Correlation between pathogenetic factors and vascular endothelial damage in patients with rheumatoid arthritis
Introduction
Systemic rheumatoid vasculitis accounts for 1 to 5% of complications seen in rheumatoid arthritis, while autopsy studies report an average of 23% incidence. This enormous difference in numbers emphasizes the rate of misdiagnosis or underdiagnosis of systemic rheumatoid vasculitis. It mainly affects people with a median age of 65 years. It is particularly noteworthy, as systemic rheumatoid vasculitis has a high mortality and relapse rate. Also, the multifactorial aetiology: cytokines/immune cells and other particles determines clinical complexity of this type of angiitis.
Materials and methods
A comprehensive literature search of articles published since 1996 was conducted using MEDLINE via PubMed and HINARI. The search included terms such as "rheumatoid vasculitis", "rheumatoid arthritis", and "endothelial dysfunction", focusing on mechanisms driving vascular damage. A total of 217 relevant sources were identified, including original studies, reviews, and book chapters. The study evaluated pathogenic factors like cytokines, immune complexes, and systemic inflammation, highlighting their roles in endothelial dysfunction and hypercoagulability.
Results
The main pathogenetic factors in systemic rheumatoid vasculitis were immune complexes, cytokines (IL-6/TNF-α and IL-17), immune and blood cells (CD20/TH17/Platelets) and others (microparticles, blood rheology modifications). Even though, taken separately, those factors appear to have little to no impact on vascular endothelium, their synergistic effect lead to significant endothelial damage.
Conclusions
To conclude, each disease has its own pathogenetic factors which determine the natural course of this pathology. Understanding these mechanisms plays an important role for clinicians helping them to diagnose and effective treatment. Taking into consideration the relationships between specific factors in rheumatoid angiitis, we can make more specific decisions for its diagnosis and treatment. We can also use the pathophysiology of systemic rheumatoid vasculitis as a foundation for developing prevention measures.
The role of autoantibodies in neuropsychiatric systemic lupus erythematosus: mechanisms, biomarkers and clinical correlations
Abstract
Introduction
Neuropsychiatric lupus erythematosus is still a disease with a very challenging diagnostic process, lacking high specificity and sensitivity assays. Autoantibodies can change this perspective, and because of their pathogenetic involvement, can become a very powerful tool for early detection and disease activity tracking. However, their biomarker potential still needs further evaluation. In this study, we focused on the pathogenetic mechanisms of neuropsychiatric lupus erythematosus and the involvement of brain-specific and systemic autoantibodies in the development of neuropsychiatric manifestations.
Material and methods
Medical articles addressing the correlation of autoantibodies concentrations in serum and cerebrospinal fluid and their potential pathogenetic mechanism, were reviewed. More than 100 articles were identified from databases such as PubMed, ScienceDirect, Frontiers, and Wiley, using keywords such as “neuropsychiatric lupus erythematosus”, “autoantibodies”, “pathogenesis”, “biomarker” and “neuropsychiatric manifestations”. From these, 47 articles were selected for the current review.
Results
Autoantibodies truly are indeed a tool in the diagnostic process of neuropsychiatric lupus erythematosus, and many researchers have obtained statistically valid correlations between their presence and specific neuropsychiatric manifestations. Variations in their concentration not only reflect the disease activity but also the fact that they are involved in its development through interactions with neuronal and vascular targets. Besides autoimmunity, brain-blood barrier dysfunction is also another key part of the pathogenetic mechanism, with markers of this injury also being useful in the diagnostic methodology. With future research, specific combinations of these markers can be linked to distinct clinical manifestations by creating multi-biomarker panels, a robust framework for diagnosing neuropsychiatric lupus erythematosus.
Conclusions
Neuropsychiatric lupus erythematosus remains a condition that highly challenging to diagnose and manage due to the heterogeneity of symptoms and the lack of standardized diagnostic tools. Autoantibodies, along with other markers of vascular and inflammatory injury can aid specialists in dealing with this disease, but further research is needed to validate these biomarkers in diverse patient populations and to standardize assays for clinical application to improve the early detection and management of NPSLE, ultimately enhancing patient outcomes and quality of life.
