Recent Advances in Diagnosis and Treatment in Rheumatology

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: closed (31 October 2024) | Viewed by 13245

Special Issue Editors


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Guest Editor
Unit of Rheumatology, Department of Medicine, University of Padova, Padova, Italy
Interests: rheumatology; biomarkers; systemic lupus erythematosus; idiopathic inflammatory myopathies; rheumatoid arthritis

E-Mail Website
Guest Editor
Unit of Rheumatology, Department of Medicine, University of Padova, Padova, Italy
Interests: rheumatology; biomarkers; polyangiitis

Special Issue Information

Dear Colleagues,

Rheumatology is a young branch of medicine, comprising about two hundred diseases, usually classified into three major groups: inflammatory osteoarticular diseases, systemic autoimmune diseases, and non-inflammatory musculoskeletal diseases, i.e., osteoarthritis and osteoporosis.

The present Special Issue entitled “Recent Advances in Diagnosis and Treatment in Rheumatology” will cover the best clinical, biological, and translational insights in the field of autoimmunity and rheumatology. Special focus will be devoted to rare and complex rheumatological diseases. About 50% of rare diseases are rheumatological. Advances of research in autoimmunity, connective tissue diseases’ pathogenesis and outcomes, and personalized medicine approaches to diagnosis, prognosis, and treatment will be presented. 

This Special Issue will focus but is not restricted to the following topics:

  • Novel treatment strategies for rheumatoid arthritis and spondiloarthritis;
  • Challenges in the diagnosis and treatment of lung involvement in connective tissue diseases;
  • Idiopathic inflammatory myopathies;
  • Treatment of systemic vasculitis;
  • Novel diagnostic biomarkers of systemic autoimmune diseases. 

Prof. Dr. Anna Ghirardello
Prof. Dr. Roberto Padoan
Guest Editors

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Keywords

  • rheumatology
  • systemic autoimmune diseases
  • osteoarthritis
  • systemic vasculitis
  • idiopathic inflammatory myopathies
  • rheumatoid arthritis
  • spondyloarthritis
  • biomarkers

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Published Papers (8 papers)

