Current Rheumatology Reviews - Volume 19, Issue 4, 2023

Background: A microsponge delivery system (MDS) is a cutting-edge and distinctive method of structured medication delivery. Regulated drug distribution is now possible with the use of microsponge technology. Techniques for drug release are created specifically to distribute medications to the body's various locations. As a result, pharmacological therapy becomes more effective, and patient compliance significantly affects the health care system. Main Body: MDS consists of porous microspheres with a substantially porous structure and a very small spherical shape, ranging in size from 5 to 300 microns. MDS is typically used to administer medications through topical channels, but new research has demonstrated the promise of this technique for parenteral, oral, and ocular drug delivery. Topical formulations are an attempt to manage diseases like osteoarthritis, rheumatoid arthritis, psoriasis, etc. While reducing the drug's side effects, MDS can readily change the pharmaceutical release shape and enhance formulation stability. Reaching the highest peak plasma concentration in the blood is the main goal of microsponge medication delivery. The ability of MDS to self-sterilize is by far the most notable quality. Conclusion: In countless studies, MDS is employed as an anti-allergic, anti-mutagenic, and nonirritant. This review covers the overview of microsponges along with their release mechanism. The article focuses on the marketed formulation of microsponges and patent data of the same. This review will be helpful for researchers working in MDS technology.

Introduction: Rheumatic diseases are a spectrum of autoimmune or inflammatory diseases that cause damage to the musculoskeletal system as well as vital organs, such as the heart, lungs, kidneys, and central nervous system. Methods: The study of rheumatic disease has made great progress in the understanding and management of these conditions in the last few decades using disease-modifying antirheumatic drugs and synthesized biological immunomodulating therapies. However, one potential treatment that has not been well investigated in rheumatic disease is platelet-rich plasma (PRP). PRP is proposed to facilitate the healing of injured tendons and ligaments through a variety of mechanisms, including mitogenesis, angiogenesis and macrophage activation via cytokine release, although its exact mechanism is unclear. Result: There has been a great deal of work in determining the exact preparation method and composition of PRP for regenerative purposes in orthopedic surgery, sports medicine, dentistry, cardiac surgery, pediatric surgery, gynecology, urology, plastic surgery, ophthalmology, and dermatology. Despite this, there is a paucity of research on the impact of PRP on rheumatic disease. Conclusion: This study aims to summarize and evaluate the current research concerning the use of PRP in rheumatic disease.

Rheumatoid arthritis (RA) is a chronic disease characterized by joint and systemic involvement that develops with different pathogenetic mechanisms. Treatment of the disease is undertaken with disease-modifying anti-rheumatic drugs (DMARDs). The mechanisms of action of conventional DMARDs generally are based on the inhibition of T and B-cells in the immune system. In recent years, biologic and targeted smart molecules have been used in the treatment of RA. Targeting different cytokines and inflammatory pathways, these drugs have ushered in a new era in RA treatment. The efficacy of these drugs has been demonstrated in many studies; and in the postmarketing period, that is, as the patients who use them say, they are like a “stairway to heaven”. However, as every "road to heaven” is challenging and “thorny”, the efficacy and reliability of these drugs and whether any one of them is superior to the others, remains a matter of debate. However, the use of biologic drugs with or without cDMARDs, the preference for original vs. biosimilar molecules, and discontinuation of the drugs after achieving sustained remission are other questions that need to be explored. When it comes to the choice of biological drugs by rheumatologists, it is not yet clear on which criteria they base their choices on. Due to the limited comparative studies of these biological drugs, the subjective criteria of the physician gains importance. The selection of these drugs, however, should be based on objective criteria such as efficacy, safety, superiority over each other, and cost. In other words, the determinant of the "path to heaven" should be based on objective criteria and recommendations according to the scientific data generated by controlledprospective studies, not on the initiative of a single physician. In this review, a head-to-head comparison of biological drugs used in the treatment of RA, their efficacy, safety, and which are superior are discussed in light of recent literature data.

