Rheumatoid arthritis epidemiology: a nationwide study in Poland.

To assess the incidence and prevalence of rheumatoid arthritis (RA) in Poland for the period 2013-2021, total and dependent on gender, age, region and serological status. Information on reported National Health Fund (NHF) health services and reimbursed prescriptions were used, defining an RA patient as a person who had at least two visits in different quarters with ICD-10 code M05 or M06 and at the same time filled at least one reimbursed prescription for a drug whose active substance is methotrexate, sulfasalazine, leflunomide or was treated with biologic disease-modifying anti-rheumatic drugs (bDMRDs) or targeted synthetic DMARDs (tsDMARDs) as part of a drug program financed by the National Health Fund. The nationwide standardised incidence rate of RA in 2021 was 29 persons per 100,000 population (18 per 100,000 population of seropositive vs. 11 per 100,000 population of seronegative RA). The prevalence of RA in Poland in 2021 was 689.0 people per 100,000 population, a total of 0.7% (1.1% in women and 0.3% in men). The incidence of seronegative RA was approximately 38%. The majority of new RA diagnoses were in the sixth and seventh decades of life, irrespective of patients' gender. The results allow RA to be classified as a disease with a significant social impact. A trend of later onset of RA has been observed, which requires special consideration of the needs of patients over 55 years of age.

Acute Heart Failure in the Course of Macrophage Activation Syndrome Due to Newly Diagnosed Systemic Lupus Erythematosus: Case Presentation and Literature Review.

Macrophage activation syndrome is an uncommon yet dangerous and potentially fatal complication of many rheumatic diseases, inducing multiple organ failure, including, although rarely, acute heart failure. In the following paper, we present a case of a 37-year-old woman who, in a short period of time after a gynecological procedure due to fetal death, developed full-blown lupus erythematosus leading to early stages of macrophage activation syndrome with acute heart failure as its main clinical manifestation. We also include herein a brief literature review of the current understanding of diverse macrophage populations and their functions in various organs (focusing especially on the heart muscle), as well as a summary of different attempts at composing concise criteria for diagnosing macrophage activation syndrome.

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.

Fatigue in Inflammatory Joint Diseases.

Fatigue is a prevalent symptom in various rheumatic diseases, such as rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. It is characterised as a subjective, enduring feeling of generalised tiredness or exhaustion, impacting the patient's life quality and exacerbating disability. The fatigue nature is multifaceted, encompassing physiological, psychological, and social factors, and although the exact cause of inflammatory joint diseases is not fully understood, several factors are believed to contribute to its development. Despite high prevalence and importance, the symptom is often underestimated in clinical practice. Chronic inflammation, commonly associated with rheumatic diseases, has been proposed as a potential contributor to fatigue development. While current treatments effectively target inflammation and reduce disease activity, fatigue remains a persistent problem. Clinical evaluation of rheumatic diseases primarily relies on objective criteria, whereas fatigue, being a subjective symptom, is solely experienced and reported by the patient. Managing fatigue in inflammatory joint diseases involves a multifaceted approach. Identifying and comprehensively assessing the subjective components of fatigue in individual patients is crucial for effectively managing this symptom in everyday clinical practice.

Efficacy and safety of switching from reference adalimumab to CT-P17 (100 mg/ml): 52-week randomized, double-blind study in rheumatoid arthritis.

OBJECTIVE: To compare the safety and efficacy of switching from reference adalimumab to adalimumab biosimilar CT-P17 with continuing reference adalimumab/CT-P17 in active RA. METHODS: This double-blind, phase III study randomized (1:1) subjects with active RA to receive 40 mg (100 mg/ml) CT-P17 or European Union-sourced reference adalimumab subcutaneously every 2 weeks (Q2W) until week (W) 24 [treatment period (TP) 1]. Thereafter, subjects receiving reference adalimumab were randomized (1:1) to continue reference adalimumab or switch to CT-P17 from W26 (both Q2W until W48; TP2). Subjects receiving CT-P17 in TP1 continued CT-P17. W0-W24 results were previously reported; we present W26-W52 findings. End points were efficacy (including joint damage progression), pharmacokinetics, safety and immunogenicity. RESULTS: Of 607 subjects who initiated TP2 treatment, 303 continued CT-P17, 153 continued reference adalimumab and 151 switched to CT-P17. Efficacy improvements up to W24 were maintained during TP2; efficacy was comparable among groups. At W52, 20% improvement in ACR response rates were 80.5% (continued CT-P17), 77.8% (continued reference adalimumab) and 82.2% (switched to CT-P17). Joint damage progression was minimal. Mean trough serum adalimumab concentrations were similar among groups. CT-P17 and reference adalimumab safety profiles were numerically similar and switching did not affect immunogenicity. At W52, 28.4% (continued CT-P17), 27.0% (continued reference adalimumab) and 28.3% (switched to CT-P17) of subjects were anti-drug antibody-positive. CONCLUSION: Efficacy, pharmacokinetics, safety and immunogenicity of CT-P17 and reference adalimumab were comparable after 1 year of treatment, including after switching from reference adalimumab to CT-P17. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT03789292.