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10 pages, 242 KiB  
Article
Comparison of Lineblot and Immunoprecipitation Methods in the Detection of Myositis-Specific and Myositis-Associated Antibodies in Patients with Idiopathic Inflammatory Myopathies: Consistency with Clinical Diagnoses
by Fabrizio Angeli, Eleonora Pedretti, Emirena Garrafa, Micaela Fredi, Angela Ceribelli, Franco Franceschini and Ilaria Cavazzana
Diagnostics 2024, 14(19), 2192; https://doi.org/10.3390/diagnostics14192192 - 30 Sep 2024
Viewed by 500
Abstract
Background: the reference method for detection of myositis-specific and myositis-associated antibodies (MSAs and MAAs) is considered immunoprecipitation (IP), but it is routinely replaced by semi-automated methods, like lineblot (LB). Few data are available on the consistency with clinical diagnoses; thus, we aim at [...] Read more.
Background: the reference method for detection of myositis-specific and myositis-associated antibodies (MSAs and MAAs) is considered immunoprecipitation (IP), but it is routinely replaced by semi-automated methods, like lineblot (LB). Few data are available on the consistency with clinical diagnoses; thus, we aim at analysing these aspects. Methods: sixty-nine patients with idiopathic inflammatory myopathies (IIM) were studied via LB (Myositis Antigens Profile 3 EUROLINE, Euroimmun) and IP (RNA and protein antigens). The degree of concordance between methods was calculated using Cohen’s coefficient. Results: a substantial concordance was found for anti-Ku and anti-PM/Scl and a moderate concordance was found for anti-Jo1 and anti–Mi-2, while a fair concordance was found for anti-EJ, anti-SRP, and anti-Ro52 antibodies. The concordance could not be calculated for anti-OJ, anti-PL-7, anti-PL-12, anti-NXP2, anti-TIF1ɣ, and anti-MDA5, because they were only detected with one method. Multiple MSAs were found only with LB in 2/69 sera. Anti-MDA5, TIF1ɣ, NXP2 (detected via IP), and anti-Jo1 in anti-synthetase syndrome (both LB and IP) had the best concordance with clinical diagnosis. Conclusions: LB and IP show substantial concordance for PM/Scl and Ku, and moderate concordance for Jo1 and Mi-2, with a good concordance with clinical diagnoses. IP shows a high performance for DM-associated MSAs. LB seems to be more sensitive in detecting anti-Ro52 antibodies, but it identified multiple MSAs, unlike IP. Full article
(This article belongs to the Special Issue Recent Advances in Diagnosis and Treatment in Rheumatology)
10 pages, 271 KiB  
Article
Human Leukocyte Antigen B*27-Negative Spondyloarthritis: Clinical, Serological, and Radiological Features of a Single-Center Cohort
by Francesco Maria Mariani, Alessia Alunno, Evy Di Ruscio, Piera Altieri, Claudio Ferri and Francesco Carubbi
Diagnostics 2023, 13(23), 3550; https://doi.org/10.3390/diagnostics13233550 - 28 Nov 2023
Cited by 2 | Viewed by 1014
Abstract
The strong genetic association between HLA-B*27 and spondyloarthritis (SpA) accounts for about 90% of the susceptibility to axial SpA (axSpA), and the presence of HLA-B*27 is helpful in classifying patients according to the Assessment of SpondyloArthritis International Society (ASAS) classification criteria. However, over [...] Read more.
The strong genetic association between HLA-B*27 and spondyloarthritis (SpA) accounts for about 90% of the susceptibility to axial SpA (axSpA), and the presence of HLA-B*27 is helpful in classifying patients according to the Assessment of SpondyloArthritis International Society (ASAS) classification criteria. However, over the years, other HLA-B alleles have been associated with an increased risk of developing SpA; on this basis, the aim of our study was to describe the demographic, clinical, and radiological characteristics of a cohort of SpA patients who were negative for HLA-B*27. We identified 85 patients with a clinical diagnosis of SpA displaying HLA-B alleles other than HLA-B*27; HLA-B*51 emerged as the most prevalent allele (N = 33, 39%), regardless of the fulfilment of either the axial or the peripheral ASAS criteria. The second most prevalent allele in the full cohort (N = 16, 19%) and in the patients fulfilling either the