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

Deadline for manuscript submissions: 7 March 2025 | Viewed by 9324

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Dr. Jacopo Ciaffi

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Medicine and Rheumatology Unit, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy
Interests: interventional procedures; rheumatoid arthritis; peripheral spondyloarthritis; metabolic bone diseases; complex regional pain syndrome
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Special Issue Information

Dear Colleagues,

We are pleased to introduce this Special Issue on “Advances in Clinical Rheumatology”, a collection of research and insights into the field of rheumatology. We will focus on a range of pivotal topics that are at the forefront of our evolving understanding and treatment of rheumatic diseases.

The study of rheumatoid arthritis highlights novel therapeutic strategies and emerging concepts in pathogenesis, and we seek to investigate the unique clinical presentations and the challenges in the management of peripheral spondyloarthritis. Papers about interventional procedures, such as radiofrequency ablation and transcatheter arterial embolization, or those covering metabolic bone diseases, from osteoporosis to rarer disorders, are also welcome. With these aims in mind, we will provide insights into new diagnostic modalities and therapeutic interventions for patients with complex regional pain syndrome (CRPS), a perplexing and often debilitating condition.

With this Special Issue we will contribute to the dynamic and ever-advancing field of clinical rheumatology, and we are confident it will inspire continued progress in our understanding and treatment of these challenging conditions.

Dr. Jacopo Ciaffi
Guest Editor

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Keywords

rheumatoid arthritis
spondyloarthritis
interventional
osteoporosis
complex regional pain syndrome

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Published Papers (8 papers)

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22 pages, 3581 KiB

Open AccessArticle

A Real-Life Study in Sequential Therapy for Severe Menopausal Osteoporosis

by Oana-Claudia Sima, Mihai Costachescu, Mihaela Stanciu, Claudiu Nistor, Mara Carsote, Denisa Tanasescu, Florina Ligia Popa and Ana Valea

J. Clin. Med. 2025, 14(2), 627; https://doi.org/10.3390/jcm14020627 - 19 Jan 2025

Viewed by 452

Abstract

Background: Teriparatide (TPT) acts against severe primary (postmenopausal) osteoporosis (MOP), and it requires continuation with another anti-resorptive drug to conserve or enhance the effects on fracture risk reduction. Objective: To analyse the sequential pharmacotherapy in MOP who were treated upon a 24-month daily 20 µg TPT protocol (24-mo-TPT) followed by another 12 months of anti-resorptive drugs (12-mo-AR) amid real-life settings. Hypotheses: 1. TPT candidates had a more severe fracture risk profile versus those who did not fulfil the TPT criteria according to the national protocol of TPT initiation; 2. Patients treated with TPT improved their DXA profile after 24 mo; 3. After 1 year of therapy since the last TPT injection, the improved bone profile and fracture risk at the end of the TPT protocol were conserved; 4. The mineral metabolism assays and fracture risk status were similar at TPT initiation between those who finished the 24 mo protocol and those who prematurely stopped it. Methods: This was a longitudinal, retrospective, multicentre study in MOP. The entire cohort (group A) included the TPT group (B) versus the non-TPT group (non-B). Group B included subjects who finished 24-mo-TPT (group P) and early droppers (ED), and then both continued 12-mo-AR. Results: Group B (40.5%) from cohort A (N = 79) vs. non-B had lower T-scores, increased age and years since menopause. A similar profile of demographic features, BTM, and prevalent fractures (73%, respectively, 57%) was found in group P (72%) vs. ED (21.8%). Group P: osteocalcin was statistically significantly higher at 12 mo (+308.39%), respectively, at 24 mo (+171.65%) vs. baseline (p < 0.001 for each), while at 12-mo-AR became similar to baseline (p = 0.615). The cumulative probability of transient hypercalcemia-free follow-up of protocol had the highest value of 0.97 at 6 mo. An incidental fracture (1/32) was confirmed under 24-mo-TPT. BMD had a mean percent increase at the lumbar spine of +8.21% (p < 0.001), of +12.22% (p < 0.001), respectively, of +11.39% (p < 0.001). The pharmacologic sequence for 12-mo-AR included bisphosphonates (24.24% were oral BP) or denosumab (13%). BTM showed a suppression at 12-mo-AR (p < 0.05), while all BMD/T-scores were stationary. No incidental fracture was registered during 12-mo-AR. Conclusions: All research hypotheses were confirmed. This study in high-risk MOP highlighted an effective sequential pharmacotherapy in reducing the fracture risk as pinpointed by BMD/T-score measurements and analysing the incidental fractures profile. Full article

