We examined 137 SLE patients and 604 healthy controls. We studied polymorphisms for CCR5 gene: rs333 and for MECP2: rs2075596, rs1734787, rs17435, and rs2239464. We genotyped our MECP2 samples and we performed a restriction fragment length polymorphism (RFLP) analysis for CCR5 samples. We showed a risk factor for allele T in rs17435 and for allele A in rs2075596 in MECP2. We noticed that MECP2 rs2075596 G/A, rs1734787 C/A, rs17435 A/T, and rs2239464 G/A polymorphisms are more prevalent in SLE patients than in healthy controls. We believe that above-mentioned MECP2 polymorphisms can be considered as SLE susceptibility factor.