The problem of residual pain in the assessment of rheumatoid arthritis activity.

Residual pain is a major unmet medical need observed in patients suffering from rheumatoid arthritis (RA), which decreases their quality of life, even after achieving remission or low disease activity. The article has two aims: 1) to present mechanisms involved in the pathophysiology of residual pain, both inflammatory and non-inflammatory, i.e. neuropathic and nociplastic pain, as well as secondary pain syndromes, i.e. osteoarthritis and fibromyalgia, which can contribute to residual pain; 2) to show the limitations of current disease activity measures recommended by European Alliance of Associations for Rheumatology (EULAR) and American College of Rheumatology (ACR), which raise the need for a separate assessment of pain, and examples of methods that could be used by medical professionals to assess the pain and make a differential diagnosis. In conclusion, establishing a valid method to assess pain is essential to identify the pathomechanism of residual pain and to create treatments tailored specifically to individual RA patients.

COVID-19 prophylaxis, diagnostics, and treatment in patients with rheumatic diseases. The Polish experts panel opinion.

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolves, infection management in vulnerable populations requires formalized guidance. Although low-virulence variants of SARS-CoV-2 remain predominant, they pose an increased risk of severe illness in adults with rheumatic and musculoskeletal diseases (RMDs). Several disease-specific (chronic long-grade inflammation, concomitant immunosuppression) and individual (advanced age, multimorbidity, pregnancy, vaccination status) factors contribute to excess risk in RMD populations. Various post-COVID-19 manifestations are also increasingly reported and appear more commonly than in the general population. At a pathogenetic level, complex interplay involving innate and acquired immune dysregulation, viral persistence, and genetic predisposition shapes a unique susceptibility profile. Moreover, incident cases of SARS-CoV-2 infection as a trigger factor for the development of autoimmune conditions have been reported. Vaccination remains a key preventive strategy, and encouraging active education and awareness will be crucial for rheumatologists in the upcoming years. In patients with RMDs, COVID-19 vaccines' benefits outweigh the risks. Derivation of specialized diagnostic and therapeutic protocols within a comprehensive COVID-19 care plan represents an ideal scenario for healthcare system organization. Vigilance for symptoms of infection and rapid diagnosis are key for introducing antiviral treatment in patients with RMDs in a timely manner. This review provides updated guidance on optimal immunization, diagnosis, and antiviral treatment strategies.

Liquid Biopsy and Its Emerging Role in Rheumatology.

Liquid biopsy is a rapidly evolving diagnostic technique used to analyze tissue-derived information found in the blood or other bodily fluids. It represents a new way to guide therapeutic decisions, mainly in cancer, but its application in other fields of medicine is still growing. Here, we discuss how liquid biopsy has been used in autoimmune rheumatic diseases such as rheumatoid arthritis, systemic lupus erythematosus, or primary Sjögren's syndrome. Additionally, in aspect of liquid biopsy, we analyze the molecular biomarkers utilized in the field of rheumatology, including circulating cell-free DNA, microRNA, and proteomic content.

The Role of the Microbiome in Sjogren's Syndrome.

The human microbiome is a living ecosystem existing within the host organism, determined by a balance between pathogenic microorganisms, symbionts, and commensals. The disturbance of microbiome composition-dysbiosis-often resulting in the excess of commensal numbers, may push the immune system towards activation of inflammatory and autoimmune processes. Changes in the microbiome of gut, eyes, and mouth may play a significant role in the development and course of autoimmune diseases, including primary Sjogren's syndrome. This autoimmune disease is associated with changes in the protective barrier of the epithelium, which is an important part of the antimicrobial defense. The development of pSS may be influenced by a mechanism of molecular mimicry between microbial antigens and self antigens leading to the initiation of anti-Ro60 antibody response. The knowledge of the influence of the state of microbiome on pSS may translate into the prophylaxis of the progression of dryness symptoms. The aim of this review is to present various aspects related to the human microbiome and Sjogren's syndrome.

Omega-3 fatty acids in the treatment of spinal cord injury: untapped potential for therapeutic intervention?