(This article belongs to the Special Issue Advances in Clinical Rheumatology)

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11 pages, 267 KiB

Open AccessArticle

Do the Activity Indices Used in Axial Spondyloarthritis Capture the Relationships Between Obesity, Smoking and Disease Activity in the Same Way?

by Rubén Queiro, Sara Alonso-Castro, Ignacio Braña, Marta Loredo, Estefanía Pardo, Stefanie Burger, Valentina Chiminazzo and Mercedes Alperi

J. Clin. Med. 2024, 13(22), 6801; https://doi.org/10.3390/jcm13226801 - 12 Nov 2024

Viewed by 706

Abstract

Background/Objectives: Obesity and smoking have been related to increased disease activity in axial spondyloarthritis (axSpA), but these associations might vary depending on the composite index chosen to assess disease activity. We aimed to check this possibility. Methods: Three hundred and thirty consecutive patients were recruited from the monographic axSpA unit of a university center. To assess disease activity, BASDAI and ASDAS-CRP measurements were collected. The factors associated with the different disease activity thresholds of these instruments were analyzed using univariate and multivariate logistic regression models. Results: This study included 127 women and 203 men, with a mean age of 47.6 (SD 12.9) years, median disease duration of 8 years [IQR: 4–16], and 63% on biologic therapies. Most patients met the therapeutic goals, with a BASDAI < 4 in 187 (56.7%) and ASDAS inactive/low category in 182 (55.2%). Being male was associated with BASDAI remission (OR 2.63), but smoking reduced this likelihood (OR 0.28). Similar findings were found for ASDAS inactive disease (male: OR 2.09; smoking: OR 0.39). The variables associated with BASDAI ≥ 4 in the multivariate logistic model were the male gender (OR 0.36), age (OR 1.02), smoking (OR 2.39), and obesity (OR 2.94), whereas those associated with active/very active ASDAS categories were the male gender (OR 0.49), age (OR 1.02), and smoking (OR 2.34). However, obesity was not associated with these higher ASDAS categories (p = 0.183). Conclusions: While the association between smoking and increased disease activity was consistent across all composite activity indices, the obesity–activity relationship was only apparent through the BASDAI. Full article

(This article belongs to the Special Issue Advances in Clinical Rheumatology)

12 pages, 747 KiB

Open AccessEditor’s ChoiceArticle

Elevated Circulating Levels of Gut Microbe-Derived Trimethylamine N-Oxide Are Associated with Systemic Sclerosis

by Karen J. Ho, Lutfiyya N. Muhammad, Linh Ngo Khanh, Xinmin S. Li, Mary Carns, Kathleen Aren, Seok-Jo Kim, Priyanka Verma, Stanley L. Hazen and John Varga

