Severe Joint Damage Research Articles

AN EVALUATION OF DIETARY APPROACHES USED IN THE CLINICAL MANAGEMENT OF RHEUMATOID ARTHRITIS

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by systemic inflammation, persistent synovitis, and other comorbidities, that affects 0.5-1.0% of the overall population. Long-term active RA causes severe joint damage, disabling pain and diminished life quality. The etiology of RA is not accurately understood, but it is thought to be due to an interaction between the responses of the innate and acquired immune systems. RA is characterized by the presence of Rheumatoid Factor (RF) and anti citrullinated peptide antibodies in the blood circulation. Also the composition of intestinal the gut microbiome is claimed to be critical in immune responses associated with RA. Changes in the microbiota are thought to be related to the risk and severity of the disease. Three regions; primarily the lungs, oral mucosa and gastrointestinal tract have been associated with changes in the microbiota. Commonly, the pharmaceutical treatment of RA includes non-steroidal anti-inflammatory drugs (NSAIDs) that are used to manage the pain and inflammation associated with RA and disease-modifying anti-rheumatic drugs that reduces pain by slowing down the disease. Unfortunately, remission is not likely in many patients. Moreover, side effects related to drugs are commonly reported. Some alterations in the patients’ life and environment are thought to aggravate symptoms, thus influencing severity of RA. For example RA patients, the participants asserted that consumption of red meat, alcoholic and non-alcoholic beverages worsen their symptoms, while nutrients such as fish and blueberries help alleviate the symptoms. To manage the adverse effects of RA, particular dietary alterations are suggested to be effective in reducing inflammation, increasing antioxidant levels, and improving lipid profiles. Antigenic load and food intolerance are thought to play a role in both the onset of Rheumatoid Arthritis. Besides, it has been shown that the intestinal mucosa of the patients would have become more permeable to allergens due to long term NSAIDs use. In this sense, Elimination Diet, Mediterranean Diet, Vegan/Vegetarian Diet approach, Omega-3 Fatty acids, Vitamin D and probiotic supplementation is thought to reduce disease activity. The purpose of this review is to evaluate the efficiency of certain dietary approaches and supplements used for lessening the RA related symptoms, based on the scientific evidence found in the literature.

ОКИСНА МОДИФІКАЦІЯ БІЛКІВ У СИНОВІАЛЬНІЙ РІДИНІ ХВОРИХ НА ОСТЕОАРТРИТ ПІСЛЯ SARS-CoV2-ІНФЕКЦІЇ

The pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made a serious public health threat worldwide. It has caused many complications and deaths, so millions of people are at risk in more and more countries. A special group consists of patients with chronic diseases, particularly osteoarthritis. It is known that the development of osteoarthritis is associated with oxidative stress and excessive production of free radicals. Proteins are highly sensitive to free radical oxidation, so their oxidation level reflects the oxidant-antioxidant balance in the body. The aim of the work was to determine the concentration of products of oxidative modification of proteins and sulfhydryl groups in the synovial fluid of patients with osteoarthritis after SARS-CoV2 infection. All study participants were divided into two groups. The first group (n=22) is patients with osteoarthritis of the knee joints II-III degree. The second group (n=14) is patients with osteoarthritis of the knee joints II-III degree, who suffered a mild and moderate form of COVID-19 6-9 months ago. In the conducted studies, the products of protein oxidation in the synovial fluid of patients of all experimental groups were evaluated. The concentration of products of oxidative modification of proteins was determined by the level of carbonyl derivatives, which are detected in the reaction with 2,4-dinitrophenylhydrazine. The concentration of total, protein-bound and non-protein sulfhydryl (SH) groups was measured by the Ellman method. Processing of research results was carried out using generally accepted methods of variational statistics. It was established that in the synovial fluid of patients with osteoarthritis of the knee joints who contracted COVID-19, the concentration of products of oxidative modification of proteins increased. Under the same experimental conditions, the concentration of sulfhydryl groups decreased. The detected changes indicate a violation of the oxidant-antioxidant balance in the synovial fluid of patients with osteoarthritis after SARS-CoV-2 infection. This indicates the prevalence of free radical processes and the development of oxidative stress directly in the joint. Our results indicate that patients with osteoarthritis may develop more severe joint damage after infection with COVID-19.

