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Medicina
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Recent Advances in Autoimmune Rheumatic Diseases
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Recent Advances in Autoimmune Rheumatic Diseases

A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Hematology and Immunology".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 14329

Special Issue Editors

Dr. Diana Mieliauskaitė

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Guest Editor
Department of Personalised Medicine, State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania
Interests: autoimmunity; Sjogren’s disease; non-autoimmune/autoimmune epithelitis; sicca syndrome; saliva; microbiota; personalized medicine
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Jolanta Dadonienė

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Guest Editor
1. Department of Experimental, Preventive and Clinical Medicine State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania
2. Medical Faculty, Vilnius University, Vilnius, Lithuania
Interests: epidemiology of chronic rheumatic diseases; inflammatory rheumatic diseases; vasculitis; research methodology; systematic literature reviews
Dr. Gailutė Kirdaitė

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Guest Editor
Department of Experimental, Preventive and Clinical Medicine, State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania
Interests: arthritis; biomarkers; light technologies; nanotechnologies; medical devices; regenerative medicine

Special Issue Information

Dear Colleagues,

Autoimmune rheumatic diseases are a group of diseases that share similar clinical, laboratory and immunological expression. The pathogenesis of autoimmune rheumatic diseases is not completely understood, but according to recent research studies, it is accepted that the pathogenesis of autoimmune rheumatic diseases is multifactorial. Genetic features, including certain HLA phenotypes and polymorphisms in genes that encode cytokines or factors implicated in cytokine signaling, environmental (such as infections, chemical and physical agents and lifestyle), hormonal factors, as well as stressful life events are thought to participate in autoimmune rheumatic diseases’ pathogenesis. Therefore, it is expected that people who are genetically predisposed to autoimmune rheumatic diseases can harbor gut microbiota that are capable of influencing the onset and severity of their disease. Evidence-based studies support the concept that microbiota can influence autoimmunity by molecular mimicry, epitope spreading, or bystander activation.

In the last few years, the number of individuals affected by autoimmune rheumatic diseases has increased, especially in the more economically developed countries. Autoimmune rheumatic diseases constitute a major cause of disability throughout the world, with considerable financial and social consequences on all societies.

Due to the recent progress in our understanding of the pathogenesis of autoimmune rheumatic diseases, the medical community possesses an array of effective therapeutic agents, including biologic therapies, antimetabolites and JAK inhibitors.

This Special issue is dedicated to the latest advances in autoimmune rheumatic diseases, with the hope that it will make a significant contribution to clinical practice and public health and will gather up-to-date research information on the recent advances in autoimmune rheumatic diseases. We are pleased to invite you to submit your original research, review articles and case reports to this Special Issue.

Dr. Diana Mieliauskaitė
Prof. Dr. Jolanta Dadonienė
Dr. Gailutė Kirdaitė
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Medicina is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • rheumatoid arthritis
  • systemic lupus erythematosus
  • Sjogren’s syndrome
  • systemic scleroderma
  • psoriatic arthritis
  • mixed connective tissue disease
  • ankylosing spondylitis
  • vasculitis
  • adult-onset juvenile arthritis
  • relapsing polychondritis
  • autoimmune rheumatic diseases

Related Special Issue

Published Papers (9 papers)

