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Clinical Treatment and Management of Rheumatic Diseases, Autoinflammatory Diseases, and Autoimmune Disorders

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Immunology & Rheumatology".

Deadline for manuscript submissions: 10 July 2026 | Viewed by 14499

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Prof. Dr. Merav Lidar

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Rheumatology Unit, Sheba Medical Center, Tel-Hashomer, Ramat Gan 5262100, Israel
Interests: imaging in spondyloarthropathies; pregnancy issues in spondyloarthropathies; rheumatoid arthritis; psoriatic arthritis; ankylosing spondylitis
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Abdulla Watad

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Department of Medicine B, Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Ramat Gan 5262100, Israel
Interests: comorbidities of ankylosing spondylitis; early diagnosis of ankylosing spondylitis; new bone formation; prevention of psoriatic arthritis; enthesitis and enthesopathy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Rheumatic and autoimmune disorders present significant challenges in clinical practice. The forthcoming Special Issue of the Journal of Clinical Medicine, which is focused on the "Clinical Treatment and Management of Rheumatic Diseases, Autoinflammatory Diseases, and Autoimmune Disorders", aims to highlight the latest research, innovative treatment strategies, and multidisciplinary approaches in our field.

Through this Special Issue, we hope to foster a deeper understanding of these complex conditions and promote collaboration among researchers and clinicians.

We invite you to submit original research articles and reviews that align with the following themes:

Current advances in treatment protocols and guidelines;
Insights into the management of autoinflammatory diseases;
Innovations in diagnosis and early intervention for autoimmune disorders;
The impact of lifestyle modifications and patient education;
Emerging research and future directions in our field;
Health disparities and access to care.

Prof. Dr. Merav Lidar
Prof. Dr. Abdulla Watad
Guest Editors

Manuscript Submission Information

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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-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly 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 2600 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

rheumatic diseases
autoinflammatory diseases
autoimmune disorders
rheumatoid arthritis
diagnosis

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Published Papers (8 papers)

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14 pages, 2446 KB

Open AccessArticle

Fibrinogen-to-Platelet Ratio and Hematologic Inflammatory Indexes in Spondylarthritis

by Roxana Doina Ungureanu, Cristina Elena Bita, Mirela Nicoleta Voicu, Adina Turcu-Stiolica, Sineta Cristina Firulescu, Mihai Turcu-Stiolica, Andreea Lili Bărbulescu, Stefan Cristian Dinescu and Florentin Ananu Vreju

J. Clin. Med. 2026, 15(8), 2926; https://doi.org/10.3390/jcm15082926 - 12 Apr 2026

Viewed by 540

Abstract

Background/Objectives: Spondylarthritis (SA) is characterized by high clinical heterogeneity, often resulting in a discrepancy between systemic inflammation and patient-reported symptoms. While hematologic indices are emerging as cost-effective biomarkers, their role in phenotypic differentiation remains unclear. We investigated the utility of traditional inflammatory markers, including the novel fibrinogen-to-platelet ratio (FPR), in differentiating SA subtypes and predicting patient-reported disease activity. Methods: This cross-sectional study included 64 patients with spondylarthritis: axial SA (n = 32), peripheral SA (n = 8), and psoriatic SA (n = 24). Clinical assessments included the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Functional Index (BASFI). Systemic inflammation was evaluated via C-reactive protein (CRP), fibrinogen, and calculated ratios (NLR, PLR, MLR, and FPR). Principal Component Analysis (PCA) was employed to map the inflammatory architecture, while Receiver Operating Characteristic (ROC) curves evaluated the predictive power for high disease activity (BASDAI ≥ 4). Results: Significant phenotypic differences were observed with the FPR demonstrating superior discriminative capacity (p = 0.003). Patients with peripheral SA exhibited significantly higher FPR (median 1.88) compared to axial (1.33) and psoriatic (1.32) subtypes, and the dedicated ROC analysis for phenotypic discrimination yielded an AUC of 0.866 (95% CI: 0.745–0.987) (1.36, p = 0.039). HLA-B27 prevalence was low overall (31.3%) and in psoriatic SA (4.2%, p = 0.012). Correlation analysis revealed strong associations between BASDAI and BASFI (ρ = 0.79), NLR and MLR (ρ = 0.78), and CRP and fibrinogen (ρ = 0.66). PCA identified two independent inflammatory dimensions explaining 74.8% of variance: neutrophil-hypercoagulable axis (41.4%, driven by NLR, PLR, and MLR), and an acute-phase/fibrinogen axis (33.4%, driven by CRP, fibrinogen, and FPR). Notably, FPR clustered with acute-phase reactants rather than leukocyte-derived ratios, supporting its role as a marker of systemic inflammatory burden. Although fibrinogen is involved in the coagulation cascade, the absence of direct coagulation markers precludes definitive characterization of this component as hypercoagulable. ROC analysis revealed that fibrinogen showed the highest discriminative ability for disease activity (BASDAI ≥ 4), with an AUC of 0.690 (95% CI: 0.519–0.861), followed by NLR (0.621), MLR (0.592), and FPR (0.583). However, overall discriminative performance remained modest, with most 95% confidence intervals crossing 0.5. Conclusions: FPR emerges as a robust phenotypic biomarker capable of discriminating against SA subtypes, particularly identifying peripheral SA with high accuracy and excellent negative predictive value. In contrast, its ability to predict patient-reported disease activity remains limited, reinforcing the distinction between trait and state biomarkers. Exploratory PCA revealed that FPR clusters with acute-phase reactants rather than leukocyte-derived ratios, supporting its biological link to systemic inflammatory burden. These findings advocate for a dual-purpose biomarker approach in SA: FPR for phenotypic stratification and fibrinogen for activity assessment, while clinical indices remain indispensable for symptom monitoring. Validation in larger, prospective cohorts is warranted. Full article