SUBCUTANEOUS TREATMENT MODALITIES IN HEMOPHILIA CARE IN 2022

Hemophilia is a rare hereditary, recessive X-linked, hemorrhagic disorder characterized by deficiency of coagulation factor VIII (hemophilia A) or IX (hemophilia B). A typical presentation of this disease is spontaneous or traumatic bleeding. Although bleeding can occur in any part of the body, the most frequently affected parts are the joints and muscles. Bleeding into the joints (hemarthrosis) can lead to stiffness, pain, swelling and severe joint damage which can cause the patient severe long-term disability and potentially death if untreated. A while ago, prophylaxis with factor concentrates started at an early age in children with severe or moderate hemophilia, has proven its efficacy over on demand treatment in minimizing the hemorrhagic risk and so the long-term sequelae. Subsequently, after the introduction of extended half-life factor concentrates, patients are living longer and ‘’better’’ as a result of safer factor concentrates, and less treatment burden on young patients. Despite the great efforts of clinical research, until recently there were no treatments other than replacement factors. Lately, “non-factor therapies ” gained their place in the treatment armamentarium of hemophilia. Those are medications that improve hemostasis without replacing the missing factor. These therapies are all designed to be given subcutaneously and at relatively infrequent intervals and thus reducing the treatment burden. The aim of our presentation is to shed the light on different families of “non-factor therapies”: bispecific monoclonal antibody like emicizumab (approved and available to clinicians for the subcutaneous treatment of hemophilia A) and MIM8 (under investigation), rebalancing agents like fitusiran (an antithrombin inhibitor) and the anti-TFPI (Tissue Factor Pathway Inhibitor) antibodies, as marstacimab or concizumab .

Rheumatoid arthritis: advances in treatment strategies.

Rheumatoid arthritis (RA) is characterised by severe joint and bone damage due to heightened autoimmune response at the articular sites. Worldwide annual incidence and prevalence rate of RA is 3 cases per 10,000 population and 1%, respectively. Several genetic and environmental (microbiota, smoking, infectious agents) factors contribute to its pathogenesis. Although convention treatment strategies, predominantly Disease Modifying Anti Rheumatic Drugs (DMARDs) and Glucocorticoids (GC), are unchanged as the primary line of treatment; novel strategies consisting of biological DMARDs, are being developed and explored. Personalized approaches using biologicals targetspecific pathways associated with disease progression. However, considering the economic burden and side-effects associated with these, there is an unmet need on strategies for early stratification of the inadequateresponders with cDMARDs. As RA is a complex diseasewith a variable remission rate, it is important not only to evaluate the current status of drugs in clinicalpractice but also those with thepotential ofpersonalisedtherapeutics. Here, we provide comprehensive data on the treatment strategies in RA, including studies exploring various combination strategies in clinical trials. Our systematic analysis of current literature found that conventional DMARDs along with glucocorticoid may be best suited for early RA cases and a combination ofconventional and targetedDMARDs could be effective for treating seronegative patients with moderate to high RA activity. Clinical trials with insufficient responders to Methotrexate suggest that adding biologicals may help in such cases.However,certain adverse events associated with the current therapy advocate exploringnovel therapeutic approaches such as gene therapy, mesenchymal stem cell therapy in future.

Pharmacological Aspects of Natural Quercetin in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that can lead to severe joint damage, disability and mortality. Quercetin (QUE) is a natural flavonoid that is ubiquitous in fruits and vegetables. This article reviews the effect of QUE on articular and extra-articular manifestations of RA in vitro and in vivo. In general, for articular manifestations, QUE inhibited synovial membrane inflammation by reducing inflammatory cytokines and mediators, decreasing oxidative stress, inhibiting proliferation, migration and invasion, and promoting apoptosis of fibroblast-like synoviocytes (FLS), regulated autoimmune response through modulating Th17/Treg imbalance and Th17 cells differentiation, reducing autoantibodies levels and regulating ectonucleoside triphosphate diphosphohydrolase (E-NTPDase)/ectoadenosine deaminase (E-ADA) activities, reduced bony damage via lowering matrix metalloproteinase (MMP)-1, MMP-3, receptor activator of nuclear factor kappa B ligand (RANKL) expression and osteoclasts formation. For extra-articular manifestations, QUE could reverse the neurodegenerative processes of the enteric nervous system (ENS) and exhibited cytoprotective, genoprotective and hepatoprotective effects. In addition, we also summarize some contradictory experimental results and explore the possibility for these differences to form a sound basis for the clinical application of QUE for RA.