Omega-3 fatty acids constitute a group of fatty acids with anti-inflammatory and preventive effects against various diseases. Studies in animal models have demonstrated the preventive and therapeutic effects of omega-3 fatty acids after spinal cord injury (SCI) in reducing inflammatory reactions and promoting neuroregeneration. However, studies on the efficacy of omega-3 fatty acids in treatment and prevention after SCI seem to be questionable. This study evaluates potential reasons for omega-3 fatty acid therapy oversight in populations after SCI. Therefore, some of the reasons could cover heterogeneous patient groups in size, level of injury, quality of life assessment, time since injury, no single standardised dose, various follow-up durations and metabolic changes, often insufficient to record. Due to the difficulty of collecting cases for the study, especially in the acute phase after SCI, multicenter, coordinated studies are needed to establish the effects of omega-3 fatty acids on treatment, recovery, and disease prevention in patients after SCI. Although the present results of such studies are still inconclusive, the failure to exploit the potential properties of omega-3 fatty acids in the treatment of patients with SCI solely due to methodological difficulties should be considered a potential waste.

Shear wave elastography as a potential additional diagnostic tool in primary Sjögren's syndrome: an observational study.

The primary aim of this study was to verify if shear wave elastography can be used to evaluate salivary gland involvement in primary Sjögren's syndrome (pSS). The secondary objective was to establish an accurate cut-off value for parotid and submandibular salivary gland stiffness and to verify whether there are any distinctions among pSS patients with or without subjective mouth dryness. This prospective study included 45 patients with pSS (2016 ACR/EULAR classification criteria) and 108 healthy controls. All subjects underwent bilateral shear wave elastography of the parotid and submandibular salivary glands. Clinical data of pSS patients were collected and compared to elastography results. Patients with pSS had significantly higher shear wave elastography values for the parotid and submandibular salivary glands than the controls. There were no statistical differences in SWE values between patients with or without mouth dryness. The optimal cut-off value (mean value of 4 salivary glands shear wave elastography results) to distinguish patients with or without pSS was 13.19 kPa with sensitivity = 97.8% and specificity = 100.0%. It was, therefore, confirmed that shear wave elastography measurement of salivary glands has strong predictive ability in pSS detection (AUC 97.8%, 95% CI 93.4-100.0%). Shear wave elastography seems to be a promising, non-invasive and simple quantitative adjunct test to support the diagnosis of pSS with good sensitivity and specificity. More extensive prospective studies are needed to standardize a study protocol.

Prevention and risk assessment of cardiovascular events in a population of patients with psoriasis and psoriatic arthritis.

Psoriasis is a chronic, inflammatory, often relapsing disease that is frequently associated with other diseases of similar pathogenesis. The multi-morbidity in the psoriasis population significantly impedes both diagnosis and implementation of appropriate preventive measures. However, the common denominator for this group of diseases is the inflammatory process that initiates the appearance of subsequent symptoms and health consequences, most of which can be avoided or alleviated by modifying the patient's lifestyle and incorporating appropriate treatment. Health consequences associated with systemic inflammation include cardiovascular incidents and other cardiometabolic diseases. This article was based on available publications on the onset, incidence, and prevention of cardiovascular disease in the psoriasis patient population.

IgA immunoglobulin isotype of rheumatoid factor in primary Sjögren's syndrome.