Introduction
Axial spondylitis is a chronic inflammatory disease primarily affecting the axial skeleton but can also involve peripheral joints. Axial spondylitis is often associated with extra-articular manifestations, such as inflammatory bowel diseases, emphasizing the need for rigorous monitoring and personalized therapeutic approaches. The interactions between axial spondylitis and inflammatory bowel diseases fall under the concept of “immune-mediated inflammatory diseases”, sharing common pathogenetic mechanisms. This study analyzes the prevalence and characteristics of inflammatory bowel diseases in patients with axial spondylitis.
Objective
The objective of this study was to describe the baseline characteristics of patients with axial spondylitis, evaluate the prevalence of inflammatory bowel diseases in this population, and identify correlations between the two conditions, contributing to a better understanding of their pathogenetic and clinical interactions.
Materials and methods
This prospective observational study included 257 axial spondylitis patients followed over two years. Patients were selected according to ASAS criteria for axial spondylitis and clinical guidelines for inflammatory bowel diseases. Analyses included clinical evaluations, laboratory tests, and imaging studies. Data were processed using SPSS v22.0. Continuous variables were expressed as mean ± standard deviation or median and interquartile range, and categorical variables as percentages. Correlations were assessed using Spearman’s coefficient, with results considered significant at p<0.05.
Results
Among the 257 patients included (168 men and 89 women, mean age 48.2 ± 13.1 years), 13.2% were recently diagnosed with axial spondylitis. Of these, 5.1% had inflammatory bowel diseases, distributed as follows: Crohn's disease (3.1%), ulcerative colitis (1.2%), and indeterminate colitis (0.8%). In 53.8% of cases, the diagnosis of inflammatory bowel diseases preceded axial spondylitis. Multivariate analysis identified the absence of a family history of axial spondylitis as a significant risk factor for inflammatory bowel diseases (OR = 3.4; p = 0.025). The prevalence of inflammatory bowel diseases increased with axial spondylitis duration, reaching 6.5% in patients with disease progression over eight years.
Conclusions
The study highlights a high prevalence of inflammatory bowel diseases in axial spondylitis patients, indicating the need for rigorous clinical monitoring. The absence of a family history of axial spondylitis was identified as a major risk factor for inflammatory bowel diseases. These findings emphasize the importance of a multidisciplinary clinical approach, including active screening for inflammatory bowel diseases and collaboration between rheumatologists and gastroenterologists, to improve patient prognosis and quality of life.
Osteitis condensans ilii – difficulty in diagnosis and management. Clinical case study
Introduction
Osteitis condensans ilii (OCI) is a condition characterized by benign sclerosis of the iliac bone in the portion adjacent to the sacroiliac joints, which is radiologically manifested by triangular opacities at the level of this portion. Among the clinical manifestations, localized low back or lumbosacral pain is often attested, which is found in the gestational or post-partum period. The pain may worsen during physical exertion or during menstruation and may be accompanied by myalgia.
Material and methods
The epidemiological, clinical and paraclinical data were used to highlight this study, followed by the conclusions of multidisciplinary specialists, retrieved from the inpatient medical records of 3 women with OCI, who were admitted for diagnosis and treatment.
Results
3 cases of imaging-determined OCI will be presented, which were initially diagnosed with seronegative spondyloarthritis (SpA). Through them, we would determine the varieties between the OIC forms and their differential diagnosis with SpA. The results of the lab tests do not reveal specific changes, so the markers of inflammation (C-reactive protein, erythrocyte sedimentation rate) were normal. Also, unlike SpA, the marker HLA-B27 is in most cases negative.
Conclusions
According to the results of the presented clinical cases, OCI is often confused with sacroiliitis, which leads to misdiagnosing and erroneous treatment tactics. Thus, in order to establish a true diagnosis, it is necessary to collect a detailed history, perform a comprehensive objective examination, which includes the character of the pain and its triggers, the lack of inflammatory lab markers and the radiological presence of the sclerosis areas at the level of the iliac bone, not involving the sacroiliac joints.
Immune and mathematical procedures in early diagnosis of psoriatic and seronegative rheumatoid arthritis
Objectives
Improvement of early diagnosis of psoriatic arthritis based on clinical data, immunological and mathematical research methods.