Dactylitis Is Associated With More Severe Axial Joint Damage and Higher Disease Activity in Axial Psoriatic Arthritis.

To investigate the association of dactylitis with disease activity and the severity of damage detected by radiography in patients with axial psoriatic arthritis (axPsA). Patients with axPsA who met the Classification Criteria for Psoriatic Arthritis were recruited. Clinical data, radiographic changes, and disease activity in patients with axPsA with or without dactylitis were compared using t tests, Mann-Whitney U tests, or Kruskal-Wallis tests for continuous variables. Chi-square or Fisher exact tests were used for categorical variables, and logistic regression analysis was performed to evaluate the association between dactylitis and damage detected by radiography. A total of 186 patients with axPsA were analyzed and dichotomized according to the presence or absence of dactylitis. Patients with dactylitis, as compared to those without dactylitis, had higher C-reactive protein (P = 0.004), erythrocyte sedimentation rate (P = 0.006), neutrophil-to-lymphocyte ratio (P = 0.04), and platelet-to-lymphocyte ratio (P = 0.02). In addition, patients with dactylitic axPsA, as compared to patients with nondactylitic axPsA, had higher tender joint counts, swollen joint counts, Disease Activity Index for Psoriatic Arthritis (DAPSA) scores, and Health Assessment Questionnaire scores (P < 0.001). Patients with axPsA who had dactylitis, as compared to those who did not, also had higher values for the Disease Activity Score in 28 joints, Ankylosing Spondylitis Disease Activity Score, Bath Ankylosing Spondylitis Functional Index, and Bath Ankylosing Spondylitis Disease Activity Index (P < 0.05), while fewer of these patients met the criteria for minimal disease activity and low disease activity (P < 0.05). Consistently, they had more severe damage as detected by radiography (P < 0.05), higher sacroiliac scores (odds ratio [OR] 2.08, 95% CI 1.14-3.79; P = 0.02), and a more significant reduction in bone mass density (OR 2.42, 95% CI 1.34-4.37; P = 0.003). No statistical differences were observed regarding HLA-B27 and the Leeds Enthesitis Index between these 2 groups of patients. Notably, only half of the patients with dactylitic axPsA had inflammatory back pain. Our study demonstrated that patients with axPsA who had dactylitis had higher disease activity and more severe joint damage compared to those without dactylitis. Careful examination and proper management of axial involvement are recommended.

Inhibition of Histone H3 Lysine-27 Demethylase Activity Relieves Rheumatoid Arthritis Symptoms via Repression of IL6 Transcription in Macrophages

Rheumatoid arthritis (RA) occurs in about 5 per 1,000 people and can lead to severe joint damage and disability. However, the knowledge of pathogenesis and treatment for RA remains limited. Here, we found that histone demethylase inhibitor GSK-J4 relieved collagen induced arthritis (CIA) symptom in experimental mice model, and the underlying mechanism is related to epigenetic transcriptional regulation in macrophages. The role of epigenetic regulation has been introduced in the process of macrophage polarization and the pathogenesis of inflammatory diseases. As a repressive epigenetic marker, tri-methylation of lysine 27 on histone H3 (H3K27me3) was shown to be important for transcriptional gene expression regulation. Here, we comprehensively analyzed H3K27me3 binding promoter and corresponding genes function by RNA sequencing in two differentially polarized macrophage populations. The results revealed that H3K27me3 binds on the promoter regions of multiple critical cytokine genes and suppressed their transcription, such as IL6, specifically in M-CSF derived macrophages but not GM-CSF derived counterparts. Our results may provide a new approach for the treatment of inflammatory and autoimmune disorders.