axial or the peripheral criteria was HLA-B*35. The third most prevalent allele in the full cohort was HLA-B*18 (N = 12, 15%), which was also the second most prevalent allele in the patients fulfilling neither of the two sets of criteria. Overall, the clinical picture was similar across the subgroups fulfilling the different sets of ASAS criteria; however, the patients not fulfilling any ASAS criteria had a higher likelihood of having arthritis compared to the patients fulfilling the axial criteria, whereas the Bath Ankylosing Spondylitis Functional Index was significantly higher in those patients fulfilling the axial criteria compared to those who did not fulfill any criteria. Our results indicate that other HLA alleles, beyond HLA-B*27, could be useful in facilitating SpA diagnosis, particularly in patients with a clinical picture which is consistent with SpA but does not fulfill the ASAS classification criteria. Full article
(This article belongs to the Special Issue Recent Advances in Diagnosis and Treatment in Rheumatology)
13 pages, 696 KiB  
Article
Plasma Dephosphorylated-Uncarboxylated Matrix Gla-Protein in Systemic Sclerosis Patients: Biomarker Potential for Vascular Calcification and Inflammation
by Judith Potjewijd, Rachid Tobal, Karin A. Boomars, Vanessa V. P. M. van Empel, Femke de Vries, Jan G. M. C. Damoiseaux, Leon J. Schurgers and Pieter van Paassen
Diagnostics 2023, 13(23), 3526; https://doi.org/10.3390/diagnostics13233526 - 24 Nov 2023
Cited by 2 | Viewed by 1148
Abstract
Background: Systemic sclerosis (SSc) patients face an elevated risk of cardiovascular disease (CVD), even when classic cardiovascular risk factors are considered. Plasma dephosphorylated-uncarboxylated Matrix Gla-protein (dp-ucMGP), an inactive form of MGP, is associated with increased CVD risk. Smooth muscle cells, implicated in SSc’s [...] Read more.
Background: Systemic sclerosis (SSc) patients face an elevated risk of cardiovascular disease (CVD), even when classic cardiovascular risk factors are considered. Plasma dephosphorylated-uncarboxylated Matrix Gla-protein (dp-ucMGP), an inactive form of MGP, is associated with increased CVD risk. Smooth muscle cells, implicated in SSc’s development, are the primary dp-ucMGP producers. This study assessed dp-ucMGP levels and initial CVD events in early-diagnosed SSc patients, investigating its potential as a CVD and all-cause mortality predictor over time. Methods: In a cohort of 87 SSc patients (excluding those with pre-existing CVD or on dialysis), baseline dp-ucMGP levels were measured, along with cardiovascular risk factors. Validation involved assessing dp-ucMGP in a subset of treatment-naive SSc patients. Results: A significantly elevated median dp-ucMGP level of 634 pmol/L (IQR 301) compared with healthy controls (dp-ucMGP < 393 pmol/L; p < 0.001) was observed. Validation in a treatment-naive SSc patient subset yielded similar results (median 589 pmol/L; IQR 370). During a median 10.5-year follow-up among 78 SSc patients, 33.3% experienced their first CVD event, independent of traditional risk factors. Elevated dp-ucMGP levels (>634 pmol/L) correlated with a higher risk of CVD and/or death (log-rank test: p < 0.01). Conclusions: In summary, dp-ucMGP emerges as a novel biomarker in SSc patients, with elevated levels indicating an increased risk of CVD and/or mortality in this population. Full article
(This article belongs to the Special Issue Recent Advances in Diagnosis and Treatment in Rheumatology)
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13 pages, 764 KiB  
Article
Detection of Myositis Autoantibodies by Multi-Analytic Immunoassays in a Large Multicenter Cohort of Patients with Definite Idiopathic Inflammatory Myopathies
by Anna Ghirardello, Mariele Gatto, Chiara Franco, Elisabetta Zanatta, Roberto Padoan, Luana Ienna, Nicoletta Gallo, Margherita Zen, Ingrid E. Lundberg, Michael Mahler, Andrea Doria and Luca Iaccarino
Diagnostics 2023, 13(19), 3080; https://doi.org/10.3390/diagnostics13193080 - 28 Sep 2023
Cited by 7 | Viewed by 2017
Abstract