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Research

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9 pages, 269 KiB  
Article
Audiological Manifestations in Patients with Granulomatosis with Polyangiitis
by Vija Vainutienė, Justinas Ivaška, Jolanta Dadonienė, Vilma Beleškienė, Tatjana Ivaškienė and Eugenijus Lesinskas
Medicina 2024, 60(2), 267; https://doi.org/10.3390/medicina60020267 - 3 Feb 2024
Viewed by 840
Abstract
Background and Objectives: Granulomatosis with Polyangiitis (GPA) is a rare, autoimmune, multisystemic disease characterized by vasculitis and necrotizing granuloma that commonly affects the upper and lower respiratory tract and kidneys. Audiovestibular dysfunction in GPA diseases may have different clinical presentations. The aim [...] Read more.
Background and Objectives: Granulomatosis with Polyangiitis (GPA) is a rare, autoimmune, multisystemic disease characterized by vasculitis and necrotizing granuloma that commonly affects the upper and lower respiratory tract and kidneys. Audiovestibular dysfunction in GPA diseases may have different clinical presentations. The aim of the present study was to evaluate hearing function in patients with GPA and to compare the results with a healthy control group. Materials and Methods: A total of 34 individuals participated in the study. The GPA group consisted of 14 participants, and the control group was composed of 20 healthy participants with no signs or symptoms of ear disease. The ages ranged from 18 to 65 years old, with a mean age of 43.8 years. The participants underwent a complete audiological evaluation using otoscopy, impedance audiometry, pure tone audiometry, speech audiometry—evaluation of speech thresholds, and speech recognition in quiet. Both ears were tested. All of the participants of the study were native Lithuanian speakers. Data were statistically analyzed using the Statistical Analysis System software SAS® Studio 3.8. A p value < 0.05 was regarded as statistically significant. Results: 92.85% of patients from the GPA group reported hearing-related symptoms: hearing loss, tinnitus, and fullness in the ears. The arithmetic means of all hearing thresholds at frequencies from 125 Hz to 8000 Hz were significantly higher in the GPA group. The results revealed statistically significant differences between the two groups in the Speech Detection Threshold, Speech Recognition Threshold, Speech Discomfort level, and Word Recognition Scores. Conclusions: The frequency of hearing loss, the average hearing thresholds, and speech thresholds were higher in GPA patients than in healthy individuals. The most common type of hearing loss was sensorineural. Audiological assessments should be considered during the routine evaluation of patients with GPA disease to prevent hearing-related disabilities. Full article
(This article belongs to the Special Issue Recent Advances in Autoimmune Rheumatic Diseases)
28 pages, 18076 KiB  
Article
Amelioration of Rheumatoid Arthritis by Fragaria nubicola (Wild Strawberry) via Attenuation of Inflammatory Mediators in Sprague Dawley Rats
by Kiran Mashaal, Arham Shabbir, Muhammad Shahzad, Aisha Mobashar, Tasleem Akhtar, Tabinda Fatima, Bushra Riaz, Rana Alharbi, Afreen Fatima, Abdulkareem A. Alanezi and Ashfaq Ahmad
Medicina 2023, 59(11), 1917; https://doi.org/10.3390/medicina59111917 - 30 Oct 2023
Viewed by 1207
Abstract
Background and Objectives: Fragaria nubicola has never been evaluated scientifically for its anti-arthritic potential despite its use in folkloric systems of medicine. The research was conducted to assess the potential of F. nubicola against rheumatoid arthritis. Materials and Methods: The current study provided scientific [...] Read more.
Background and Objectives: Fragaria nubicola has never been evaluated scientifically for its anti-arthritic potential despite its use in folkloric systems of medicine. The research was conducted to assess the potential of F. nubicola against rheumatoid arthritis. Materials and Methods: The current study provided scientific evidence by evaluating the effects of plants using an in vivo CFA-induced model of arthritic rats and subsequent microscopic histopathological evaluation of ankle joints along with the determination of paw edema using a digital water displacement plethysmometer. The study also gave insight by determining levels of pro-inflammatory cytokines, matrix metalloproteinase enzymes (MMPs), prostaglandin E2 (PGE2), nuclear factor kappa B (NF-κB), vascular endothelial growth factor (VEGF), and biochemical and hematological parameters. GCMS analysis was also conducted for the identification of possible anti-inflammatory plant constituents. Results: The data showed that F. nubicola-treated groups attenuated the progression of arthritis and paw edema. Microscopic histopathological evaluation validated the anti-arthritic potential by showing amelioration of bone erosion, infiltration of inflammatory cells, and pannus formation. RT-PCR analysis displayed that treatment with F. nubicola down-regulated IL1β, IL6, TNFα, NF-κB, VEGF, MMP2, MMP3, and MMP9 levels. Moreover, ELISA exhibited a reduction in levels of PGE2 levels in treatment groups. The levels of RBCs, platelets, WBCs, and Hb content were found to be nearly similar to negative control in the treated group. Statistically, a non-significant difference was found when all groups were compared for urea, creatinine, ALT, and AST analysis, indicating the safety of plant extract and fractions at test doses. GCMS analysis of extract and fractions showed the existence of many anti-inflammatory and antioxidant phytochemicals. Conclusion: In conclusion, F. nubicola possessed anti-arthritic properties that might be attributed to the amelioration of MMPs and pro-inflammatory cytokines. Full article
(This article belongs to the Special Issue Recent Advances in Autoimmune Rheumatic Diseases)
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13 pages, 323 KiB  
Article
Association between PYTPN22 rs2476601, VEGF rs833070, TNFAIP3 rs6920220 Polymorphisms and Risk for Rheumatoid Arthritis in Early Undifferentiated Arthritis Patients: A Pilot Study
by Regina Sakalyte, Sigita Stropuviene, Gabija Jasionyte, Loreta Bagdonaite and Algirdas Venalis
Medicina 2023, 59(10), 1824; https://doi.org/10.3390/medicina59101824 - 13 Oct 2023
Viewed by 1053
Abstract
Background and Objectives: About 40% of early undifferentiated arthritis (UA) progresses to rheumatoid (RA) or other chronic arthritis. Novel diagnostic tools predicting the risk for this progression are needed to identify the patients who would benefit from early aggressive treatment. Evidence on [...] Read more.
Background and Objectives: About 40% of early undifferentiated arthritis (UA) progresses to rheumatoid (RA) or other chronic arthritis. Novel diagnostic tools predicting the risk for this progression are needed to identify the patients who would benefit from early aggressive treatment. Evidence on the role of single-nucleotide polymorphisms (SNPs) in the development of RA has emerged. The aim of our study was to investigate the association between rs2476601, rs833070, and rs6920220 SNPs and UA progression to RA. Materials and Methods: Ninety-two UA patients were observed for 12 months. At study entry, demographic and clinical characteristics were recorded, musculoskeletal ultrasonography was performed, and blood samples were drawn to investigate levels of inflammatory markers, rheumatoid factor (RF), anti-citrullinated protein antibodies (anti-CCP)detect SNPs. After 12 months, UA outcomes were assessed, and patients were divided into two (RA and non-RA) groups. The association between the risk of progression to chronic inflammatory arthritis and analyzed SNPs was measured by computing odds ratios (OR). Results: After a 12-month follow-up, 27 (29.3%) patients developed RA, and 65 (70.7%) patients were assigned to the non-RA group. The arthritis of 21 patients (22.8%) from the non-RA group resolved completely, while the other 44 (47.2%) patients were diagnosed with another rheumatic inflammatory disease. The patients who developed RA had a significantly greater number of tender and swollen joints (p = 0.010 and p = 0.021 respectively) and were more frequently RF or anti-CCP (p < 0.001), and both RF and anti-CCP positive (p < 0.001) at the baseline as compared with the patients in the non-RA group. No significant association between rs2476601 (OR = 0.99, p = 0.98), rs833070 (OR = 1.0, p = 0.97), and rs6920220 (OR = 0.48, p = 0.13) polymorphisms and the risk of developing RA were found. Conclusions: No association between analyzed SNPs and a greater risk to progress from UA to RA was confirmed, although patients with rs6920220 AA + AG genotypes had fewer tender joints at the disease onset. Full article
(This article belongs to the Special Issue Recent Advances in Autoimmune Rheumatic Diseases)