ПЕРЕКИС НЕОКИСНЕННЯ ЛІПІДІВ У СИНОВІАЛЬНІЙ РІДИНІ ХВОРИХ НА ОСТЕОАРТРИТ ПІСЛЯ SARS-CoV2-ІНФЕКЦІЇ

The 2019 coronavirus disease (Coronavirus disease 2019, COVID-19) poses a great threat to the health of people in all countries of the world. Infection with SARS-CoV-2 (Severe acute respiratory syndrome-related coronavirus 2) is a respiratory disease characterized by the development of severe life-threatening complications. COVID-19 is more likely to be severe and sometimes fatal, especially in older people with co-morbidities. A topical issue is predicting the course of chronic diseases in people who have contracted a coronavirus infection. An increasing number of cases of arthritis associated with COVID-19 have been reported in the literature, making this condition worthy of further study. It is known that the development of osteoarthritis is associated with oxidative stress and excessive production of reactive oxygen species. Lipid peroxidation products can serve as a marker of the intensity of free radical processes. The aim of the study was to determine the concentration of lipid peroxidation products in the synovial fluid of patients with osteoarthritis after SARS-CoV2 infection. All study participants were divided into two groups. The first group (n=22) is patients with osteoarthritis of knee joints II-III degree. The second group (n=14) is patients with osteoarthritis of the knee joints II-III degree, who suffered a mild and moderate form of COVID-19 6-9 months ago. In the conducted studies, the products of lipid peroxidation in the synovial fluid of patients of all research groups were evaluated.The content of diene conjugates was determined in the heptane-isopropanol extract by the spectrophotometric method, Schiff bases by the fluorimetric method. The content of TBA-active products was determined by the reaction with thiobarbituric acid (TBA). The processing of the research results was carried out using generally accepted methods of variational statistics. It was established that in the synovial fluid of patients with osteoarthritis of the knee joints who contracted COVID-19, the concentration of lipid peroxidation products increases compared to the group of patients with osteoarthritis (diene conjugates – by 1.7 times, TBА-active compounds – by 1,5 times, Schiff bases – 1.3 times). The detected changes indicate a violation of the oxidative-antioxidant balance. This indicates the prevalence of free radical processes and the development of oxidative stress directly in the joint. The results obtained by us indicate that patients with osteoarthritis may develop more severe joint damage and complications after infection with COVID-19.

Pharmacogenetics of Drug Therapies in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder that can lead to severe joint damage and is often associated with a high morbidity and disability. Disease-modifying anti-rheumatic drugs (DMARDs) are the mainstay of treatment in RA. DMARDs not only relieve the clinical signs and symptoms of RA but also inhibit the radiographic progression of disease and reduce the effects of chronic systemic inflammation. Since the introduction of biologic DMARDs in the late 1990s, the therapeutic range of options for the management of RA has significantly expanded. However, patients' response to these agents is not uniform with considerable variability in both efficacy and toxicity. There are no reliable means of predicting an individual patient's response to a given DMARD prior to initiation of therapy. In this chapter, the current published literature on the pharmacogenetics of traditional DMARDS and the newer biologic DMARDs in RA is highlighted. Pharmacogenetics may help individualize drug therapy in patients with RA by providing reliable biomarkers to predict medication toxicity and efficacy.

Peptides Bearing Multiple Post-Translational Modifications as Antigenic Targets for Severe Rheumatoid Arthritis Patients.

Rheumatoid arthritis (RA) is characterized by the presence of autoantibodies that are of paramount importance for the diagnosis and prognosis of the disease and have been implicated in its pathogenesis. Proteins resulting from post-translational modifications (PTMs) are capable of triggering autoimmune responses important for the development of RA. In this work, we investigate serum antibody reactivity in patients with an established RA against a panel of chimeric peptides derived from fibrin and filaggrin proteins and bearing from one to three PTMs (citrullination, carbamylation and acetylation) by home-designed ELISA tests (anti-AMPA autoantibodies). The role of anti-AMPAs as biomarkers linked to the presence of a more severe RA phenotype (erosive disease with radiological structural damage) and to the presence of interstitial lung disease (ILD), a severe extra-articular manifestation in RA patients entailing a high mortality, was also analyzed. In general, the association with the clinical phenotype of RA was confirmed with the different autoantibodies, and especially for IgA and IgM isotypes. The prevalence of severe joint damage was only statistically significant for the IgG isotype when working with the peptide bearing three PTMs. Furthermore, the median titers were significantly higher in patients with RA-ILD, a finding not observed for the IgG isotype when working with the single- and double-modified peptides.