Introduction: Reactive arthritis (ReA) is a joint inflammation that follows an infection at a distant site, often in the gastrointestinal or urogenital tract. Since the emergence of COVID-19 in January 2020, several case reports have suggested a relation between reactive arthritis and severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), due to the novelty of the disease, most findings were reported in the form of case reports or case series, and a comprehensive overview is still lacking. Methods: We searched PubMed/Medline and Embase to identify studies addressing the association between ReA and COVID-19. The following terms were used: (“Reactive Arthritis” OR “Post-Infectious Arthritis” OR “Post Infectious Arthritis”) AND (“COVID-19” OR “SARS-CoV-2” OR “2019-nCoV”). Results: A total number of 35 reports published up to February 16^th, 2022, were included in this study. A wide range of ages was affected (mean 41.0, min 4 max 78), with a higher prevalence of males (61.0%) from 16 countries. The number and location of the affected joints were different in included patients, with a higher prevalence of polyarthritis in 41.5% of all cases. Cutaneous manifestations and visual impairments were found as the most common associated symptoms. Most patients (95.1%) recovered, with a mean recovery time of 24 days. Moreover, arthritis induced by COVID-19 seems to relieve faster than ReA, followed by other infections. Conclusion: ReA can be a possible sequel of COVID-19 infection. Since musculoskeletal pain is a frequent symptom of COVID-19, ReA with rapid onset can easily be misdiagnosed. Therefore, clinicians should consider ReA a vital differential diagnosis in patients with post-COVID-19 joint swelling. Additional studies are required for further analysis and to corroborate these findings.

Background: Carpal tunnel syndrome (CTS) is a debilitating neuropathy that accompanies pain and other physical limitations and disrupts the normal functioning of the victims' lives. Objective: We aimed to investigate Vitamin D's preventive and therapeutic effects on the occurrence and remission of CTS symptoms. Methods: In this systematic review the PRISMA statement has been designed primarily. An extensive search was undertaken in various databases, including PubMed, Cochrane library, Web of Science, EMBASE, and Scopus. After considering the inclusion and exclusion criteria of the study, finally, 19 articles were retrieved. The raw data were extracted and entered into an Excel form, and the study outcomes were investigated. Results: The main symptoms and tests, including functional score, nerve conduction, and pain, were improved after Vitamin D supplementation in CTS patients. However, they revealed worse scores in people with low Vitamin D levels. In addition, the scores of mentioned indices were worsened in people with lower serum Vitamin D levels. Nevertheless, some studies did not find a significant relationship between low serum 25(OH)D and more significant pain scores in CTS patients. In addition, Vitamin D inserts its effects on CTS by regulating cell proliferation, nerve growth factor, suppression of oxidative stress and inflammatory cytokines, and improvement in cartilage and microvascular damage. Conclusion: Vitamin D supplementation can improve the symptoms in CTS patients, and low serum 25(OH)D can aggravate the symptoms of the disease and could be a risk factor for its occurrence. However, more observational studies and clinical trials are needed.

Background: Axial spondyloarthritis (axSpA) may lead to functional and physical disturbances. Self-administered questionnaires can measure functional limitations associated to axSpA. If these questionnaires are currently used in clinical practice and research, the French version of these questionnaires has not been validated. The aim of this study was to translate and perform a linguistic validation of the Bath Ankylosing Spondylitis Functional Index (BASFI) and the Bath Ankylosing Spondylitis Global score (BAS-G) in French. Methods: The study has been approved by local ethic committee and is registered in Clinical Trial (NCT04212806). The translation process was performed through a forward/backward validation process, followed by clinician experts validation and patient cognitive interviews. Results: The two questionnaires were translated into a French version by two independent translators. Translators then agreed on sentences being different between the two translations. The backward translation was equivalent to the initial English version except for two questions. Five French clinician experts on rheumatology made essential changes in sentences constructions of the translated questionnaire. The last version of the questionnaires was presented to 5 patients with axSpA which all found them clear and understandable. Conclusion: BASFI and BAS-G would be a generally reliable instrument for patients with axSpA. These questionnaires can be widely used in clinical practice and research in French-speaking population. The use of these questionnaires is expected to have a positive impact on patient care to better understand physical consequences of axSpA.