(This article belongs to the Special Issue Clinical Treatment and Management of Rheumatic Diseases, Autoinflammatory Diseases, and Autoimmune Disorders)

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14 pages, 994 KB

Open AccessArticle

Evaluating the Divide Between Patients’ and Physicians’ Perceptions of Adult-Onset Still’s Disease Cases: Insights from the PRO-AOSD Survey

by Norbert Blank, Ioana Andreica, Jürgen Rech, Zekayi Sözen and Eugen Feist

J. Clin. Med. 2025, 14(19), 7034; https://doi.org/10.3390/jcm14197034 - 4 Oct 2025

Cited by 1 | Viewed by 1113

Abstract

Background/Objectives: This study aims to report and compare data from the PRO-AOSD (patient-reported outcomes adult-onset Still’s disease) survey in patients with AOSD from the perspective of patients and their treating physicians. Methods: PRO-AOSD comprised blinded patient and physician surveys. The surveys were designed to assess perceived symptoms and physical impairment. Outcomes reported here include patient demographics; physicians’ assessment of the patient’s health state; physician-reported laboratory findings; pain; disease activity; symptoms; physicians’ treatment goals; and the impact of lifestyle factors on disease improvement. Results: Adult patients with AOSD were recruited from 19 centers in Germany. A total of 124 patients were included, with 74 (59.7%) females; the mean age was 45.5 years. The mean time from first symptom to diagnosis was 2 years, and the mean time was 7 years from diagnosis to survey completion (N = 123). Of 107 patients, most (81.3%) had inactive disease defined by CRP levels. At the time of the survey, around two-thirds of patients were receiving biologic therapy, with 84.1% (69/82) reporting an improvement in symptoms. Many patients had previously received antibiotics (47.6% [n = 58] and 30.4% [n = 37], per patient and physician reports, respectively). Persistent symptoms were reported more frequently by patients than by physicians, including back pain (39.5%), fatigue and weakness (38.7%), and joint inflammation (27.4%). Physicians classified 35.5% of patients as symptom-free. Patients reported exercise as having a positive impact on symptoms (52.4%), while stress (74.2%) and sleep deprivation (62.9%) were reported to worsen symptoms. Targeting systemic manifestations, such as the absence of fever (58.1%, n = 72), was considered the most important treatment goal by physicians. Conclusions: Data from PRO-AOSD highlight distinct differences between patients’ and physicians’ interpretations of the same cases of AOSD. Prior Presentation: These data were presented at the German Congress of Rheumatology (DGRh; 30 August–2 September 2023; Leipzig, Germany). Full article

(This article belongs to the Special Issue Clinical Treatment and Management of Rheumatic Diseases, Autoinflammatory Diseases, and Autoimmune Disorders)