Gender characteristics of gout and differences in response to taking xanthioxidase inhibitors

Introduction. To date, there is no consensus regarding the gender characteristics of the course of gout. There is little data on the possible difference between men and women in response to uric acid-lowering therapy.Aim. To compare the clinical characteristics of the course of gout and evaluate the differences in response to urate-lowering therapy (ULT) with allopurinol and febuxostat in men and women.Material and methods. The retrospective cohort study included 279 men and 83 women diagnosed with gout (ACR/EULAR, 2015). The comparative analysis of the clinical characteristics of gout, as well as responses to the intake of xanthioxidase (XO) inhibitors in representatives of different sexes, was carried out. We compared the gender characteristics of obtaining a positive response to ULT, defined as achieving a target serum uric acid (sUA) level of &lt; 360 μmol / l within 6 months of treatment, while taking allopurinol and febuxostat.Results. By the age at which the onset of gout took place, women were older than men, the duration of the disease in them was shorter. Men showed a shorter duration of the first attack of arthritis. Chronic arthritis was diagnosed in 56% of men and 35% of women (p &lt; 0.05). The process involved the joints of both the lower and upper extremities. However, more often the joints of the lower extremities were affected in men, and in the upper extremities in women. Tophus were detected in 35% of patients, of whom 30.3% were men, 4.7% were women (p &lt; 0.05). Allopurinol was prescribed to 216 men and 54 women, and febuxostat was prescribed to 63 men and 29 women. After six months, the proportion of women who achieved the target sUA was 57.5% and 65.8%, the proportion of men – 60.4% and 76.2% for allopurinol and febuxostat, respectively.Conclusion. The clinical manifestations of gout in men and women differ. Due to the pronounced increase in the level of uric acid, men develop more severe joint damage due to the tendency to chronicity. However, the study did not reveal gender differences in the response to XO inhibitors, which indicates that there is no need to choose therapy depending on the patient’s gender.

IL-38 and IL-36 Target Autophagy for Regulating Synoviocyte Proliferation, Migration, and Invasion in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease leading to severe joint damage and disability. Fibroblast-like synoviocytes (FLSs) mostly contribute to the joint inflammation and destruction in RA through distinct mechanisms. However, little is known about newly discovered interleukin- (IL-) 36 and IL-38 involving in the pathology of RA. Here, we assessed the effect of IL-36 and IL-38 on RA-FLS function using IL-36 and IL-38 overexpression plasmids. We found that IL-36 inhibited synoviocytes proliferation while IL-38 showed an opposite influence. Furthermore, IL-36 and IL-38 significantly sequestered or accelerated RA-FLS migration and invasion capacity, respectively. Mechanically, IL-36 and IL-38 targeted autophagy for RA-FLS modulation. Using autophagy inhibitor 3-MA and inducer compound rapamycin, we found that autophagy negatively regulated the survival, migration, and invasion of synovial cells. Based on these results, IL-38 in combination with autophagy inhibitor 3-MA treatment demonstrated the strongest blockage of the above three activities of RA-FLS, and IL-38 overexpression reversed rapamycin-inhibited cell proliferation, migration, and invasion. Moreover, injection of IL-36 can improve the symptoms of RA in a rat model of RA. Taken together, we conclude that IL-38 and IL-36 target autophagy for regulating synoviocyte proliferation, migration, and invasion in RA.

Comparative Analyses of Serological Biomarkers and Disease Characteristics between Elderly-onset and Younger-onset Rheumatoid Arthritis

The onset of rheumatoid arthritis (RA) may occur any time after the age of 16 years. The purpose of this study was to compare the clinical and serological differences between elderly onset RA (EORA); which is begins at the age of 60 and above, with younger onset RA (YORA). A total of 69 EORA and 82 YORA female patients were enrolled in this study. Data on medications, disease duration, age at onset, disease activity at onset and laboratory parameters were collected by reviewing the medical records. All patients had their blood samples taken for serum anticyclic citrulinated peptide (anti-CCP), IgA rheumatoid factor (RF), IgM RF and IgG RF. Besides, the subjects were assessed for their radiographic joint damage based on Modified Sharp Score (MSS) and functional disability based on the Health Assessment Questionnaire-disability Index (HAQ-DI) scores. Despite comparable disease duration and frequency of seropositivity, the YORA group had significantly higher disease activity at onset of the disease (p=0.009). In keeping with this finding, the YORA group had more severe joint damage based on radiographic assessment (MSS scores of 17.49+19.04 versus 10.04+12.79). The YORA group had significantly higher levels of IgA RF and anti-CCP with p-values of 0.035 and 0.002, respectively. Our findings suggest that YORA is associated with more severe disease, worse radiographic joint damage and higher levels of anti-CCP and IgA RF.

