Rheumato doi: 10.3390/rheumato6020010

Authors: Alessia Gatti Giulia Fontana Jacopo Mora Franco Franceschini Ilaria Cavazzana Paola Toniati Francesca Regola

Background/Objectives: Dupilumab is a fully human IgG4 monoclonal antibody targeting the interleukin-4 receptor α subunit, inhibiting interleukin-4 and interleukin-13 signalling, and suppressing type 2 inflammation. It is approved for several eosinophilic and type 2 inflammatory diseases, including chronic rhinosinusitis with nasal polyps, asthma, atopic dermatitis, eosinophilic oesophagitis, and, more recently, eosinophilic chronic obstructive pulmonary disease. Although generally well tolerated, dupilumab has been associated with peripheral eosinophilia and, rarely, eosinophil-mediated complications. This study aims to describe cases of eosinophilic granulomatosis with polyangiitis (EGPA) occurring after dupilumab initiation and to review available evidence on this association. Methods: We describe two cases of new-onset EGPA developing after the introduction of dupilumab therapy, analysing clinical features, laboratory findings, management, and outcomes. A narrative review of published case reports and literature addressing dupilumab-associated eosinophilia and EGPA was also performed. Results: Both patients developed EGPA after starting dupilumab, presenting with marked peripheral eosinophilia and systemic manifestations consistent with the disease. Clinical improvement was observed following dupilumab discontinuation and initiation of appropriate immunosuppressive treatment. The literature review identified a small number of similar reports describing EGPA onset or unmasking in temporal association with dupilumab, mainly in patients with underlying type 2 inflammatory disorders. Conclusions: While a causal relationship between dupilumab and EGPA remains unproven, these findings highlight the importance of clinical awareness. Dupilumab remains an effective therapy for severe type 2 inflammatory diseases; careful monitoring may allow early recognition and management of rare eosinophilic complications.

Rheumato doi: 10.3390/rheumato6020009

Authors: Jyothi Ranga Patri Sastry Chamarthi Venkata Sushma Chamarthi

Juvenile idiopathic arthritis (JIA) is among the most prevalent chronic inflammatory rheumatic diseases in children. Over the past two decades, the treatment landscape has evolved significantly with the introduction of biologic disease-modifying antirheumatic drugs and the adoption of treat-to-target strategies aimed at achieving clinically inactive disease. Early initiation of biologic therapies can facilitate rapid disease control and improve long-term outcomes. However, the implementation and integration of newer treatments within the current healthcare system are often hindered by insurance authorization requirements, high costs, and variability in clinical practice. This review evaluates current evidence-based approaches supporting the treat-to-target strategy and early biologic intervention in polyarticular JIA. Additionally, it discusses the practical challenges of translating evidence into routine clinical care and proposes sustainable strategies to optimize treatment outcomes while addressing existing knowledge and practice gaps.

Rheumato doi: 10.3390/rheumato6010008

Authors: Ichiro Yoshii Naoya Sawada Tatsumi Chijiwa

Objectives: The evidence for treating rheumatoid arthritis (RA) with a treat-to-target (T2T) approach was examined for clinical outcomes. Methods: Since August 2010, RA treatment has implemented the T2T strategy, aiming to achieve a simplified disease activity index (SDAI). The SDAI, Health Assessment Questionnaire Disability Index (HAQ), and pain score (PS-VAS) were monitored. The relationships between these clinical outcomes and variables, including changes in medication, were investigated. Results: Over a 15-year follow-up of 764 RA patients, the total duration was divided into two periods for each outcome. In the First period, the average dose of methotrexate (MTX) increased (p < 0.001). At the same time, glucocorticoids use (GCs) decreased (p < 0.001), and biologic and targeted synthetic disease-modifying anti-rheumatic drugs (bDMARDs and tsDMARDs) use increased (p < 0.01). Consequently, the mean SDAI score declined (p < 0.001), which was attributed to an increase in MTX dose and a decrease in GCs use, However, HAQ scores increased (p < 0.01), and PS-VAS remain stable. In the Second period, the average MTX dose decreased despite stable SDAI and decreasing HAQ scores and PS-VAS (p < 0.01), which was attributed to an increase in the use of tsDMARDs, particularly baricitinib, upadacitinib, and filgotinib (p < 0.01). Overall, the average age increased (p < 0.001), while SDAI scores dropped (p < 0.001), and HAQ scores and PS-VAS decreased (p < 0.01). Conclusions: Clinical outcomes stayed stable with changes in medication use under the T2T approach.