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9 pages, 202 KB

Open AccessArticle

Pilot Study of AI-Assisted ANA Immunofluorescence Reading—Comparison with Classical Visual Interpretation

by Sarah Mayr, Margit Dollinger, Boris Ehrenstein, Florian Günther, Olga Krammer, Antonia Schuster, Thomas Büttner, Rico Hiemann, Peter Schierack, Dirk Roggenbuck and Martin Fleck

J. Clin. Med. 2025, 14(19), 6924; https://doi.org/10.3390/jcm14196924 - 30 Sep 2025

Cited by 2 | Viewed by 1931

Abstract

Background: Antinuclear antibodies (ANAs) play a crucial role in diagnosing systemic autoimmune rheumatic diseases, particularly systemic lupus erythematosus. The recommended standard for ANA detection is indirect immunofluorescence testing (IIFT) using human epithelial (HEp-2) cells. Since visual interpretation (VI) of IIFT images is time-consuming and labor-intensive, research is focusing on automated interpretation systems that use artificial intelligence (AI). Methods: Consecutive serum samples (number of sera = 143) from routine clinical care were collected from patients visiting our tertiary rheumatology center. ANA were detected by IIFT with visual interpretation and compared with IIFT using the AI-based interpretation system akiron^® NEO (Medipan, 15827 Blankenfelde-Mahlow, Germany). ANA titer levels and patterns were analyzed according to the Competent Level of the International Consensus on ANA Pattern classification. Results: Agreement of positive/negative ANA discrimination between AI-aided and VI-IIFT at the recommended cut-off of 80 was good (Cohen’s kappa [κ] 0.69) but significantly different (McNemar test, p < 0.0001). At a cut-off of ≥1/80, the agreement was improved (κ 0.76) and the difference between both methods was non-significant (p = 1.0000). The ANA pattern recognition agreement between both approaches was moderate (κ = 0.54). The direct comparison using only the akiron^® NEO HEp-2 cell ANA assay revealed a good agreement (0.67), which improved to very good (κ = 0.80) when differences between ANA patterns anti-cell (AC)4/5 and AC2 were neglected. Notably, titer levels in the automated evaluations were frequently assessed at higher values than in the gold standard interpretation. Conclusions: Our study demonstrates a good agreement for positive/negative ANA discrimination. ANA pattern recognition by AI-aided interpretation showed moderate to very good agreement with VI. Further research and algorithm refinement (e.g., improved pattern recognition and titer calibration) are necessary to support its future implementation as a reliable screening method. Full article

(This article belongs to the Special Issue Clinical Treatment and Management of Rheumatic Diseases, Autoinflammatory Diseases, and Autoimmune Disorders)

14 pages, 1017 KB

Open AccessArticle

Evaluation of Nurse-Implemented Self-Management Interventions for Patients with Chronic Inflammatory Arthritis in Bulgaria

by Stefka Stoilova, Mariela Geneva-Popova and Stanislava Popova-Belova

J. Clin. Med. 2025, 14(14), 4854; https://doi.org/10.3390/jcm14144854 - 9 Jul 2025

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Abstract

Objective: To evaluate the role of nurses in self-management interventions for chronic inflammatory arthritis (CIA). Key areas of interest included the following: (1) providing education on self-injection techniques for biologic disease-modifying antirheumatic drugs (bDMARDs), (2) promoting healthy lifestyles, and (3) supporting mental health. Patients’ satisfaction with the care received was also examined. Methods: A cross-sectional study involving CIA patients, rheumatologists, and nurses was conducted. Participants assessed nurses’ competence in areas such as training for bDMARD self-injection, lifestyle guidance, and emotional support. Satisfaction scores and preferences in managing side effects were also analyzed. Results: The participants expressed high confidence in the nurses’ ability to support CIA self-management. The patients rated the nurses significantly higher than doctors in training for self-injection (p = 0.002) and offering guidance on nutrition and healthy habits (p = 0.002). Although it was not a statistically significant difference, the patients also showed stronger trust in the nurses’ ability to provide psychological and emotional support. Most patients (93.0%) would contact a rheumatologist in case of side effects; 35.5% would seek a nurse. The patients attended by both a doctor and nurse reported significantly higher satisfaction compared to those seen only by a rheumatologist (p < 0.001). Both the doctors and nurses acknowledged the importance of the nurse–patient relationship for effective care (p = 0.527). Conclusions: The findings highlight the critical role of nurses in patient education—particularly in training for self-injection and promoting a healthy lifestyle and mental well-being. Their involvement is strongly associated with higher patient satisfaction and contributes significantly to the overall effectiveness of care in CIA management. Full article