Material and methods
The study was carried out between 2019 and 2022 at the Rheumatology and Nephrology Discipline, in the arthrology and rheumatology departments of the Timofei Moşneaga Republican Clinical Hospital. To accomplish the tasks set out in the study, 110 patients were examined, including 55 patients with psoriatic arthritis (group I) and 55 patients with rheumatoid arthritis (group II).
Results
The range with the highest probability of psoriatic arthritis for the instrumental index is between 0.54 and 1.86. Of the 55 patients with psoriatic arthritis in 95% of patients clinical, laboratory, immunological and instrumental indices were within the range of the highest probability of the disease, which indicates a fairly high reliability of the mathematical model.
Conclusions
Immune disorders in the early stages of rheumatoid arthritis and psoriatic arthritis are nonspecific and are characterized by an increase in CD16+ (26.2±1.5) and CD29+ (24.8±2.1) in rheumatoid arthritis, which is significantly higher than in psoriatic arthritis CD16+ (22.0±1.3) and CD29+ (17.4±3.2) (p <0.05). A mathematical model of rheumatoid arthritis and psoriatic arthritis has been developed, which serves as an additional way of diagnosing rheumatoid arthritis and early psoriatic arthritis.
Novel biomarkers in systemic sclerosis
Introduction
Due to the heterogeneous nature of systemic sclerosis, it is difficult to predict disease progression and complications. Despite the discovery of novel autoantibodies associated with systemic sclerosis (SSc), there is an unmet need for biomarkers for diagnosis, disease progression, and response to treatment.
Materials and methods
An analytical, qualitative study was performed with a narrative review of literature in the form of a synthesis article. Relevant primary sources published in 2020-2022 were identified and selected, using data extraction and analysis.
Results
Anti-citrullinated protein/peptide antibody could be useful in identifying patients with a more prominent joint disease. Of most interest, the anti-carbamylated protein antibodies (anti-CarP) could be a relevant biomarker related to fibrotic skin and lung disease. Positive anti-RNA (Ribonucleic acid) polymerase III antibody and antinuclear antibodies (ANA) negativity were significantly associated with GAVE (gastral antral vascular ectasia). Autoantibodies against telomeres may help identify systemic sclerosis with lung disease. Osteopontin links myeloid activation and disease progression in systemic sclerosis. CTRP (C1q tumor necrosis factor-related proteins) 9 protein levels may be biomarker of lung disease severity. CD (cluster differentiation) 21-low B cells are linked to vascular damage. L-tyrosine, L-tryptophan, and 1-methyl-adenosine distinguished healthy controls from SSc patients. L-leucine, L-isoleucine, xanthosine, and adenosine monophosphate differentiated between progressing and stable SSc-ILD. CECs (circulating endothelial cells) are a direct indicator of systemic vascular damage. Levels of the protein, galectin-3, are associated with heart involvement in people with systemic sclerosis. Low levels of the galectin-10 protein (Gal-10) in scleroderma associate with inflammation and vascular changes in the lungs, leading to pulmonary arterial hypertension (PAH). High levels of the CD146 protein may be a potential biomarker in identifying people with systemic sclerosis. Blood levels of the protein endocan increased in scleroderma patients who are at risk for pulmonary arterial hypertension . FLCs (free light chain) could be employed as useful potential biomarker of early diagnosis and to follow disease activity.
Conclusions
Novel discovered biomarkers could predict disease development, activity, and severity of diverse organ involvement, predict risk of complications of systemic sclerosis.
Improvement of early diagnosis of axial spondyloarthritis in intestinal infectious diseases
Introduction
Despite numerous fundamental clinical studies on the frequency, pathogenesis, clinical features of spondyloarthritis (SpA) in intestinal infectious diseases (IID) and intestinal damage in SpA, there are currently a number of unresolved problems, one of which is the problem of early diagnosis of arthropathies, especially associated with IID, which makes it necessary to continue the research in the scientific problem.
Purpose of the study
Appreciation of the features of early manifestations of axial arthropathies in intestinal infectious diseases in order to improve their early diagnosis.