Primary Sjögren's syndrome (pSS) is an autoimmune disease with autoantibodies overproduction, including rheumatoid factors (RF). RF-IgA, IgG immunoglobulin classes are suggested as potential biomarkers of pSS. We studied 76 patients with pSS (ACR/Eular 2017); laboratory tests included ESR, C-reactive protein, concentrations of gamma globulins, RF, Anti-SS-A/Ro, and anti-SS-B/La. Eye dryness and keratoconjunctivitis sicca were confirmed with Schirmer's test, the ocular staining score (OSS) using lissamine green, fluorescein staining and biopsy of minor salivary gland with the histopathological evaluation. Differences between groups were analyzed with U Mann-Whitney test. Correlations between quantitative variables were assessed with the Spearman correlation coefficient.. The best diagnostic values of immunoglobulin concentration for discriminating pSS patients and healthy individuals are for RF-IgA. With cut-off of 21.5 EU/mL, the sensitivity is 72% and specificity is 100%. Very high specificity (100%) is also obtained for RF-IgM concentration of 74.1 EU/mL. Sensitivity is, however, smaller than that for RF-IgA and amounted to 61%. The RF-IgG is the poorest indicator of pSS with 51% of sensitivity and 95% of specificity. To summarize RF-IgA strongly associate with anti-SS-A and anti-SS-B autoantibodies. Both RF-IgA and RF-IgM may be used as diagnostic tools for pSS. Conclusions: among the three studied rheumatoid factor subtypes, RF-IgA showed the best diagnostic accuracy for pSS. RF-IgA correlated with anti-SS-A/Ro and anti-SS-B antibodies even more closely than RF-IgM. The assessment of the RF-IgA serum concentration may be helpful in the process of establishing pSS diagnosis.

High-resolution ultrasound imaging of skin involvement in systemic sclerosis: a systematic review.

To collect evidence on the application of ultrasound in skin assessment in patients with systemic sclerosis (SSc). The authors carried out a review of the literature via Pubmed MEDLINE database. The search terms were: skin imaging in systemic sclerosis, ultrasound skin imaging in patients with systemic sclerosis. The selection and analysis of articles were performed by two independent evaluators. The authors analyzed 10 studies characterizing 470 patients with systemic sclerosis. The patients were young adults, mainly women. The described methods of ultrasound were: ultrasound elastography (7.14%), ultra-high-frequency (7.14%) and B-mode ultrasonographic imaging (21.43%), high-frequency ultrasonography (21.43%), shear-wave elastography (21.43%) and others (21.43%). Skin measurements reported in the analyzed studies were: skin ultrasound in all studies, skin thickness (8 studies), skin elasticity (5 studies), skin stiffness (2 studies), subcutaneous tissue thickness (1 study). Ultrasound measurements were compared to different types of scales and measurements used in the description of disease progression. Ultrasound may be used in the clinical assessment of skin involvement in SSc. To the best of our knowledge, articles currently reporting the use of ultrasound in skin imaging show interesting ideas and provide basis for further research. Skin involvement in SSc assessed with ultrasound should be compared to skin biopsy. It is necessary to develop guidance for conducting skin measurements using ultrasound in patients with scleroderma. Currently, skin imaging in SSc is of limited clinical use due to a variety of methods and the lack of a standard operating procedure. The authors of analyzed studies suggested that high-frequency ultrasound provided a quantitative and reliable evaluation of dermal thickness in patients with SSc.

Copper, Iron, and Manganese Toxicity in Neuropsychiatric Conditions.

Copper, manganese, and iron are vital elements required for the appropriate development and the general preservation of good health. Additionally, these essential metals play key roles in ensuring proper brain development and function. They also play vital roles in the central nervous system as significant cofactors for several enzymes, including the antioxidant enzyme superoxide dismutase (SOD) and other enzymes that take part in the creation and breakdown of neurotransmitters in the brain. An imbalance in the levels of these metals weakens the structural, regulatory, and catalytic roles of different enzymes, proteins, receptors, and transporters and is known to provoke the development of various neurological conditions through different mechanisms, such as via induction of oxidative stress, increased α-synuclein aggregation and fibril formation, and stimulation of microglial cells, thus resulting in inflammation and reduced production of metalloproteins. In the present review, the authors focus on neurological disorders with psychiatric signs associated with copper, iron, and manganese excess and the diagnosis and potential treatment of such disorders. In our review, we described diseases related to these metals, such as aceruloplasminaemia, neuroferritinopathy, pantothenate kinase-associated neurodegeneration (PKAN) and other very rare classical NBIA forms, manganism, attention-deficit/hyperactivity disorder (ADHD), ephedrone encephalopathy, HMNDYT1-SLC30A10 deficiency (HMNDYT1), HMNDYT2-SLC39A14 deficiency, CDG2N-SLC39A8 deficiency, hepatic encephalopathy, prion disease and "prion-like disease", amyotrophic lateral sclerosis, Huntington's disease, Friedreich's ataxia, and depression.