Role of Distinct Macrophage Populations in the Development of Heart Failure in Macrophage Activation Syndrome.

Macrophage activation syndrome (MAS) is one of the few entities in rheumatology with the potential to quickly cause multiple organ failure and loss of life, and as such, requires urgent clinical intervention. It has a broad symptomatology, depending on the organs it affects. One especially dangerous aspect of MAS's course of illness is myocarditis leading to acute heart failure and possibly death. Research in recent years has proved that macrophages settled in different organs are not a homogenous group, with particular populations differing in both structure and function. Within the heart, we can determine two major groups, based on the presence of the C-C 2 chemokine receptor (CCR2): CCR2+ and CCR2-. There are a number of studies describing their function and the changes in the population makeup between normal conditions and different illnesses; however, to our knowledge, there has not been one touching on the matter of changes occurring in the populations of heart macrophages during MAS and their possible consequences. This review summarizes the most recent knowledge on heart macrophages, the influence of select cytokines (those particularly significant in the development of MAS) on their activity, and both the immediate and long-term consequences of changes in the makeup of specific macrophage populations-especially the loss of CCR2- cells that are responsible for regenerative processes, as well as the substitution of tissue macrophages by the highly proinflammatory CCR2+ macrophages originating from circulating monocytes. Understanding the significance of these processes may lead to new discoveries that could improve the therapeutic methods in the treatment of MAS.

Aseptic Abscess Syndrome in Rheumatoid Arthritis Patient.

Aseptic abscess syndrome (AAS) is a rare, potentially life-threatening disorder, with numerous features of neutrophilic dermatoses. The main symptoms include aseptic abscess-like collections in internal organs (spleen, liver, lungs), lack of microbes (bacteria, viruses, or parasites) after an exhaustive search, ineffectiveness of antibiotics, and high sensitivity to corticosteroid therapy. AAS is characterized by the development of deep, inflammatory abscesses and systemic symptoms (weight loss, abdominal pain, fever, and leukocytosis). They may be associated with inflammatory bowel disease (IBD) and autoimmune diseases. The patient in this study is a 67-year-old man, suffering from rheumatoid arthritis (RA), with numerous purulent abscesses in the mediastinum, within the subcutaneous tissue above the extension surfaces of the joints, and on the dorsum of the hands. The lesions are accompanied by bone destruction. The patient was treated with prednisone 40 mg and adalimumab, which resulted in a quick reduction of inflammatory markers and clinical improvement, as well as the healing and absorption of abscesses. Despite COVID-19 infection, treatment with remdesivir, prednisone, and adalimumab was continued, with the complete resolution of the lesions. AAS is difficult to recognize, so practitioners have to be aware of this condition, especially in patients with RA.

The effect of therapy on TRM in psoriatic lesions.

Introduction: The course of psoriasis is associated with recurrence of the lesions at the same location despite effective treatment. It is due to the presence of TRM (tissue-resident memory cells) in the seemingly healthy skin, which may initiate an inflammatory cascade. Aim: The assessment of TRM in psoriatic lesions prior to and after 12 weeks of systemic therapy with methotrexate (MTX) or secukinumab (SEC) or ixekizumab (IXE) or adalimumab (ADA). Material and methods: TRM markers (CD4, CD8, CD103, CD69, CD49, CXCR6) and the tissue expression of cytokines (IL-17, IL-22) in the psoriatic lesions obtained from 13 patients compared to 10 healthy skin samples were evaluated with immunohistochemistry. Biopsy specimens were collected three times from the same psoriatic plaque before and after 4 and 12 weeks of therapy. Results: The expression of TRM markers in the lesions decreased at three time points (W0, W4, W12), revealing the diminished intensity of fluorescence over time with each therapy. The most rapid response was observed with anti-IL-17 therapy at W4 of treatment, while with MTX and ADA at W12. Conclusions: The decreased expression of TRM markers occurring predominantly in the lesional dermis and not in the epidermis over 12 weeks of observation may be due to the poorer penetration of systemic drugs to the epidermis, or the process of psoriatic lesion regression in the epidermis is secondary to the reduction of inflammation in the skin, or TRM in the epidermis may be more resistant to therapy.