Background: Polymyositis (PM) and dermatomyositis (DM) are non-suppurative and autoimmune inflammatory diseases of striated muscle. Interstitial lung disease (ILD) is a group of heterogeneous diseases that mainly involve the pulmonary interstitium, alveoli, and/or bronchioles, also known as diffuse parenchymal lung disease (DPLD). A significant cause of death in persons with polymyositis (PM) and dermatomyositis (DM) is concurrent interstitial lung disease (ILD). However, research on the clinical characteristics and associated influencing factors of PM/DM combined with ILD (PM/DM-ILD) is currently scarce in China. Objective: The study aimed to probe the clinical features and risk factors of PM/DM-ILD. Methods: The data of 130 patients with PM/DM were gathered. General medical status, clinical symptoms, laboratory parameters, high-resolution CT, therapeutic outcomes, and prognoses were retrospectively reviewed in patients with PM/DM with (ILD group) and without (NILD) ILD. Results: The age of the ILD group (n=65) was more than the NILD group (n=65), and the difference was statistically significant; there were no significant between-group variations in the PM/DM ratio, sex, or duration of the disease. The initial symptoms were arthritis and respiratory symptoms in the ILD group, and myasthenia symptoms in the NILD group. Incidences of Raynaud’s phenomenon, dry cough, expectoration, dyspnea on exertion, arthritis, fever, total globulin (GLOB), erythrocyte sedimentation rate (ESR), and anti-Jo-1 antibody rate were higher for ILD; however, albumin (ALB), creatine kinase aspartate aminotransferase activity ratio (CK/AST) and CK levels were significantly lower in the ILD group. Bivariate logistic regression analysis showed age, dry cough, arthritis, dyspnea on exertion, anti-Jo-1 antibody, and elevated GLOB to be independent risk factors for ILD among patients with PM/DM. Conclusion: Advanced age, dry cough, arthritis, dyspnea on exertion, anti-Jo-1 antibody positivity, and elevated GLOB level are risk factors for PM/DM-ILD. This information could be utilized to carefully monitor changing lung function in these patients.

Objective: One of the potential factors that cause systemic lupus erythematosus (SLE) development is autophagy. Immunity-related GTPase family M protein (IRGM) has been shown to be linked to immune-mediated diseases. The aim of the current study was to assess the role of the IRGM-autophagy gene in SLE susceptibility in an Egyptian population and its relation to lupus nephritis. Methods: A case-control study was conducted in which a total of 200 subjects (100SLE and 100 healthy controls) were enrolled. Two single-nucleotide polymorphisms (SNPs) (rs10065172 and rs4958847) were genotyped. Genotypes and alleles analysis was conducted to compare between cases and controls, as well as a stratification analysis was conducted on the presence or absence of lupus nephritis. Results: Among selected SNPs of IRGM, no association was found between both SNPs and SLE susceptibility. For rs10065172, the major expressed genotype was CC (61% and 71%) (Adj OR= 2.9, 95%= 0.545-15.5), followed by TC (34% and 27%) (Adj OR= 1.985, 95% = 0.357-11.041) in cases and controls, respectively. For rs4958847, AA and AG were comparably expressed in case [(43% and 39%) (Adj OR= 1.073, 95% = 0.483-2.382)] and control [(41% and 43%) (Adj OR= 1.24, 95% = 0.557- 2.763)], respectively. Additionally, no relationship among both SNPs and gender, lupus nephritis, disease activity, or disease duration, was observed. Conclusion: IRGM SNPs (rs10065172 and rs4958847) expression was comparable among SLE patients and controls of the Egyptian cohort. Genotype and allele frequency of IRGM SNPs did not differ in lupus nephritis and non-lupus nephritis patients.