Destructive juvenile idiopathic arthritis: do not overlook rare genetic skeletal disorders

We read with interest the report by Takako Miyamae and colleagues describing severe joint damage, loss of carpal bones, and foreshortened fingers in a patient diagnosed with long-standing juvenile idiopathic arthritis.1 We would like to bring to the reader's attention that the reported clinical and radiographic phenotype might result from rare skeletal disorders characterised by osteolysis. Juvenile idiopathic arthritis is a group of heterogenous diseases characterised by chronic arthritis leading to severe joint damage in some individuals.

The E3 ubiquitin ligase Itch limits the progression of post-traumatic osteoarthritis in mice by inhibiting macrophage polarization

Osteoarthritis (OA) is characterized by articular cartilage loss, associated with synovial inflammation. We recently reported increased pro-inflammatory macrophages in murine post-traumatic OA (PTOA) joints, and blockade of the ubiquitin-proteasome system alleviates PTOA progression. However, the mechanisms whereby protein ubiquitination influences PTOA pathology are not well studied. We hypothesized that loss of the negative regulator of inflammation, E3 ligase Itch, in macrophages contributes to joint OA tissue damage by promoting pro-inflammatory polarization of macrophages. Mice deficient Itch in macrophages (MΔItch) were generated by crossing Itchfl/fl mice with LysM-Cre mice. PTOA surgery was performed on global Itch knockout, Itch-/-, mice and MΔItch mice. Joint tissue damage and synovial macrophages were examined. Itch-/- cells were treated with IL-1 and pro-inflammatory polarization was determined. Expression of Itch protein and mRNA in PTOA synovium were assessed at different time points post PTOA. Similar to Itch-/- mice, MΔItch mice developed more severe joint damage than control mice following PTOA surgery (mean difference of OARSI score: 1.17 (95% CI 0.31-2.03) between MΔItch and Itchfl/fl mice), accompanied by increased the inflammatory macrophage infiltration in the synovium (mean difference of % F4/80+CD86+CD36-inflammatory macrophages: 14.81 (95% CI 8.90-20.73) between MΔItch and Itchfl/fl mice). Itch-/- macrophages exerted pro-inflammatory phenotype in response to IL-1β treatment. Itch protein, but not mRNA levels decreased during PTOA progression. The negative regulator of inflammation, Itch, limits PTOA progression by inhibiting macrophage pro-inflammatory polarization. Itch protein degradation may contribute to PTOA pathology.

Activation of notch signaling in dorsal root ganglia innervating knee joints in experimental osteoarthritis

Purpose: Surgical destabilization of the medial meniscus (DMM) is a widely used mouse model of knee osteoarthritis (OA). The cell bodies of primary sensory neurons innervating the knee joints are located in the lumbar dorsal root ganglia (L3-L5 DRG). Analysis of the gene expression profile of L3-L5 DRG after DMM or sham surgery revealed that innate neuro-immune pathways were strongly regulated, especially in the later stages of the model, 8-16 weeks after DMM, when persistent pain is associated with severe joint damage.

Features of the Course and Treatment of Osteoarthritis in Patients with Osteoporosis and Obesity

The objective: features of the course and clinical manifestations of the joint syndrome and increase the effectiveness of treatment in patients with OA with osteoporosis and obesity. Materials and methods. The study included 134 patients (88 women and 46 men), aged 30 to 80 years. Depending on the body mass index, patients were divided into 2 groups: obese and normal weight. Peculiarities of the course and effectiveness of treatment were assessed using questionnaires VAS, WOMAC, Lekens. Levels of nonspecific inflammatory parameters (ESR and CRP), cytokines (IL-1, IGF-1, NO), uric acid level and bone mineral density were also studied. SPSS Statistics was used for statistical data processing. Results. The study revealed a statistically significant difference in the indicators of the questionnaires VAS, WOMAC and Leken, levels of immunological (IL-1, IGF-1, NO) and nonspecific (ESR, CRP) indicators of inflammation between the 2 groups of patients. Patients with osteoporosis and obesity had the worst questionnaires and indicators of inflammation, compared with patients with normal BMD and osteopenia. In obese patients, the dynamics of treatment was significantly worse, according to questionnaires, immunological and nonspecific indicators of inflammation. Conclusions. Patients with OA and obesity, compared with normal weight, had more severe joint damage, more intense pain, stiffness and reduced functional activity, as well as more intense inflammation. The most severe course of the disease was observed in patients with osteoporosis and obesity, compared with normal BMD and osteopenia. The dynamics of SYSADOA treatment is impaired in patients with osteoarthritis and obesity: less intense reduction of knee stiffness, pain and poorer functional activity, as well as less effective anti-inflammatory effect.