J. Clin. Med. 2024, 13(19), 5984; https://doi.org/10.3390/jcm13195984 - 8 Oct 2024

Cited by 1 | Viewed by 1283

Abstract

Background/Objectives: Alterations in fecal microbial communities in patients with systemic sclerosis (SSc) are common, but the clinical significance of this observation is poorly understood. Gut microbial production of trimethylamine (TMA), and its conversion by the host to trimethylamine N-oxide (TMAO), has clinical and mechanistic links to cardiovascular and renal diseases. Direct provision of TMAO has been shown to promote fibrosis and vascular injury, hallmarks of SSc. We sought to determine levels of TMAO and related metabolites in SSc patients and investigate associations between the metabolite levels with disease features. Methods: This is an observational case:control study. Adults with SSc (n = 200) and non-SSc controls (n = 400) were matched for age, sex, indices of renal function, diabetes mellitus, and cardiovascular disease. Serum TMAO, choline, betaine, carnitine, γ-butyrobetaine, and crotonobetaine were measured using stable isotope dilution liquid chromatography tandem mass spectrometry. Results: Median TMAO concentration was higher (p = 0.020) in SSc patients (3.31 [interquartile range 2.18, 5.23] µM) relative to controls (2.85 [IQR 1.88, 4.54] µM). TMAO was highest among obese and male SSc participants compared to all other groups. Following adjustment for sex, BMI, age, race, and eGFR in a quantile regression model, elevated TMAO levels remained associated with SSc at each quantile of TMAO. Conclusions: Patients with SSc have increased circulating levels of TMAO independent of comorbidities including age, sex, renal function, diabetes mellitus, and cardiovascular disease. As a potentially modifiable factor, further studies examining the link between TMAO and SSc disease severity and course are warranted. Full article

(This article belongs to the Special Issue Advances in Clinical Rheumatology)

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10 pages, 4011 KiB

Open AccessArticle

Nailfold Capillaroscopy Changes in Patients with Idiopathic Inflammatory Myopathies

by Milan Bogojevic, Milica Markovic Vlaisavljevic, Rifat Medjedovic, Elvira Strujic, Dragana Pravilovic Lutovac and Slavica Pavlov-Dolijanovic

J. Clin. Med. 2024, 13(18), 5550; https://doi.org/10.3390/jcm13185550 - 19 Sep 2024

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Abstract

Background/Objectives: Idiopathic inflammatory myopathies (IIMs) are rare autoimmune disorders characterized by progressive proximal muscle weakness and varying extra-muscular manifestations. The latest 2017 EULAR/ACR criteria classify them into subgroups. This study aims to evaluate the role of nailfold capillaroscopy (NFC) as a diagnostic and prognostic tool in IIMs by comparing capillaroscopic patterns across different IIM subtypes. Methods: We conducted an observational, cross-sectional study at the Institute of Rheumatology in Belgrade, analyzing 90 patients diagnosed with IIMs per the 2017 EULAR/ACR criteria. Patients were categorized into dermatomyositis (DM) (n = 37), polymyositis (PM) (n = 35), amyopathic dermatomyositis (ADM) (n = 13), and juvenile dermatomyositis (JDM) (n = 5). A control group of 35 patients with primary Raynaud’s phenomenon was also included. NFC findings, clinical manifestations, and laboratory data were compared across the groups. Results: In DM, 81.9% exhibited a scleroderma capillaroscopic pattern, which was also present in 76.9% of ADM patients. In PM, the most common pattern was nonspecific changes (48.6%). JDM patients showed a high prevalence of scleroderma changes (n = 4 (80%)). Scleroderma patterns correlated with Gottron’s papules, heliotrope rash, periungual erythema, Raynaud’s phenomenon, and interstitial lung disease (ILD). No significant differences were found in laboratory parameters across capillaroscopic groups, except for a higher prevalence of anti-Jo1 antibodies in patients with nonspecific capillaroscopic changes. Conclusions: NFC is a valuable tool for differentiating IIM subtypes and correlating clinical manifestations with specific capillaroscopic patterns. The high prevalence of scleroderma changes in DM and ADM suggests their potential as a diagnostic and prognostic marker in IIMs. Further research with larger cohorts is warranted to validate these findings. Full article

(This article belongs to the Special Issue Advances in Clinical Rheumatology)

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9 pages, 948 KiB

Open AccessArticle

Does the Change of Weather Influence Disease Activity in Rheumatoid Arthritis Patients: Patients’ Self-Assessment via WebApp

by Martin Poller, Martin M. P. Schulz, Hendrik Schulze-Koops, Diego Kyburz, Johannes von Kempis and Ruediger B. Mueller