Immunological Memory of Psoriatic Lesions.

The natural course of psoriasis is the appearance of new lesions in the place of previous ones, which disappeared after a successful therapy. Recent studies of psoriasis etiopathogenesis showed that after psoriatic plaques have disappeared, in healthy skin we can still find a trace of inflammation in the form of tissue resident memory cells (TRM). They are originally responsible for protection against viral and bacterial infections in non-lymphatic tissues. In psoriatic inflammation, they are characterized by heterogeneity depending on their origin. CD8+ T cells TRM are abundantly present in psoriatic epidermis, while CD4+ TRM preferentially populate the dermis. In psoriasis, epidermal CD8+ TRM cells express CLA, CCR6, CD103 and IL-23R antigen and produce IL-17A during ex vivo stimulation. However, CD4+ CD103+ TRM can also colonize the epidermis and produce IL-22 during stimulation. Besides T cells, Th22 and epidermal DCs proved that epidermal cells in healed skin were still present and functioning after several years of disease remission. It explains the clinical phenomenon of the tendency of psoriatic lesions to relapse in the same location and it allows to develop new therapeutic strategies in the future.

Psoriasis and systemic lupus erythematosus in children - literature review based on case report.

Immune-mediated inflammatory diseases are a group of diseases characterized by generalized inflammation that results from immune dysregulation, especially involving the mechanisms of acquired immunity. These diseases may be familial, showing that genetic factors play an important role in their development. Additionally, the occurrence of one disease makes a patient prone to other diseases. However, the coexistence of systemic lupus erythematosus (SLE) and psoriasis (Ps) is very rare due to their distinct genetic determinants and mechanisms of pathogenesis. Treatment is also challenging, as medications used to treat one condition exacerbate or even trigger the symptoms of the other. This paper presents the case of a Ps patient with a family history of autoimmune diseases, who developed systemic lupus erythematosus during puberty, as well as a discussion on the coexistence of SLE and Ps in developmental age based on available literature searching for PubMed database and American College of Rheumatology and European League Against Rheumatism abstracts particularly in this subject.

Prevalence and severity of fatigue in psoriasis and psoriatic arthritis.

INTRODUCTION: Fatigue is an important and underrated symptom of many chronic diseases. AIM: The evaluation of incidence and severity of fatigue as well as the influence of selected factors on fatigue in patients with psoriasis and psoriatic arthritis (PsA). MATERIAL AND METHODS: The study included 60 patients with PsA, 58 patients with psoriasis and 61 persons in the control group aged 35-70 years. Assessment of fatigue was conducted using a fatigue subscale from the FACIT-F questionnaire. Severity of skin lesions and arthritis was determined with PASI and DAS28, respectively, as well as the number of painful and swollen joints, severity of pain and inflammatory markers. RESULTS: Severe fatigue occurred in 17%, 28%, and 1.6% of patients with psoriasis, PsA and the control group, respectively. Severity of fatigue was significantly higher in patients with PsA as compared to patients with psoriasis (p < 0.0001). In patients with psoriasis and PsA, it decreased along with the duration of psoriasis (r = 0.291, p < 0.05 vs. r = 0.382, p < 0.05, respectively). No significant correlation was found between the duration of PsA and fatigue. After using the linear regression model, severity of fatigue in psoriasis was correlated with the age of patients and the duration of psoriasis, while in PsA, with the duration of psoriasis, PASI, DAS28, CRP and the number of painful joints. CONCLUSIONS: The results of this study may indicate the need for routine fatigue examination among people with psoriasis and psoriatic arthritis.

Role of Microparticles in the Pathogenesis of Inflammatory Joint Diseases.

Rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) make up a group of chronic immune-mediated inflammatory diseases (IMIDs). The course of these diseases involves chronic inflammation of joints and enthesopathies, which can result in joint damage and disability. Microparticles (MPs) are a group of small spherical membranous vesicles. The structure and cellular origin of MPs, mechanisms that stimulate their secretion and the place of their production, determine their biological properties, which could become manifest in the pathogenesis of immune-mediated inflammatory diseases. Microparticles can stimulate synovitis with proinflammatory cytokines and chemokines. MPs may also contribute to the pathogenesis of rheumatic diseases by the formation of immune complexes and complement activation, pro-coagulation activity, activation of vascular endothelium cells, and stimulation of metalloproteinase production. It seems that in the future, microparticles can become a modern marker of disease activity, a response to treatment, and, possibly, they can be used in the prognosis of the course of arthritis. The knowledge of the complexity of MPs biology remains incomplete and it requires further comprehensive studies to explain how they affect the development of rheumatic diseases. This review focuses on the immunopathogenic and therapeutic role of MPs in chronic immune-mediated inflammatory joint diseases.