Antimitochondrial Antibodies and Primary Biliary Cholangitis in Patients with Polymyalgia Rheumatica/Giant Cell Arteritis.

Background and Objectives: Laboratory liver abnormalities can be observed in patients affected with polymyalgia rheumatica (PMR) and/or giant cell arteritis (GCA), especially with a cholestatic pattern. The first objective of our review article is to discuss the potential link between antimitochondrial antibodies (AMA) and/or primary biliary cholangitis (PBC) and PMR/GCA, according to the evidences of literature. The second objective is to discuss the association of PMR/GCA with the other rheumatic diseases having PBC as a common manifestation. Materials and Methods: A literature search was performed on PubMed and Medline (OVID interface) using these terms: polymyalgia rheumatica, giant cell arteritis, antimitochondrial antibodies, primary biliary cholangitis, primary Sjogren's syndrome, systemic sclerosis, and systemic lupus erythematosus. The search was restricted to all studies and case reports published in any language. Reviews, conference abstracts, comments, and non-original articles were excluded; however, each review's reference list was scanned for additional publications meeting this study's aim. When papers reported data partially presented in previous articles, we referred to the most recent published data. Results and Conclusions: Our literature search highlighted that cases reporting an association between AMA, PBC and PMR/GCA were very uncommon; AMA antigenic specificity had never been detected and biopsy-proven PBC was reported only in one patient with PMR/GCA. Finally, the association of PMR/GCA with autoimmune rheumatic diseases in which PBC is relatively common was anecdotal.

Dysbiosis, gut-blood barrier rupture and autoimmune response in rheumatoid arthritis and schizophrenia.

The primary cause of chronic autoimmune diseases is elusive both in somatic medicine and psychiatry. Examples of such conditions are rheumatoid arthritis and schizophrenic disorders. Immune disturbances occur in both diseases, but it is difficult to combine them into a meaningful pathogenetic model. The immunological hypothesis of schizophrenia is based on non-specific changes in the cytokine system and exponents of chronic inflammation in some patients. In rheumatoid arthritis the cytokine network is much better known than in schizophrenia, and interleukin-6, tumor necrosis factor or Janus kinases became a target of treatment. Microbiome dysbiosis and disturbances of the blood-gut barrier may be a new hypothesis of the pathogenesis of somatic and psychiatric diseases. The purpose of this narrative review was to show, using the example of two chronic diseases - rheumatoid arthritis and schizophrenic disorders - that disturbances in the blood barrier of the intestine can be a common mechanism of somatic and mental disorders. The paper presents the current state of knowledge on the hypothetical relationship between microbiome dysbiosis and the pathogenesis of schizophrenia and rheumatoid arthritis. In conclusion, in the light of discoveries regarding the microbiome-gut-brain axis the immunological model of rheumatoid arthritis and schizophrenia formation may gain importance and contribute to the creation of new strategies for causal treatment of these still incurable diseases.

How to perform high ultrasound examination of skin involvement among patients with systemic sclerosis - proposition of a unified protocol.

INTRODUCTION: A fast and cheap method of skin assessment in systemic sclerosis (SSc) is an area of extensive research. Established in 1979, the Rodnan skin score is a palpation-based method used among clinicians. This method has some limitations, such as: examiner's skills, subjective results, and no standardization. In the last few years researchers have been exploring ultrasound-based techniques as a possible tool for skin assessment among patients with SSc. The aim of the study is to develop a protocol of elastography-based skin imaging evaluation among patients with SSc. MATERIAL AND METHODS: Review of the literature and own experience. RESULTS: Proposition of elastography-based skin imaging protocol among patients with SSc. CONCLUSIONS: The authors present a potential protocol of ultrasound-based examination of skin involvement among patients with SSc.

Autoimmune syndrome induced by adjuvants after breast enhancement with polyacrylamide hydrogel: a study in Poland.