J. Clin. Med. 2024, 13(17), 5336; https://doi.org/10.3390/jcm13175336 - 9 Sep 2024

Viewed by 815

Abstract

Objectives: The aim was to evaluate the influence of weather parameters on disease activity assessed by Routine Assessment of Patient Index Data (RAPID) scores via a Web-based smartphone application (WebApp). Methods: Correlation of changes of temperature (change of temperature, °C) and air pressure (change of air pressure, hPa) two days prior to and weekly self-assessment of disease activity by RAPID-3 scores over three months. To define background noise and quadrants of weather changes, we defined a central quadrant ± 2 hPa and ± 2° C, called E1. Based on this inner square, four quadrants were defined: A1 = sector left side above with increasing temperature and air pressure (improving weather); B1 = sector right side above; C1 = decreasing temperature and air pressure sector right side down (worsening weather); and D1 = sector left side down. Alterations of RAPID-3 scores analyzed changes in disease activity compared to RAPID-3 scores detected one week in advance. Results: Eighty patients were included in the analysis (median RA duration, 4.5 years; age, 57 years; 59% female). Median disease activity was 2.8 as assessed by DAS 28. In total, 210 time points were analyzed for quadrant A1, 164 for quadrant B1, 160 for quadrant C1, 196 for quadrant D1, and 145 for the inner square E1 were found during follow-up. The middle square E1 was balanced between increasing or decreasing values for RAPID scores. The odds for increasing RAPID scores were 1.33 (95% confidence interval CI: 1.0–1.78) for patients with ameliorating weather conditions which improve or alleviate unfavorable or adverse conditions (A1) compared to 0.98 (CI: 0.67–1.45) for worsening weather (C1) as defined by temperature and air pressure. Conclusions: On average, more patients developed a slight increase of disease activity if they were in the quadrant with increasing temperature and air pressure (improving weather). Thus, no correlation between the worsening of the weather and changing RAPID-3 scores was found. Full article

(This article belongs to the Special Issue Advances in Clinical Rheumatology)

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10 pages, 1190 KiB

Open AccessArticle

Prioritising Appointments by Telephone Interview: Duration from Symptom Onset to Appointment Request Predicts Likelihood of Inflammatory Rheumatic Disease

by Martin Feuchtenberger, Magdolna Szilvia Kovacs, Axel Nigg and Arne Schäfer

J. Clin. Med. 2024, 13(15), 4551; https://doi.org/10.3390/jcm13154551 - 4 Aug 2024

Cited by 1 | Viewed by 855

Abstract

Background: This study aims to determine the rate of inflammatory rheumatic diseases (IRDs) in a cohort of initial referrals and the efficacy of prioritising appointments to the early arthritis clinic (EAC) based on symptom duration. Methods: In the present study, we used algorithm-based telephone triage to assign routine care appointments according to the time between symptom onset and request for an appointment (cut-off criterion: 6 months). This retrospective, monocentric analysis evaluated the effectiveness of our triage in identifying patients with IRDs as a function of the assigned appointment category (elective, EAC, or emergency appointment). Results: A total of 1407 patients were included in the study (34.7% male; 65.3% female). Of the 1407 patients evaluated, 361 (25.7%) presented with IRD. There were significant differences in the frequency of inflammatory diagnoses between appointment categories (p < 0.001): elective 13.8%, EAC 32.9%, and emergency 45.9%. The sample without the emergency category included a total of 1222 patients. The classification into “inflammatory” or “non-inflammatory” in this subsample was as follows: Sensitivity was 37.7%, and specificity was 92.6%. The positive predictive value (PPV) was 59.8%, and the negative predictive value (NPV) was 83.6%. Overall, 80.2% of patients were correctly assigned using the appointment category and C-reactive protein (CRP). Conclusions: The algorithm-based triage system presented here, which focuses on the time between symptom onset and request for an appointment, allows for the prioritisation of appointments in favour of patients with IRDs and thus earlier initiation of therapy. Full article

(This article belongs to the Special Issue Advances in Clinical Rheumatology)