(This article belongs to the Special Issue Clinical Treatment and Management of Rheumatic Diseases, Autoinflammatory Diseases, and Autoimmune Disorders)

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14 pages, 1622 KB

Open AccessArticle

Patients with Adult-Onset Still’s Disease in Germany: A Retrospective Analysis of Clinical Characteristics and Treatment Practices Ahead of the Release of the German Recommendations

by Verena Schoenau, Sarah Wendel, Koray Tascilar, Joerg Henes, Eugen Feist, Niklas Thomas Baerlecken, Florian Popp, Matthias Schmidt-Haendle, Bernhard Hellmich, Ina Kötter, Ioana Andreica and Jürgen Rech

J. Clin. Med. 2025, 14(3), 981; https://doi.org/10.3390/jcm14030981 - 4 Feb 2025

Cited by 1 | Viewed by 3632

Abstract

Background/Objectives: Adult-onset Still’s disease (AOSD) is an autoinflammatory disorder that can be challenging to diagnose and manage. The aim of this study was to analyze retrospective data to provide insights into the clinical presentation, disease activity, and treatment patterns and outcomes of AOSD during routine clinical care prior to the release of new AOSD guidelines. Methods: This retrospective database analysis evaluated adult patients (≥18 years) with a diagnosis of AOSD who engaged in a clinical visit between 1 January 2010 and 31 December 2020. The evaluated outcomes included demographic characteristics, symptoms, disease activity, and treatment. Results: Our study included 120 patients (67 [55.8%] of whom were female) diagnosed with AOSD according to the Yamaguchi criteria at ten German rheumatology centers. The median (quartile [Q] 1, Q3) age was 51 (36, 62) years, and the median (Q1, Q3) time from diagnosis was 9 (4, 11) years. Approximately half (66 [55.0%]) had a polycyclic disease course. The most frequent symptoms at initial diagnosis were arthralgia (105 [87.5%]) and fever (86 [71.7%]), and these symptoms continued for a substantial proportion of patients at the current visit (35 [29.2%] and 22 [18.3%], respectively). High neutrophil and ferritin levels were also common. The mean Still Activity Score, a measure of disease activity, improved from 4.66 at initial diagnosis to 1.97 at the most recent visit. The treatments most frequently used at some point in the disease course were glucocorticoids (118 [98.3%]), interleukin (IL)-1 inhibitors (89 [74.2%]), and methotrexate (85 [70.8%]). The most common current treatments were IL-1 inhibitors (55 [45.8%]), followed by methotrexate (29 [24.2%}) and glucocorticoids (28 [23.3%]). Conclusions: Our cohort of patients with AOSD seen at German rheumatology clinics showed strong improvements in symptoms and disease activity from initial diagnosis, but a high symptom burden remained for some patients. Future studies may be able to build on our data to document the impact of new guidelines on treatment patterns. Full article

(This article belongs to the Special Issue Clinical Treatment and Management of Rheumatic Diseases, Autoinflammatory Diseases, and Autoimmune Disorders)

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16 pages, 1106 KB

Open AccessArticle

Association of Immune-Mediated Inflammatory Diseases and Fracture Risk in Patients with Type 2 Diabetes: A Nationwide Population-Based Study

by Yuna Kim, Oh Chan Kwon, Ryul Kim, Jong Hoon Kim, Min-Jae Kim, Min-Chan Park, Jie-Hyun Kim, Young Hoon Youn, Hyojin Park, Kyungdo Han and Jaeyoung Chun