Background: Psoriatic arthritis (PsA) is a musculoskeletal disease that adversely affects physical mobility and quality of life. It is challenging to manage because of the heterogeneous nature of the symptoms and the current treatment options. Purpose: To explore the patient and rheumatologist perspectives of PsA to help improve understanding of the disease experience and improve disease management. Methods: A descriptive, observational cross-sectional study of Saudi Arabian dermatologists and rheumatologists and patients with psoriasis or PsA was conducted. Questionnaire data were collected from 31 dermatologists, 34 rheumatologists, 90 patients with psoriasis, and 98 patients with PsA and analysed using descriptive statistics. Here, data from rheumatologists and patients with PsA are presented. Results: The results revealed similarities and differences in the rheumatologist and patient perspectives of PsA. Rheumatologists and patients agreed on the impact that PsA had on patients’ quality of life and that more education was needed. However, they differed on several aspects of disease management. Rheumatologists estimated the time to diagnosis as four times shorter than what patients experienced. Patients accepted their diagnosis more than rheumatologists perceived them to; rheumatologists perceived patients to be worried or fearful. Patients perceived joint pain as their most severe symptom, in contrast to rheumatologists, who presumed skin appearance was the most severe symptom. Reported input into PsA treatment goals differed significantly. More than half of the rheumatologists reported equal patient-physician input into goal development as opposed to <10% of patients reporting the same. Almost half of patients reported no input into the development of their treatment goals. Conclusion: The management of PsA could benefit from enhanced screening and re-evaluation of what PsA outcomes have the most value to patients and rheumatologists. A multidisciplinary approach is recommended with increased patient involvement in disease management and individualized treatment options.

Objective: To assess central sensitization in young patients with spondyloarthritis (SpA) and to study the associated factors with higher central sensitization scores. Methods: This was a cross-sectional study including patients with SpA (ASAS criteria) aged less than 50 years. For all patients, we collected the sociodemographic and disease characteristics data. Central sensitization was assessed using a validated tool: The Central Sensitization inventory (CSI). Pain status, fibromyalgia, quality of life, anxiety and depression were screened by the Brief pain inventory, the Fibromyalgia rapid screening tool (FiRST), the ASQoL, and the Hospital anxiety and depression scale (HAD) anxiety and depression. Univariable and multivariable linear regression analyses were performed to achieve our objective. Results: Seventy-two patients were enrolled (65,2% males). The median age was 39 (28,25-46) years. Median BASDAI and ASDAS-CRP scores were 3 (2.1 - 4.7) and 2.7 (1.9 - 3.48), respectively. The median value of the CSI score was 15 (6,25-33,75); a CSI≥40 was noted in 15.3% of patients. Depression, anxiety scores, fibromyalgia and impaired QoL were screened in 11%, 9,7%, 9,7%, and 44,4%, respectively. CSI≥40 was positively correlated with ASQoL, FiRST, HAD anxiety, HAD depression and the 5 categories of pain interference (mood, regular work, relationships, sleep and enjoyment of life). Multivariate analysis identified a predictive model which included the combination of FiRST, BASDAI and ASQoL. First was the strongest predictive factor of a higher central sensitization. Conclusion: CS is frequent among SpA patients and should be looked for in order to improve QoL.