Background: The usefulness of myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs) for the assessment of idiopathic inflammatory myopathies (IIMs) is acknowledged, but laboratory standardization remains a challenge. We detected MSAs/MAAs by multi-analytic line immunoassay (LIA) and particle-based multi-analyte technology (PMAT) in a multicenter [...] Read more.
Background: The usefulness of myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs) for the assessment of idiopathic inflammatory myopathies (IIMs) is acknowledged, but laboratory standardization remains a challenge. We detected MSAs/MAAs by multi-analytic line immunoassay (LIA) and particle-based multi-analyte technology (PMAT) in a multicenter cohort of patients with IIMs. Methods: We tested the sera from 411 patients affected with definite IIM, including 142 polymyositis (PM), 147 dermatomyositis (DM), 19 cancer-associated myositis, and 103 overlap myositis syndrome (OM), and from 269 controls. MSAs/MAAs were determined by 16Ags LIA in all sera, and anti-HMGCR by ELISA in 157/411 IIM sera and 91/269 control sera. The analytical specificity of LIA/HMGCR ELISA was compared with that of PMAT in 89 MSA+ IIM sera. Results: MSAs/MAAs were positive in 307/411 (75%) IIM patients and 65/269 (24%) controls by LIA (Odds Ratio 9.26, 95% CI 6.43–13.13, p < 0.0001). The sensitivity/specificity of individual MSAs/MAAs were: 20%/100% (Jo-1), 3%/99.3% (PL-7), 4%/98.8% (PL-12), 1%/100% (EJ), 0.7%/100% (OJ), 9%/98% (SRP), 5.6%/99.6% (TIF1γ), 4.6%/99.6% (MDA5), 8%/96% (Mi-2), 1.5%/98% (NXP2), 1.7%/100% (SAE1), 4%/92% (Ku), 8.5%/99% (PM/Scl-100), 8%/96% (PM/Scl-75), and 25.5%/79% (Ro52). Anti-HMGCR was found in 8/157 (5%) IIM patients and 0/176 (0%) controls by ELISA (p = 0.007). Concordance between LIA/HMGCR ELISA and PMAT was found in 78/89 (88%) samples. Individual MSAs detected by LIA were associated with IIM subsets: Jo-1 with PM and OM, PL-12 with OM, Mi-2, TIF1γ, and MDA5 with DM, SRP with PM, and PM/Scl-75/100 with OM (p < 0.001 for all). Conclusions: Since MSAs are mostly mutually exclusive, multi-specific antibody profiling seems effective for a targeted clinical-serologic approach to the diagnosis of IIMs. Full article
(This article belongs to the Special Issue Recent Advances in Diagnosis and Treatment in Rheumatology)
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10 pages, 931 KiB  
Article
CCL18 as a Biomarker of Interstitial Lung Disease (ILD) and Progressive Fibrosing ILD in Patients with Idiopathic Inflammatory Myopathies
by Elisabetta Zanatta, Andrea Martini, Roberto Depascale, Anna Gamba, Marta Tonello, Mariele Gatto, Chiara Giraudo, Elisabetta Balestro, Andrea Doria and Luca Iaccarino
Diagnostics 2023, 13(10), 1715; https://doi.org/10.3390/diagnostics13101715 - 12 May 2023
Cited by 2 | Viewed by 1728
Abstract
Objectives. To assess CCL18 and OX40L as biomarkers of interstitial lung disease (ILD) and/or progressive fibrosing (PF-) ILD in idiopathic inflammatory myopathies (IIMs). Methods. Patients with IIMs seen in our center from July 2020 to March 2021 were consecutively enrolled. ILD was detected [...] Read more.
Objectives. To assess CCL18 and OX40L as biomarkers of interstitial lung disease (ILD) and/or progressive fibrosing (PF-) ILD in idiopathic inflammatory myopathies (IIMs). Methods. Patients with IIMs seen in our center from July 2020 to March 2021 were consecutively enrolled. ILD was detected by high-resolution CT. CCL18 and OX40L serum levels were measured by validated ELISA assays in 93 patients and 35 controls. At the 2-year follow-up, PF-ILD was evaluated according to the INBUILD criteria. Results. ILD was diagnosed in 50 (53.7%) patients. CCL18 serum levels were higher in IIMs patients vs. controls (232.9 [IQR 134.7–399.07] vs. 48.4 [29.9–147.5], p < 0.0001), with no difference for OX40L. IIMs-ILD patients exhibited higher levels of CCL18 than those without ILD (306.8 [190.8–520.5] vs. 162 [75.4–255.8], p < 0.0001). High CCL18 serum levels were independently associated with IIMs-ILD diagnosis. At follow-up, 22/50 (44%) patients developed a PF-ILD. Patients who developed PF-ILD had higher CCL18 serum levels than non-progressors (511 [307–958.7] vs. 207.1 [149.3–381.7], p < 0.0001). Multivariate logistic regression analysis revealed CCL18 as the only independent predictor of PF-ILD (OR 1.006 [1.002–1.011], p = 0.005). Conclusions. Although in a relatively small sample, our data suggest that CCL18 is a useful biomarker in IIMs-ILD, particularly in the early identification of patients at risk of developing PF-ILD. Full article