Review

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11 pages, 741 KiB  
Review
Insights into Microbiota in Sjögren’s Syndrome
by Diana Mieliauskaitė and Vilius Kontenis
Medicina 2023, 59(9), 1661; https://doi.org/10.3390/medicina59091661 - 14 Sep 2023
Viewed by 1154
Abstract
Primary Sjögren’s syndrome (pSS) is a heterogeneous chronic autoimmune disorder with multiple clinical manifestations that can develop into non-Hodgkin’s lymphoma in mucosa-associated lymphoid tissue. The pathogenesis of Sjögren’s syndrome (SS) is not completely understood, but it is assumed that pathogenesis of SS is [...] Read more.
Primary Sjögren’s syndrome (pSS) is a heterogeneous chronic autoimmune disorder with multiple clinical manifestations that can develop into non-Hodgkin’s lymphoma in mucosa-associated lymphoid tissue. The pathogenesis of Sjögren’s syndrome (SS) is not completely understood, but it is assumed that pathogenesis of SS is multifactorial. The microbiota plays a notable role in the development of autoimmune disorders, including Sjögren’s syndrome. Molecular mimicry, metabolite changes and epithelial tolerance breakdown are pathways that might help to clarify the potential contribution of the microbiota to SS pathogenesis. This review aims to provide an overview of recent studies describing microbiota changes and microbiota mechanisms associated with Sjögren’s syndrome. Data on the microbiota in SS from PubMed, Web of Science, Scopus and the Cochrane Library databases are summarized. Overall, the microbiota makes a major contribution to the development of Sjögren’s syndrome and progression. Future microbiota studies should improve the management of this heterogeneous autoimmune disease. Full article
(This article belongs to the Special Issue Recent Advances in Autoimmune Rheumatic Diseases)
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15 pages, 1013 KiB  
Review
The Immunomodulatory Role of Microbiota in Rheumatic Heart Disease: What Do We Know and What Can We Learn from Other Rheumatic Diseases?
by Amira Kohil, Wafa Abdalla, Wisam N. Ibrahim, Khalid M. Al-Harbi, Amal Al-Haidose, Maha Al-Asmakh and Atiyeh M. Abdallah
Medicina 2023, 59(9), 1629; https://doi.org/10.3390/medicina59091629 - 8 Sep 2023
Viewed by 1779
Abstract
Rheumatic heart disease (RHD) represents a serious cardiac sequela of acute rheumatic fever, occurring in 30–45% of patients. RHD is multifactorial, with a strong familial predisposition and known environmental risk factors that drive loss of immunological tolerance. The gut and oral microbiome have [...] Read more.
Rheumatic heart disease (RHD) represents a serious cardiac sequela of acute rheumatic fever, occurring in 30–45% of patients. RHD is multifactorial, with a strong familial predisposition and known environmental risk factors that drive loss of immunological tolerance. The gut and oral microbiome have recently been implicated in the pathogenesis of RHD. Disruption of the delicate balance of the microbiome, or dysbiosis, is thought to lead to autoimmune responses through several different mechanisms including molecular mimicry, epitope spreading, and bystander activation. However, data on the microbiomes of RHD patients are scarce. Therefore, in this comprehensive review, we explore the various dimensions of the intricate relationship between the microbiome and the immune system in RHD and other rheumatic diseases to explore the potential effect of microbiota on RHD and opportunities for diagnosis and treatment. Full article
(This article belongs to the Special Issue Recent Advances in Autoimmune Rheumatic Diseases)
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13 pages, 1095 KiB  
Review
Disentangling the Pathogenesis of Systemic Lupus Erythematosus: Close Ties between Immunological, Genetic and Environmental Factors
by Henry Sutanto and Yuliasih Yuliasih
Medicina 2023, 59(6), 1033; https://doi.org/10.3390/medicina59061033 - 26 May 2023
Cited by 9 | Viewed by 3437
Abstract
Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease that attacks various organ systems with a variety of clinical implications, ranging from mild skin and mucosal manifestations to severe central nervous system manifestations and death. Cases of SLE have been documented nearly two [...] Read more.
Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease that attacks various organ systems with a variety of clinical implications, ranging from mild skin and mucosal manifestations to severe central nervous system manifestations and death. Cases of SLE have been documented nearly two centuries ago when scholars used the terms ‘erythema centrifugum’ and ‘seborrhea congestiva’ to describe the discoid skin lesions and the butterfly or malar rash in SLE. Since then, knowledge about this disease has developed rapidly, especially knowledge related to the underlying pathogenesis of SLE. To date, it is known that immune system dysregulation, supported by genetic and environmental predisposition, can trigger the occurrence of SLE in a group of susceptible individuals. Various inflammatory mediators, cytokines and chemokines, as well as intra- and intercellular signaling pathways, are involved in the pathogenesis of SLE. In this review, we will discuss the molecular and cellular aspects of SLE pathogenesis, with a focus on how the immune system, genetics and the environment interact and trigger the various clinical manifestations of SLE. Full article
(This article belongs to the Special Issue Recent Advances in Autoimmune Rheumatic Diseases)
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Other