J. Clin. Med. 2025, 14(3), 795; https://doi.org/10.3390/jcm14030795 - 25 Jan 2025

Cited by 2 | Viewed by 1894

Abstract

Background: Immune-mediated inflammatory diseases (IMIDs) are associated with chronic inflammation that may increase fracture risk; however, their impact within specific populations, such as those with type 2 diabetes mellitus (T2DM), remains unclear. This study aimed to evaluate the association between IMIDs and fracture risk, leveraging a large, high-quality population-based cohort of patients with T2DM. Methods: A total of 2,120,900 patients with T2DM without a previous history of fractures were enrolled from the nationwide health check-up database provided by the Korean National Health Insurance Service. The outcomes were overall, osteoporotic, non-osteoporotic, vertebral and hip fractures. Multivariable Cox proportional hazard regression analysis was performed to estimate the adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) according to the presence of IMIDs. Results: The presence of ulcerative colitis (aHR: 1.31), rheumatoid arthritis (aHR: 1.19), ankylosing spondylitis (aHR: 1.32), and psoriasis (aHR: 1.14) were significantly associated with the risk of overall fractures. Compared with controls, patients with a single IMID (aHR: 1.18) and at least two IMIDs (aHR: 1.29) had a significantly increased risk of overall fractures, showing a dose–response relationship. Similar results were observed for osteoporotic, vertebral, and hip fractures. Conclusions: The presence of IMIDs in patients with T2DM was associated with an increased risk of fractures, particularly osteoporotic, vertebral, and hip fractures. This study highlights the significant impact of IMIDs on fracture risk within a diabetic population, emphasizing the need for careful monitoring and tailored management strategies. Full article

(This article belongs to the Special Issue Clinical Treatment and Management of Rheumatic Diseases, Autoinflammatory Diseases, and Autoimmune Disorders)

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13 pages, 1084 KB

Open AccessCase Report

Towards New Strategies: Case Report and Review of the Literature—Effective Use of JAK Inhibitor Baricitinib in a 4-Year-Old Boy with Anti-MDA5 Antibody-Positive Juvenile Dermatomyositis

by Oana Buzoianu, Özlem Satirer, Jasmin B. Kuemmerle-Deschner and Christiane Reiser

J. Clin. Med. 2026, 15(2), 709; https://doi.org/10.3390/jcm15020709 - 15 Jan 2026

Viewed by 962

Abstract

Juvenile dermatomyositis (JDM) is a rare, idiopathic autoimmune disorder characterized by inflammation of both muscle and skin, with a significant contribution from the interferon (IFN) pathway in its pathogenesis. Here, we present the case of a 4-year-old boy with JDM who tested positive for Mi2-α and MDA5 antibodies and showed combined muscle and skin involvement. In view of his markedly elevated IFN signature, the Janus kinase (JAK) inhibitor baricitinib was introduced very early as a targeted steroid-sparing agent in addition to standard immunosuppressive therapy. The patient experienced marked clinical improvement, with resolution of skin lesions, normalization of MDA5 antibodies, and a pronounced reduction in the IFN signature. This case highlights the potential efficacy of JAK inhibition in managing JDM with a high IFN signature and supports a mechanism-based, interferon-targeted treatment approach, in line with emerging evidence in refractory JDM. Further studies are warranted to define the role of JAK inhibitors in the treatment of JDM. Full article

(This article belongs to the Special Issue Clinical Treatment and Management of Rheumatic Diseases, Autoinflammatory Diseases, and Autoimmune Disorders)

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21 pages, 8190 KB

Open AccessPerspective

A Lymphatic Perspective on Obesity and Inflammatory Arthritis: New Disease-Modifying Potential in Rheumatology

by Hannah den Braanker, Eline S. van der Valk and Radjesh J. Bisoendial

J. Clin. Med. 2025, 14(21), 7641; https://doi.org/10.3390/jcm14217641 - 28 Oct 2025

Viewed by 1882

Abstract

Recent studies show that obesity significantly increases disease severity and progression in several forms of inflammatory arthritis, including rheumatoid arthritis (RA), psoriatic arthritis (PsA) and gout. Obesity increases the risk for developing inflammatory arthritis. Similarly, obesity negatively impacts disease severity and treatment outcomes. The underlying mechanisms driving these relationships are not fully understood. One emerging area of investigation is the role of the lymphatic vasculature. Obesity profoundly impacts lymphatic function. Excess adipose tissue can compress and disrupt lymphatic vessels, leading to impaired flow and drainage. Additionally, obesity-associated inflammation and metabolic dysregulation have been linked to lymphatic endothelial cell dysfunction, further compromising transport and immunoregulatory capacities. This impairment fosters an environment for the accumulation of inflammatory cells and mediators, sustaining chronic inflammation. In this review, we will provide new perspectives on the detrimental triangle of obesity, lymphatic dysfunction, and inflammation in chronic inflammatory arthritis and find new starting points for therapeutics. Full article

(This article belongs to the Special Issue Clinical Treatment and Management of Rheumatic Diseases, Autoinflammatory Diseases, and Autoimmune Disorders)

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