(This article belongs to the Special Issue Recent Advances in Diagnosis and Treatment in Rheumatology)
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18 pages, 3942 KiB  
Article
MMP-13, VEGF, and Disease Activity in a Cohort of Rheumatoid Arthritis Patients
by Mihail Virgil Boldeanu, Lidia Boldeanu, Oana Mariana Cristea, Dana Alexandra Ciobanu, Sabin Ioan Poenariu, Anda Lorena Dijmărescu, Andreea Lili Bărbulescu, Vlad Pădureanu, Teodor Nicuşor Sas, Ștefan Cristian Dinescu, Florentin Ananu Vreju, Horațiu Valeriu Popoviciu and Răzvan Adrian Ionescu
Diagnostics 2023, 13(9), 1653; https://doi.org/10.3390/diagnostics13091653 - 8 May 2023
Cited by 1 | Viewed by 2350
Abstract
Identifying certain serum biomarkers associated with the degree of rheumatoid arthritis (RA) activity can provide us with a more accurate view of the evolution, prognosis, and future quality of life for these patients. Our aim was to analyze the presence and clinical use [...] Read more.
Identifying certain serum biomarkers associated with the degree of rheumatoid arthritis (RA) activity can provide us with a more accurate view of the evolution, prognosis, and future quality of life for these patients. Our aim was to analyze the presence and clinical use of matrix metalloproteinase-13 (MMP-13), along with vascular endothelial growth factor (VEGF) and well-known cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) for patients with RA. We also wanted to identify the possible correlations between MMP-13 and these serological markers, as well as their relationship with disease activity indices, quality of life, and ultrasonographic evaluation. For this purpose, we analyzed serum samples of 34 RA patients and 12 controls. In order to assess serum concentrations for MMP-13, VEGF, TNF-α, and IL-6, we used the enzyme-linked immunosorbent assay (ELISA) technique. Our results concluded that higher levels of MMP-13, VEGF, TNF-α, and IL-6 were present in the serum of RA patients compared to controls, with statistical significance. We furthermore identified moderately positive correlations between VEGF, MMP-13, and disease activity indices, as well as with the ultrasound findings. We also observed that VEGF had the best accuracy (97.80%), for differentiating patients with moderate disease activity. According to the data obtained in our study, that although MMP-13, TNF-α and C-reactive protein (CRP) have the same sensitivity (55.56%), MMP-13 has a better specificity (86.67%) in the diagnosis of patients with DAS28(4v) CRP values corresponding to moderate disease activity. Thus, MMP-13 can be used as a biomarker that can differentiate patients with moderate or low disease activity. VEGF and MMP-13 can be used as additional parameters, along with TNF-α and IL-6, that can provide the clinician a better picture of the inflammatory process, disease activity, and structural damage in patients with RA. Our data can certainly constitute a start point for future research and extended studies with multicenter involvement, to support the selection of individualized and accurate therapeutic management strategies for our patients. Full article
(This article belongs to the Special Issue Recent Advances in Diagnosis and Treatment in Rheumatology)
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13 pages, 1590 KiB  
Article
Efficacy and Safety of Nintedanib in Patients with Connective Tissue Disease-Interstitial Lung Disease (CTD-ILD): A Real-World Single Center Experience
by Maria Boutel, Afroditi Boutou, Georgia Pitsiou, Alexandros Garyfallos and Theodoros Dimitroulas
Diagnostics 2023, 13(7), 1221; https://doi.org/10.3390/diagnostics13071221 - 23 Mar 2023
Cited by 7 | Viewed by 2799
Abstract
Connective Tissue Disease-Interstitial Lung Disease (CTD-ILD) is a severe and fatal manifestation of systemic autoimmune disorders. Therapies rely on immunomodulators but their efficacy in ILD progression remains uncertain. Nintedanib, an antifibrotic agent that slows pulmonary function decline, has been approved for CTD-ILD treatment. [...] Read more.