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9 pages, 7392 KiB  
Case Report
Overlapping Case of Advanced Systemic Sclerosis and IgG4-Related Disease after Autologous Hematopoietic Stem Cell Transplantation
by Alisa Julija Dulko, Irena Butrimiene, Alma Cypiene, Valdas Peceliunas, Donatas Petroska, Ernesta Stankeviciene and Rita Rugiene
Medicina 2024, 60(3), 496; https://doi.org/10.3390/medicina60030496 - 18 Mar 2024
Viewed by 808
Abstract
Both scleroderma and immunoglobulin G4-related disease (IgG4-RD) are systemic fibro-inflammatory diseases characterised by lymphoplasmacytic infiltrates. IgG4-RD and systemic sclerosis (SSc) may share common pathophysiological mechanisms, but no examples of co-occurrence of the diseases have been found. Autologous haematopoietic stem cell transplantation (AHSCT) is [...] Read more.
Both scleroderma and immunoglobulin G4-related disease (IgG4-RD) are systemic fibro-inflammatory diseases characterised by lymphoplasmacytic infiltrates. IgG4-RD and systemic sclerosis (SSc) may share common pathophysiological mechanisms, but no examples of co-occurrence of the diseases have been found. Autologous haematopoietic stem cell transplantation (AHSCT) is implemented in selected rapidly progressive SSc with a high risk of organ failure. However, existing guidelines are based on clinical trials that do not represent the entire patient population and exclude critically ill patients with no therapeutic alternatives. Examples of AHSCT in IgG4-RD are absent. We report the case of a 44-year-old female patient with overlapping progressive diffuse SSc and sinonasal IgG4-RD. After 11 years of ineffective SSc treatment, AHSCT was performed. The 63-month follow-up showed a regression of SSc symptoms. AHSCT was not intended as treatment in the case of IgG4RD, although the first symptoms of the disease developed before transplantation. The sinus lesions progressed after AHSCT and remained indolent only after surgical treatment (bilateral ethmoidectomy, sphenoidotomy, intranasal buccal antrostomy), which allowed histopathological confirmation of IgG4-RD. Full article
(This article belongs to the Special Issue Recent Advances in Autoimmune Rheumatic Diseases)
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8 pages, 917 KiB  
Case Report
Successful Treatment of a Patient with Drug-Refractory Rheumatoid Arthritis-Associated Interstitial Lung Disease with Upadacitinib: A Case Report
by Yuuya Nishii, Masaki Okamoto, Yoshiaki Zaizen, Takashi Kojima, Takashi Nouno, Yoshiko Naitou-Nishida, Norikazu Matsuo, Hiroaki Takeoka, Motoko Ishida, Masataka Nakamura, Toru Masuda, Takafumi Tanaka, Tomoya Miyamura and Tomoaki Hoshino
Medicina 2023, 59(11), 1960; https://doi.org/10.3390/medicina59111960 - 6 Nov 2023
Cited by 1 | Viewed by 1589
Abstract
Insufficient evidence exists regarding the efficacy of Janus kinase inhibitors (JAKis), a class of targeted synthetic disease-modifying anti-rheumatic drugs (tsDMARDs), in the treatment of rheumatoid arthritis (RA)-associated interstitial lung disease (ILD). Herein, we present a case of RA-ILD refractory to previous treatments that [...] Read more.
Insufficient evidence exists regarding the efficacy of Janus kinase inhibitors (JAKis), a class of targeted synthetic disease-modifying anti-rheumatic drugs (tsDMARDs), in the treatment of rheumatoid arthritis (RA)-associated interstitial lung disease (ILD). Herein, we present a case of RA-ILD refractory to previous treatments that exhibited favorable response to upadacitinib. A 69-year-old man, former smoker, was diagnosed with RA-ILD based on persistent symmetric polyarthritis, elevated C-reactive protein levels and erythrocyte sedimentation rate, reduced diffusing capacity for carbon monoxide/alveolar volume (DLCO 69.9%), and bilateral ground-glass attenuation with traction