Monostotic Paget's disease of bone - literature review and case report.

Paget's disease of bone (PDB) is a localized, chronic bone metabolic disorder, characterized by an osteoclastic malfunction, causing increased bone resorption and subsequent compensatory creation of new bone with a defective microstructure. Monostotic cases of PDB are less common than asymmetrical polyostotic PDB cases. The radiological diagnosis of PDB is usually straightforward, but monostotic cases can cause diagnostic difficulties. We report a case of monostotic PDB in a 64-year-old man. He experienced pain of the left lower extremity and radiological investigations revealed irregular areas of bone destruction in the left femur. Bone biopsy findings indicated PDB. Treatment with bisphosphonates was initiated, but after about three years of treatment left hip arthroplasty was required due to a large area of bone destruction. Presentation of this case report aims to discuss diagnostic challenges of monostotic cases of PDB and present guidelines of treatment.

Cutaneous polyarteritis nodosa in a 7-year-old boy: difficulties in diagnosis.

Vasculitides are a diverse group of diseases. The potential diversity of their clinical symptoms requires the exclusion of other systemic connective tissue diseases, infectious diseases or malignancies. Due to similar clinical manifestations, comprehensive differential diagnosis is needed. This paper presents the case of a boy in whom polyarteritis nodosa, early stage of Behçet's disease or autoimmune/autoinflammatory syndrome induced by adjuvants was suspected following initial diagnostics. He was ultimately diagnosed with cutaneous polyarteritis nodosa.

Articular Cartilage Aging-Potential Regenerative Capacities of Cell Manipulation and Stem Cell Therapy.

Changes in articular cartilage during the aging process are a stage of natural changes in the human body. Old age is the major risk factor for osteoarthritis but the disease does not have to be an inevitable consequence of aging. Chondrocytes are particularly prone to developing age-related changes. Changes in articular cartilage that take place in the course of aging include the acquisition of the senescence-associated secretory phenotype by chondrocytes, a decrease in the sensitivity of chondrocytes to growth factors, a destructive effect of chronic production of reactive oxygen species and the accumulation of the glycation end products. All of these factors affect the mechanical properties of articular cartilage. A better understanding of the underlying mechanisms in the process of articular cartilage aging may help to create new therapies aimed at slowing or inhibiting age-related modifications of articular cartilage. This paper presents the causes and consequences of cellular aging of chondrocytes and the biological therapeutic outlook for the regeneration of age-related changes of articular cartilage.

Sleep disorders in patients with psoriatic arthritis and psoriasis.

OBJECTIVES: To assess and measure occurrence of sleep disorders in patients with psoriatic arthritis (PsA) and psoriasis (Ps). MATERIAL AND METHODS: The study included 62 patients with psoriatic arthritis and 52 patients with psoriasis. The measurement of sleep quality was conducted using the Pittsburgh Sleep Quality Index (PSQI), the evaluation of fatigue by the fatigue subscale of the FACIT-F questionnaire and the patient's quality of life by the Health Assessment Questionnaire (HAQ). The psoriasis severity was determined using the Psoriasis Area Severity Index (PASI) and the activity of arthritis by the disease activity score of 28 joints (DAS 28). The Visual Analogue Scale (VAS) was used to assess the severity of pain. RESULTS: Poor sleep quality was found in 67.7% of PsA patients, 57.7% in Ps patients and 14.6% within the control group. Sleeping disorders in patients with PsA and Ps were related to worse quality of life and intense fatigue. Methotrexate treatment was not related to sleeping disorders, but an improvement in sleep quality was observed in both PsA and Ps patients who were treated with anti TNF-α antibodies (p < 0.001 and p = 0.032 respectively). Following the use of the linear regression model, the following factors worsen the sleep quality in PsA: pain (R2 = 0.462, p < 0.001), tender joint count (R2 = 0.434, p < 0.001), C-reactive protein (CRP) concentration (R2 = 0.391, p < 0.001), patient's age (R2 = 0.284, p = 0.003) and duration of psoriasis (R2 = 0.166, p = 0.006). In Ps patients the factors were: severity of skin lesions (R2 = 0.329, p < 0.001), duration of psoriasis (R2 = 0.290, p = 0.004) and patient's age (R2 = 0.282, p = 0.019). CONCLUSIONS: Poor sleep quality in patients with PsA or Ps is a common symptom. Sleep disorders are more frequent in patients with PsA than in those with psoriasis.