Objective: The purpose of this study was to assess the performance of computed tomography (CT) scan and magnetic resonance imaging (MRI) for detecting sacroiliitis in nonradiographic SpA (nr-SpA). Methods: This cross-sectional monocentric double-blind study included 63 patients consulting for symptoms suggestive of SpA between February 2014 and February 2017. Patients with conventional radiographs showing a confirmed sacroiliitis (grade 3 or 4) were not included. Eligible patients underwent CT and MRI of sacroiliac joints (SIJ). CT and MR images were interpreted by 2 experienced musculoskeletal radiologists blinded to clinical and laboratory data. Two professors in rheumatology blinded to radiologists’ conclusions analyzed clinical data, laboratory tests, HLA typing, X-rays, CT and MRI images, and divided the patients into 2 groups: confirmed nr-SpA or no SpA. This classification was considered the gold standard when analyzing the results. Results: 46 women and 17 men were included in this study. 47 patients were classified as confirmed nr-SpA (74.6%) and 16 patients as no SpA (25.4%). Sensitivity, specificity, and positive and negative predictive values of CT and MRI for detecting sacroiliitis were, respectively, estimated at 71.7%, 71.4%, 89.2%, 43.5%, and 51.2%, 100%, 100%, and 40%. CT and MRI findings were found to be statistically associated (p<0.001). Conclusion: SIJ MRI is a highly specific method in the detection of sacroiliitis, but with a moderate sensitivity. SIJ CT scan, usually known as the third option after radiography and MRI, has much greater diagnostic utility than it has been documented previously.

Objective: This study was conducted to determine the association between gastroesophageal reflux disease (GERD) and rheumatoid arthritis (RA) by pooling the evidence from all available studies. Methods: Potentially eligible studies were identified from MEDLINE and EMBASE database from inception to April 2021 employing a search strategy that consisted of terms for “Rheumatoid Arthritis” and “Gastroesophageal Reflux Disease”. Eligible studies for the meta-analysis were recruited with conditions of being cohort studies that included rheumatoid arthritis and without rheumatoid arthritis individuals. Together with this, prevalence of GERD in both groups and the odds ratio (OR) comparing the prevalence of GERD between the two cohorts have been reported. The retrieved point estimates with standard errors from each study were pooled into the final result by the random-effect model and generic inverse variance method as described by DerSimonian and Laird. Results: A total of 3,646 articles were identified. After two rounds of independent review by two investigators, five cohort studies were included in the meta-analysis as they met the eligibility criteria. The pooled analysis demonstrated a significant association between RA and GERD with the pooled odds ratio of 1.98 (95% CI, 1.49 - 2.65). High statistical heterogeneity with I2 of 83% was observed. The funnel plot was symmetric and publication bias was not observed. Conclusion: This systematic review and meta-analysis found a significant association between GERD and RA.

Introduction: Juvenile dermatomyositis (JDM), a rare multisystemic autoimmune disease of unknown cause, leads to chronic inflammation of both striated and smooth muscles. SARS - Co V2 virus infection in children generally remain asymptomatic. However, in some children it leads to a detailed immunological response named as multisystem inflammatory syndrome in children (MIS-C). Post recovery, occasionally, children are susceptible to other autoimmune disorders. Case Presentation: Our case post MIS-C developed JDM. 8-year-old malnourished child developed proximal myopathy of both upper and lower limbs post recovery from COVID 19. His disease severity increased within a short span of time and he went on to develop contractures and deformity of both upper and lower limbs. He developed an uncommon complication of JDM in form of highgrade non-Hodgkin’s lymphoma. Conclusion: This case highlights the importance of long-term complications of COVID-19 in children which would gradually evolve in the next few years.

Introduction: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease with variable clinical presentation, including neuropsychiatric manifestations. It has a different diagnostic approach and several different therapeutic options. Case Report: We describe a case of a young woman who first presented with arthritis, serositis, and pancreatitis, and was treated with mycophenolate mofetil initially. The patient presented with neurological symptoms suggestive of neuropsychiatric manifestations three weeks later, confirmed by Brain Magnetic Resonance Imaging (MRI). The treatment was changed to cyclophosphamide; however, the day after the infusion, she developed status epilepticus and was admitted to the intensive care unit. Repeated brain MRI revealed Posterior Reversible Encephalopathy Syndrome (PRES). Cyclophosphamide was discontinued and rituximab was initiated. The patient’s neurological manifestations improved, and she was discharged after 25 days of use. Conclusion: Immunosuppressive agents, such as cyclophosphamide have been described as a potential risk factor for PRES; however, it is not clear from the available literature whether cyclophosphamide therapy is just a marker of more severe SLE or a true risk factor for PRES.