Psoriatic arthritis: the role of the nonphysician clinician in the diagnosis and treatment of patients with psoriasis

Psoriatic arthritis is a clinically heterogeneous, chronic, and progressive disease that develops in up to 30% of patients with psoriasis and is characterized by multiple and increasing joint defects caused by persistent immune-mediated inflammation. Several treatment options are available, including multiple biologic agents that inhibit specific cellular mediators of inflammation either directly or indirectly. Early detection and intervention are critical to preventing severe joint damage and pain, necessitating increased awareness and education about this disease for primary providers and nonphysician clinicians. Physician assistants and nurse practitioners, given their role in the primary care setting and within multiple specialty areas such as dermatology and rheumatology, are often the first to see patients who may have psoriatic arthritis. These healthcare providers are increasingly important in the early diagnosis and treatment of this disease. In this review, we provide an overview of psoriasis and psoriatic arthritis and discuss the multiple treatment options that are available for these patients. We also discuss ways to help recognize early joint involvement in the clinic and emphasize the role that nonphysician clinicians play in the care of patients with psoriatic arthritis.

Skin Manifestation Associated With Multicentric Reticulohistiocytosis.

Multicentric reticulohistiocytosis (MRH) is a rare multisystem disorder, primarily affecting the skin and joints. As severe joint damage is a possible symptom, early diagnosis and therapeutic intervention are required. Cutaneous lesions present with characteristic features such as discrete reddish nodules, especially on acral locations. Additionally, the face, scalp, trunk and extremities are also affected. Xanthomatous plaques are also seen on the face. The cutaneous manifestations of MRH are various, which therefore should be differentiated from several diseases. In particular, MRH has been reported to assume clinical appearances resembling Gottron papules, periungual erythema, V-neck erythema, shawl sign, and poikiloderma associated with dermatomyositis. Histopathologic features show proliferation of multinucleated giant cells with abundant eosinophilic granular ground glass-like cytoplasm in the dermis. Multicentric reticulohistiocytosis is occasionally paraneoplastic and is associated with internal malignancies. The appropriate therapies are still challenging, and oral prednisolone, immunosuppressants, and recent biologics are used. In this article, cutaneous lesions, histopathology, and pathogenesis of MRH are mainly discussed from a dermatological perspective. It is important, not only for dermatologists but also for rheumatologists and orthopedists, to be able to distinguish between the various types of skin lesions brought on by MRH. Cutaneous signs are important diagnostic clues and assessment tools for therapeutic efficacy.

Subclinical Enthesitis in Rheumatoid Arthritis Patients and its Relation to Disease Parameters and Disease Activity

Background: Rheumatoid Arthritis (RA) is a chronic systemic autoimmune disorder of unknown etiology characterized by symmetrical joint synovitis and pain. RA has a wide clinical spectrum and may vary from mild nonerosive disease to severe inflammation and joint damage with extra articular manifestations. To detect enthesopathy, the European League Against Rheumatism (EULAR) recommends magnetic resonance imaging (MRI) or ultrasonography (US). Objective: To detect subclinical enthesitis in rheumatoid arthritis patients and its relation to disease parameters and disease activity. Patients and Methods: This prospective observational study included 50 adult patients diagnosed as rheumatoid arthritis according to the 2010 ACR-EULAR classification criteria for rheumatoid arthritis. The study was carried out in the Musculoskeletal Ultrasonography Unit of the Rheumatology, Physical Medicine and Rehabilitation Department, Al-Azhar University Hospitals Assiut. Results: We found that the mean age in case group was 46.3 ± 8.4 years. Females accounted for 62% (31 patients) of all patients. The disease duration ranged from one year to 15 years with a mean of 6.2 ± 1.9 years. The BMI was 19.5 ± 42 kg/m2 . Mean of disease activity evaluated by the disease activity score in 28 joints was 4.7 ± 1.5. Our findings demonstrated that prevalence of subclinical enthesitis in patients with rheumatoid arthritis was 32%. There was a statistically significant relation between 28-joint Disease Activity Score (DAS28) score and ultrasound detected enthesitis (p. value < 0.05). Conclusion: BMI, old age and long disease duration were suggested as the risk factors for subclinical enthesitis.