Role of Stem Cells in Pathophysiology and Therapy of Spondyloarthropathies-New Therapeutic Possibilities?

Considerable progress has been made recently in understanding the complex pathogenesis and treatment of spondyloarthropathies (SpA). Currently, along with traditional disease modifying anti-rheumatic drugs (DMARDs), TNF-α, IL-12/23 and IL-17 are available for treatment of such diseases as ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Although they adequately control inflammatory symptoms, they do not affect the abnormal bone formation processes associated with SpA. However, the traditional therapeutic approach does not cover the regenerative treatment of damaged tissues. In this regards, stem cells may offer a promising, safe and effective therapeutic option. The aim of this paper is to present the role of mesenchymal stromal cells (MSC) in pathogenesis of SpA and to highlight the opportunities for using stem cells in regenerative processes and in the treatment of inflammatory changes in articular structures.

Stem Cells as Potential Candidates for Psoriasis Cell-Replacement Therapy.

Recent years have seen considerable progress in explaining the mechanisms of the pathogenesis of psoriasis, with a significant role played in it by the hyper-reactivity of Th1 and Th17 cells, Treg function disorder, as well as complex relationships between immune cells, keratinocytes, and vascular endothelium. The effect of stem cells in the epidermis and stem cells on T cells has been identified and the dysfunction of various types of stem cells may be a prime cause of dysregulation of the inflammatory response in psoriasis. However, exploring these mechanisms in detail could provide a chance to develop new therapeutic strategies. In this paper, the authors reviewed data on the role played by stem cells in the pathogenesis of psoriasis and initial attempts at using them in treatment.

[Osteoporosis and vascular calcification in rheumatoid arthritis - the role of osteoprotegerin and sclerostin]. / Osteoporoza i kalcyfikacja naczyn w reumatoidalnym zapaleniu stawów ­ rola osteoprotegeryny i sklerostyny.

Disorders of bone tissue metabolism and increased frequency of cardiovascular diseases are among the well-known, extra-articular complications of rheumatoid arthritis (ra). The mechanisms leading to local and generalized loss of bone tissue as well as those promoting calcification of vessels are similar. Recently, a great interest has aroused among the studies related to the meaning of the RANKL/RANK/OPG system and the Wnt/ß-catenin signaling pathway, as biological links between the bone and vascular systems. In the course of ra, lowering of the mineral density of bones and intensification of vascular calcification seem to be associated with the increase of plasma concentration of osteoprotegerin (OPG) and sclerostin - the regulatory proteins of the RANKL/RANK/OPG system and the Wnt/ß-catenin pathway. Molecular mechanisms associated with the osteoblasts' activation and repression of bone resorption in the future can become the target of a precise, combination therapy in osteoporosis and calcification changes. The article presents the role of the RANKL/RANK/ OPG system and the Wnt/ß-catenin pathway in the pathogenesis of disorders of bone tissue metabolism and calcification of vessels in ra, with particular emphasis on the role of OPG and sclerostin.

[The role of the human microbiom in the pathogenesis of rheumatoid arthritis - a literature review].

Rheumatoid arthritis is a chronic, progressive, autoimmune disease with numerous articular, extra-articular and systemic manifestations. The cause of rheumatoid arthritis is multifactorial including genetic and environmental factors. Recent advantages in sequencing techniques have allowed the deep characterization of the human microbiota. Available evidence confirms the existence of an association between dysbiosis and rheumatoid arthritis but it still remains unclear whether alterations in the microbiome are a pathogenic cause or an effect of autoimmune disease. In patients with rheumatoid arthritis the most supported association between disease and microbiota is with the oral dysbiosis usually observed in patients with periodontitis. Given the strong variability and abundance of microbes living in close relation with human host, it becomes a difficult task to define what should be considered the favorable microbiome. There is need for broader studies to establish how the human microbiome contributes to disease susceptibility, and to characterize the role of microbial diversity in the pathogenesis of rheumatoid arthritis, disease manifestation, and progression. The identification of dysbiosis specific for rheumatoid arthritis and the understanding of the dynamic interaction between microbiota and their host may help in establishing an individualized management for each patient with rheumatoid arthritis, and achieve a better efficacy of the therapy.