Autoimmune syndrome induced by adjuvants (ASIA) is the spectrum of diseases in which the substances considered inert to the body induce autoimmune reactions and inflammation. Some of the biomaterials recently used in plastic surgery, such as silicone or polyacrylamide hydrogel (PAAG) seem to trigger clinical features of ASIA. The aim of this study was to assess the incidence of these features within a group of women after breast augmentation with PAAG. As many as 30 consecutive patients (26-59 years, mean age 39.5) referred to the Clinic of Plastic Surgery after breast enhancement with PAAG were examined. The validated criteria of ASIA syndrome were employed. Descriptive statistics were chosen based on the distribution of variables. The research was approved by the Bioethical Committee of the Centre of Postgraduate Medical Education in Warsaw, Poland. Within the studied group, 50% of patients (n = 15) fulfilled ASIA diagnostic criteria. Apart from local complications, we encountered various general symptoms, among which fever (n = 13, 43.3%), tingling and numbness of upper extremities (n = 10, 33.3%) and chronic fatigue (n = 9, 30%) were the most common. These symptoms were present on an ambulatory visit, before qualification to the operation of hydrogel removal. All patients undergoing surgical PAAG removal (n = 8) declared alleviation or complete resolution of the symptoms. Polyacrylamide hydrogel breast filling, although limiting the invasiveness of the procedure in relation to silicone breast implants, also carries the risk of developing ASIA symptoms. The removal of PAAG may bring improvement in some cases.

Applicability of shear wave elastography for the evaluation of skin strain in systemic sclerosis.

The assessment of skin fibrosis is vital for the diagnosis and monitoring of treatment in the systemic sclerosis (SSc)-a severe autoimmune disease. The elastography is a technique of skin fibrosis assessment through the evaluation of skin strain. We compared the efficacy of the shear wave elastography (SWE) and commonly used modified Rodnan skin score (RSS) in skin fibrosis assessment in SSc. The study included 40 SSc patients and 28 healthy individuals, with the exclusion of individuals with other skin/autoimmune diseases. Skin thickness using RSS and skin strain using SWE were assessed in the same 20 body localizations. Subjects' informed consent and the bioethics committee approval were obtained. Elastographic skin strain correlated positively with both partial and overall RSS values, with strong positive correlation (r ≥ 0.75) for hands and fingers localizations in particular. In SSc patients with normal RSS values, the elastographic strain was significantly higher than in healthy controls. Elastographic strain of fingers' skin evaluated in SWE is highly accurate for distinguishing SSc patients (sensitivity 0.897-0.923, specificity 0.929-0.964, positive predictive value 0.946-0.973, negative predictive value 0.867-0.900). ESW results are substantially more reproducible than those of RSS examination (intraclass correlation coefficients: 0.987 vs. 0.941). The shear wave elastography is more reproducible and has higher sensitivity than RSS in the evaluation of skin condition in SSc, especially in case of changes non-detectable on physical evaluation, indicating it might become a useful tool in SSc diagnosis.

Correction to: Serum immunoglobulin G4 in Sjögren's syndrome: a pilot study.

In original article, a technical mistake went unnoticed by the authors. Throughout the article concentration unit of IgG4 is mistakenly reported as mg/dL instead of mg/L. The range of IgG4 concentration is mg/L.

Serum immunoglobulin G4 in Sjögren's syndrome: a pilot study.

Immunoglobulin IgG4 plays a role in the pathogenesis of the Mikulicz disease previously considered a form of primary Sjögren's syndrome (pSS). We investigated serum levels of IgG4, total IgG, C3, and C4 serum complementary components in patients suspected of Sjögren's syndrome. Basic laboratory and immunological tests, including IgG4 and IgG concentration, were performed on 20 healthy and 68 suspected of pSS individuals. We distinguished: group I: 48 pSS patients; group II (sicca): 20 patients with dryness without pSS. We revealed: statistical differences between groups I and II concerning hypergammaglobulinemia, ESR, RF, ANA, Ro, and La antibodies; lower IgG4 levels and IgG4/IgG ratio in group I compared to healthy individuals (p < 0.0435; 0.0035, respectively); no significant differences in the concentrations of IgG4 and IgG4/IgG ratio between sicca and control groups. significantly lower (p < 0.0002) C4 levels in group I compared to other groups; significant differences in C4 concentration and IgG4/IgG ratio between three groups (p = 0.0002 and p = 0.0090, respectively); a weak negative correlation between C4 and IgG (r =- 0.274) in the whole database; weak positive correlation between C4 and IgG4/IgG ratio (r = 0.237); a negative correlation of IgG4, IgG4/Ig ratio and C4 with focus score (r = - 0.281; r = - 0.327; r = - 0.406, respectively). IgG4 serum levels were significantly decreased compared to healthy subjects. IgG4 and C4 levels correlated with infiltrations in minor salivary glands. Hypergammaglobulinemia and decreased serum C4 component levels are typical for pSS.