Objectives of the study
Identification of clinical variants of axial arthropathies in patients with infectious intestinal diseases and instrumental description of axial lesion by conducting comparative analysis of clinical and laboratory parameters in these patients depending on the presence of axial arthropathies. Development of an algorithm for the early detection of axial spondyloarthritis in intestinal infectious diseases.
Material and methods
During 2015-2021, 141 patients were analyzed retrospectively, out of which 50 patients with SpA from the Republican Clinical Hospital „Timofei Moşneaga” and 91 patients with infectious intestinal diseases from the gastro-enterology and hepatology departments of the Republican Clinical Hospital „Timofei Moşneaga”. Depending on the etiology of IID, subjects were divided into 2 groups: the first group included patients with Yersinia enterocolitica or Campylobacter jejuni (Y±C), the second with Salmonella enteritidis or Shigella flexneri (S±Sh).
Results
In patients with IID, the following clinical variants of arthropathies have been identified: axial lesion (spinal inflammatory pain according to ASAS criteria (2009) in 42.9%, axial spondyloarthritis (axSpA) in 28.6%, AS in 15.4%), arthralgia - 38.5%, arthritis - 13.2%. Conventional radiography imaging and magnetic resonance imaging (MRI) of the sacroiliac joints (SI) increased the incidence of SpA from 6.6% (n = 6) to 28.6% (n = 26).
Conclusions
In patients with IID, the following clinical variants of arthropathies have been identified: axial lesion (spinal inflammatory pain according to ASAS criteria (2009) in 42.9%, axSpA in 28.6%, ankylosing spondylitis in 15.4%), arthralgia – 38.5%, arthritis – 13.2%. Imaging in the form of conventional radiography and MRI of SI joints increased the incidence of SpA from 6.6% (n = 6) to 28.6% (n = 26). Axial arthropathies, arthralgia, arthritis, and uveitis are encountered more frequently. At the same time, the possibility of detecting axSpA is greater if arthritis, arthralgia, inflammatory back pain, uveitis is present. Patients with S±Sh have a higher chance of developing axSpA compared to patients with Y±C.
Expressions and difficulty of clinical manifestations in the early diagnosis of psoriatic arthritis
Objectives
Study of clinical manifestations in psoriatic arthritis: enthesitis, dactylitis, peripheral arthritis, axial arthritis, skin manifestations, for early diagnosis, which would allow the establishment of an adjusted treatment and the elaboration of measures to prevent complications.
Materials and methods
The performed clinical study has an analytical-observational retrospective and included the patients who were hospitalized in the Rheumatology and Arthrology departments of the “Timofei Moşneaga” Republican Clinical Hospital during 2015-2021. The study included 103 patients with psoriasis (47 men and 56 women) with various clinical forms of psoriasis and different ages.
Results
The clinical examination of primary or referred patients with cutaneous manifestations, revealed peripheral arthritis in 15 patients (24.6%), dactylitis – in 37 (60.7%), heel pain was detected in 32 (52.5%), axial arthritis – in 30 (49.2%), enthesitis, distal interphalangeal arthritis and tendonitis were not detected. Those who primary or referred with joint manifestations, in 35 (57.4%) of patients was present peripheral arthritis, dactylitis in 40 (65.6%), enthesis of the elbow joints in 11 (18%), knee joints - in 8 (13.1%), the calcaneal region - to 25 (41%), arthritis of the distal interphalangeal joints was detected in 21 (34.4%), tendinitis - to 13 (21.3%).
Discussions
The obtained results allow us to state that one of the directions in improving the diagnosis of PsA consists in the use of ultrasound examination and MRI imaging of the joints of the hands and feet. This makes it possible to effectively identify the characteristic of enthesopathy, edema of tissues, as well as destructive changes in the joints of the hands and feet.