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9 pages, 580 KiB

Open AccessSystematic Review

Sexual Dysfunctions and Gynecomastia in Male Rheumatological Patients Treated with Methotrexate: A Systematic Review

by Luigi Napolitano, Marco Abate, Francesco Di Bello, Simone Morra, Luigi Cirillo, Giovanni Maria Fusco, Gianluigi Califano, Claudia Collà Ruvolo, Massimiliano Creta, Roberto La Rocca, Felice Crocetto, Biagio Barone, Ilenia Pantano, Pierluigi Russo, Davide Arcaniolo and Celeste Manfredi

J. Clin. Med. 2024, 13(21), 6455; https://doi.org/10.3390/jcm13216455 - 28 Oct 2024

Viewed by 879

Abstract

Objectives: The aim of the current review was to elucidate the clinical context and presentation of sexual dysfunction (SD) and gynecomastia in rheumatological patients undergoing methotrexate treatment. Moreover, we aimed also to make physicians aware of the occurrence of these side effects, to adequately inform the patient before starting treatment. Methods: Systematic review (PROSPERO id: CRD42022358275) was performed according to preferred reporting items for systematic reviews and meta-analyses. Studies (1 January 1995 to 31 May 2022) were identified by highly sensitive searches of electronic databases (Medline, Embase, Cochrane Library databases). Key terms included: ((“sexual dysfunction” OR “erectile dysfunction” OR “impotence”) AND (“methotrexate” OR “MTX”)) and ((“gynecomastia” OR “male breast”) AND (“methotrexate” OR “MTX”)). Results: A total of seven papers (seven case reports), involving a total of eleven patients (min one, max three), were included in the final analysis. The age of the patients ranged from 19 to 68 years (median: 50.9 years). Rheumatoid arthritis (RA) was the most frequent rheumatic disease reported (n = 8, 72.7%). No patients reported erectile dysfunction (ED) and/or gynecomastia before using MTX. Time to onset of SD and gynecomastia after MTX ranged from 2 to 104 weeks (median: 22.7 weeks). ED (n = 5, 45.4%) and gynecomastia (n = 3, 27.2%) were the most common forms of presentation. Conclusions: Future prospective controlled studies with a large sample size and long follow-up as well as randomized controlled trials are needed to confirm this association, investigate its pathophysiological basis, assess the safest dosages, evaluate the most appropriate management, and provide clear recommendations. Full article

(This article belongs to the Special Issue Advances in Clinical Rheumatology)

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15 pages, 1147 KiB

Open AccessSystematic Review

Fibromyalgia and Skin Disorders: A Systematic Review

by Martina D’Onghia, Jacopo Ciaffi, Laura Calabrese, Linda Tognetti, Elisa Cinotti, Pietro Rubegni, Bruno Frediani and Francesco Ursini

J. Clin. Med. 2024, 13(15), 4404; https://doi.org/10.3390/jcm13154404 - 27 Jul 2024

Viewed by 2640

Abstract

Background: Fibromyalgia is a complex multifaceted syndrome primarily characterised by chronic musculoskeletal pain, fatigue, and functional symptoms. Although FM is known to be associated with several comorbidities, the aim of this systematic review was to comprehensively examine the available evidence regarding the relationship between FM and dermatological manifestations. Methods: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and MedLine and Web of Science (WOS) databases were searched up to June 2023. After removing duplicate records, 21 articles were deemed eligible for inclusion in the qualitative synthesis. Results: Overall, the included studies revealed an increased frequency of FM among patients with cutaneous diseases, including psoriasis, chronic urticaria, contact allergy, acneiform disorders, hidradenitis suppurativa, and vitiligo. Additionally, the presence of comorbid FM may intensify skin conditions, which has a negative impact on quality of life and vice versa. Conclusions: Although the causal mechanisms of FM are still far from being understood, this systematic review suggests a relationship between FM and skin disorders. However, further research is encouraged in this area. Full article

(This article belongs to the Special Issue Advances in Clinical Rheumatology)

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