The place of omega-3 and omega-6 acids in supplementary treatment of inflammatory joint diseases.

Eating habits have been analysed for years as a factor influencing the development of autoimmune diseases and susceptibility to infections. On the basis of research, observational studies and meta-analyses, special attention was paid to omega-3 and omega-6 acids. The purpose of the review is to show the importance of omega-3 and omega-6 acids as important ingredients in the healthy diet and as factors protecting against the development of the most common inflammatory rheumatic diseases. The influence of these omega-3 and -6 acids on the course of rheumatic diseases and arguments for their use as complementary therapy are also presented.

The role of Epstein-Barr virus infection in primary Sjögren's syndrome.

PURPOSE OF REVIEW: The purpose of this article is to draw attention to the role of Epstein-Barr virus (EBV) virus in the pathogenesis of the primary Sjögren's syndrome. The article introduces the problem of consequences of EBV acute infection, and its reactivation, in association with the immune response modulation by the virus and with an increased risk of developing systemic autoimmune diseases and EBV-associated cancers. RECENT FINDINGS: The knowledge about the mechanisms by which the virus may stay for years in a latent phase, unrecognized by the host response immune cells is constantly expanding. There are several mechanisms and theories about EBV influence on the autoimmune process in Sjogren's syndrome (pSS), including the similarity (molecular mimicry) between viral EBNA-2 protein and Ro-60 antigen or EBER-1 and EBER-2 viral proteins and La antigen. SUMMARY: The influence of EBV infection on the development and course of pSS has been proven. It has also been established that both EBV and pSS result in the increased risk of tumor (especially lymphoma) development. In the light of these findings, new ways to manage EBV infections are being sought. Optimal methods for assessing EBV infection status are being devised. Research also aims at finding therapies, which target EBV through the inhibition of the autoimmune process and of viral activity. The present article is an attempt to discuss the most important phenomena and elements linking EBV infection to the primary Sjögren's syndrome.

Rheumatology in Poland.

The aim of this article is to present the current state of rheumatology in Poland, including the scientific and clinical activity and essential aspects of Polish rheumatic patients' treatment. PubMed, Scopus and Web of Science databases were searched for main keywords: "rheumat*" and affiliation with Poland. Statistical data were obtained from the Central Statistical Office, the National Health Fund and the Polish Chamber of Physicians and Dentists, while the public information from the Polish Society for Rheumatology, the Ministry of Health and the Ministry of Science and Higher Education. Databases of the World Health Organization, the Organization for Economic Co-operation and Development and the European Statistical Office (Eurostat) were used. Most Polish rheumatologists work in large urban agglomerations in the Mazovian, Malopolskie and Silesian Voivodeships. The rheumatologic infrastructure includes 1713 working rheumatologists (> 30% exceeding the age of 60 years), 2301 hospital beds, 2279 outpatient clinics and 955 private practices. Poland's state funding is relatively limited, this problem being addressed by health officials with special treatment programs for biological drugs. The Eurostat data indicate, that in Poland, like in the majority of EU Member States, there's a tendency of specialist/general practitioner ratio rising. The number of scientific publications by Polish rheumatologists has steadily increased in recent years. Poland's rheumatology has made an enormous progress at all levels of functioning in recent decades. The EULAR recommendations are mostly incorporated into the Polish health system, leaving still room for its further improvement in the fields of financing, therapy and education.