Conclusions
In the study group of patients with psoriasis, in 25 (24.2%) no joint damage was detected. The frequency of detection of psoriatic arthritis and other rheumatic diseases (rheumatoid arthritis, osteoarthritis, ankylosing spondylitis etc.) was 59.2% and 16.6%, respectively, 32 (52.5%) out of 61 (59.2%) patients with PsA were primarily diagnosed. The sensitivity and specificity of the mPEST (Psoriasis Epidemiology Screening Tool) questionnaire in relation to the CASPAR criteria were 77% and 69% respectively. The highest indicators of sensitivity, specificity and accuracy in the diagnosis of PsA has ultrasound and MRI: 88%, 92%, 89% and respectively, 89%, 94%, 91%
Clinical heterogeneity in the early diagnosis of psoriatic arthritis
Introduction
PsA are included in the group of HLA-B27-associated joint diseases, united in the group of seronegative spondylitis (SSA). At the same time, this disease differs from ankylosing spondylitis and other spondylitis with a particularly diverse clinical picture and the existence of only the syndromes inherent in it, for example, intermittent synovitis, palindromic rheumatism or mutilating arthritis.
Purpose of the study
Research of clinical heterogeneity of early psoriatic arthritis and the possibility of early diagnosis.
Materials and methods
The current study included 104 patients with PsA who were admitted to the rheumatology and arthrology departments of the IMSP Republican Clinical Hospital „Timofei Moşneaga” from 2003 to October 2021.
Results
The frequency of expression of individual clinico-anatomical variants of joint syndrome was different in patients with PsA-e and PsA-t (in PsA-e compared to PsA-t, the oligoarticular variant was significantly more likely to be observed (43.1% and 19%, respectively, p=0.01) and less often the variant of spondyloarthritis (7.8% and 19%, p=0.1), while the variant of polyarthritis (33.3% and 38%, p = 0,6) and distal interphalangeal (15,7% and 15%, p=0,9) were detected with the same frequency, as regards the mutilating variant, this was observed only in PsA-t.
Conclusions
The early stage of psoriatic arthritis is characterized by pronounced heterogeneity of manifestations of joint syndrome and damage to the tendon-ligament apparatus. In PsA-e oligoarthritis and polyarticular variants are the most common, less often - distal interphalangeal and spondyloarthritic. In the first 3 months after the onset of clinical manifestations of PsA, oligoarthritis was observed in 75.4% of patients and polyarthritis in 14% (p=0.0001), and after 6 months - 63% and 26.6% respectively (p=0.001). With a progression of the duration of the disease, the number of patients with arthritis increased, and by the end of the 2nd year was determined in 47.6% of patients, and oligoarthritis - in 28.6%.
Trigger impact of Chlamydia trachomatis on various types of seronegative spondyloarthritis
Introduction
To date, clinical manifestations, laboratory changes and the results of instrumental examinations of the joints and spine in axial seronegative spondyloarthritis (aSpA) caused by Chlamydia trachomatis have not been fully elucidated.
Purpose of the study: evaluation of clinical manifestations features, diagnosis, and evolution of seronegative spondyloarthritis associated with Chlamydia trachomatis infection.
Objectives of the study: To compare clinical manifestations, changes in laboratory parameters, results of instrumental examinations of the joints and spine in seronegative spondyloarthritis, the axial, peripheral, and mixed form. To appreciate the significance of Chlamydia trachomatis in the development of SpA by detecting the presence of DNA using the polymerase chain reaction (PCR) in real time and by isothermal amplification of NASBA-PCR (Nucleic acid sequence-based amplification).
Material and methods
During 2015-2021 were examined 138 patients with SpA hospitalized in the Republican Clinical Hospital „Timofei Moşneaga”. Chlamydia trachomatis in the form of monoinfection was detected in 87 (6.3%) patients, of which 52 (59.8%) were women and 35 (40.2%) men.
Results
The results of the diagnosis of Chlamydia trachomatis infection in patients with arthritis: Chlamydia trachomatis infection was detected in 78 (89.7%) out of 87 patients examined by PCR, and in 9 (10.3%) cases by ELISA. The peripheral form begins mainly with inflammation of the joints of the lower extremities (81.8%), of which the knee joints are mainly involved in the pathological process (63.6%). SpA axial form associated with Chlamydia trachomatis infection occurs mainly in young men (85.7%). In more than half of the patients, large joints participate in the pathological process (58.8%), especially the lower extremities. The axial variant of the SpA can begin with an injury in any part of the spine.
Conclusions
SpA associated with Chlamydia trachomatis infection has more expressed clinical, laboratory and instrumental manifestations both in the onset and in the advanced stage of the disease.