bronchiectasis, predominantly in the lower lung lobe. Initial treatment with oral prednisolone and methotrexate was started; however, the patient showed worsening dyspnea, chest high-resolution computed tomography abnormalities, and decreased pulmonary function. The dose of prednisolone was increased, and methotrexate was shifted to tacrolimus; however, tacrolimus was eventually discontinued because of renal dysfunction. Subsequent treatment changes included abatacept followed by intravenous cyclophosphamide, but ILD activity continued to worsen and met the criteria of progressive pulmonary fibrosis. Approximately 4.5 years after the RA diagnosis, dyspnea, radiological abnormalities, and DLCO improved following treatment switch to upadacitinib, one of JAKis. JAKi therapy may have potential as a treatment option for refractory RA-ILD. Full article
(This article belongs to the Special Issue Recent Advances in Autoimmune Rheumatic Diseases)
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11 pages, 612 KiB  
Systematic Review
The Use of Superb Microvascular Imaging in Evaluating Rheumatic Diseases: A Systematic Review
by Goda Seskute, Gabija Jasionyte, Rita Rugiene and Irena Butrimiene
Medicina 2023, 59(9), 1641; https://doi.org/10.3390/medicina59091641 - 11 Sep 2023
Cited by 1 | Viewed by 1799
Abstract
Background and Objectives: Superb microvascular imaging is an advanced Doppler algorithm that seems to be useful in detecting low-velocity blood flow without using a contrast agent. Increasing evidence suggests that SMI is a more sensitive tool than conventional Doppler techniques for evaluating [...] Read more.
Background and Objectives: Superb microvascular imaging is an advanced Doppler algorithm that seems to be useful in detecting low-velocity blood flow without using a contrast agent. Increasing evidence suggests that SMI is a more sensitive tool than conventional Doppler techniques for evaluating rheumatic diseases, especially inflammatory arthritis. We aimed to assess the use of SMI in evaluating joints and extraarticular structures. Materials and Methods: Two reviewers independently reviewed the literature to provide a global overview of the possibilities of SMI in rheumatology. Original English-language articles published between February 2014 and November 2022 were identified through database (PubMed, Medline, Ebsco, the Cochrane Library, and ScienceDirect) searching, and analysed to summarise existing evidence according to PRISMA methodology. Inclusion criteria covered original research articles reporting applications of SMI on rheumatic diseases and musculoskeletal disorders secondary to rheumatic conditions. Qualitative data synthesis was performed. Results: A total of 18 articles were included. No systematic reviews fulfilled our inclusion criteria. Most studies focused on characterising the synovial vascularity of rheumatoid arthritis. There have been several attempts to demonstrate SMI’s value for evaluating extra-articular soft tissues (fat pads or salivary glands) and large-diameter vessels. The quantitative importance of SMI vascular indices could become a useful non-invasive diagnostic marker. Studies on therapeutic applications are still scarce, and the majority of studies have gaps in reporting the methodology (ultrasound performance technique and settings) of the research. Conclusions: SMI has proved to be useful in characterising low-flow vascularity, and growing evidence indicates that SMI is a non-invasive and lower-cost tool for prognostic assessment, especially in inflammatory arthritis. Preliminary findings also suggest potential interest in evaluating the effect of treatment. Full article
(This article belongs to the Special Issue Recent Advances in Autoimmune Rheumatic Diseases)
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