Connective Tissue Disease-Interstitial Lung Disease (CTD-ILD) is a severe and fatal manifestation of systemic autoimmune disorders. Therapies rely on immunomodulators but their efficacy in ILD progression remains uncertain. Nintedanib, an antifibrotic agent that slows pulmonary function decline, has been approved for CTD-ILD treatment. The aim of this study was to assess the effectiveness and safety of nintedanib in CTD-ILD patients in a real-world data setting. A single-center, retrospective, and descriptive analysis of CTD-ILD patients treated with nintedanib from June 2019 to November 2022 was performed. The assessment of nintedanib treatment’s efficacy was judged solely on the evolution of pulmonary function tests (PFTs), which were evaluated before and after treatment. Twenty-one patients (67% females, median age 64 years (IQR = 9) with CTD-ILD (systemic sclerosis n = 9, rheumatoid arthritis n = 5, dermatomyositis n = 4, juvenile rheumatoid arthritis n = 1, undifferentiated CTD n = 1, interstitial pneumonia with autoimmune features n = 1), 18 of whom were on concomitant immunosuppressives, had a median follow-up period of 10 months (IQR = 5). PFTs before and after treatment did not significantly differ. The mean FVC% difference was +0.9 (sd = 7.6) and the mean DLco% difference was +3.4 (sd = 12.6), suggesting numerical improvement of PFTs. The average percentage change was −0.3% and +7.6% for FVC% and DLco%, respectively, indicating stabilization of lung function. Our real-world data across a broad spectrum of CTD-ILD suggest that nintedanib could be beneficial in combination with immunosuppressives in slowing the rate of lung function decline. Full article
(This article belongs to the Special Issue Recent Advances in Diagnosis and Treatment in Rheumatology)
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3 pages, 433 KiB  
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Neurosarcoidosis Masquerading as Spinal Stenosis
by Ameen Batheesh, Nina Borissovsky, Devy Zisman and Tal Gazitt
Diagnostics 2024, 14(20), 2296; https://doi.org/10.3390/diagnostics14202296 - 16 Oct 2024
Viewed by 368
Abstract
A 65-year-old woman was admitted to the neurology department with a suspected demyelinating disease due to complaints of progressive pain and weakness in both upper and lower limbs, as well as urinary incontinence. MRI of the spine revealed complex disc osteophyte with compression [...] Read more.
A 65-year-old woman was admitted to the neurology department with a suspected demyelinating disease due to complaints of progressive pain and weakness in both upper and lower limbs, as well as urinary incontinence. MRI of the spine revealed complex disc osteophyte with compression of the spinal cord in the cervical and lumbar spine at several vertebral levels, and localized enhancement in the cervical spine at the site of maximal spinal canal stenosis. During her hospitalization, the patient underwent extensive evaluation to rule out any systematic inflammatory diseases, infections, and malignancy. Chest CT revealed bilateral mediastinal lymphadenopathy. Transbronchial mediastinal lymph node biopsy showed numerous non-necrotizing granulomas without evidence of malignancy. After a thorough and careful exclusion of a demyelinating, infectious, and paraneoplastic myelopathies, and based on clinical, radiographic, and pathological findings, the patient was diagnosed with both neurosarcoidosis and spondylotic myelopathy. She was then treated for neurosarcoidosis, including glucocorticosteroids, azathioprine, and a biosimilar of the anti-TNF alpha agent infliximab, resulting in both clinical and radiographic improvement. Intramedullary spinal neurosarcoidosis is very rare and may present with clinical features of spondylotic myelopathy, with typical imaging findings occurring only in areas of spinal canal stenosis. Full article
(This article belongs to the Special Issue Recent Advances in Diagnosis and Treatment in Rheumatology)
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