Rheumato doi: 10.3390/rheumato6010007

Authors: Ichiro Yoshii Tatsumi Chijiwa Naoya Sawada

Background/Objectives: The short-term effect of Janus kinase inhibitors (JAKis) on renal function in patients with rheumatoid arthritis (RA) was examined in a hypothesis-generating, exploratory study. Methods: RA patients treated with JAK inhibitors and, as a control group, those receiving golimumab and continuing treatment for one or more years were enrolled. They were monitored every 3 months for disease activity using the Simplified Disease Activity Index (SDAI), functional capacity using the Health Assessment Questionnaire Disability Index (HAQ), and renal function using the estimated glomerular filtration rate (eGFR) calculated from creatinine (Cr) and cystatin C (CysC). Patients were categorized by medication, and average values were computed. Two groups for each drug were then compared statistically. Results: A total of 144 patients were analyzed: 24 on tofacitinib, 43 on baricitinib, 21 on upadacitinib, 21 on filgotinib, and 35 on golimumab. Background factors did not differ significantly among groups. Improvements in CDAI and HAQ at any time point also showed no significant differences. eGFR based on Cr showed a significant decline in the baricitinib and filgotinib groups at one year after starting JAKi treatment compared with the other JAKi groups; however, there was no significant difference when using CysC. Conclusions: These results indicate that there is no significant difference in renal function decline among the JAKi drugs over a short period, despite differences in their metabolic pathways and renal excretion patterns.

Rheumato doi: 10.3390/rheumato6010006

Authors: Lisa Gamalero Teresa Giani

Background: Autoinflammatory bone disorders are rare, non-infectious inflammatory conditions that primarily involve the skeleton, most commonly presenting as chronic nonbacterial osteomyelitis (CNO) or chronic recurrent multifocal osteomyelitis (CRMO). Less frequently, they occur in the context of Mendelian syndromes such as Majeed syndrome, deficiency of the interleukin-1 receptor antagonist (DIRA), and pyogenic arthritis; pyoderma gangrenosum; and acne (PAPA) syndrome. Given the role of IL-1-driven innate immune dysregulation across these bone disorders, and the growing, though heterogeneous, clinical experience with IL-1 blockade, this review maps and critically appraises the available evidence on canakinumab in autoinflammatory bone disorders. Methods: We systematically searched PubMed and the Cochrane Library (English, inception–July 2025) and screened ClinicalTrials.gov. Eligible reports included any case reports/series describing canakinumab use in autoinflammatory bone disorders (CNO/CRMO, Majeed, DIRA, PAPA). Results: Six publications met the inclusion criteria (one case series, five case reports; 10 patients). Complete responses were reported in all three patients with Majeed syndrome and in two patients with sporadic CRMO associated with systemic features. Partial responses occurred in two additional sporadic CRMO cases, while no meaningful response was documented in DIRA. No interventional trials of canakinumab were identified on ClinicalTrials.gov for CNO/CRMO, Majeed, DIRA, or PAPA. Conclusions: Although the role of IL-1 in the pathogenesis of autoinflammatory bone disease provides a rationale for IL-1 blockade, evidence for canakinumab remains limited and heterogeneous, precluding definitive conclusions. Indicators of benefits appear most consistently in Majeed syndrome and in selected CRMO phenotypes.

Rheumato doi: 10.3390/rheumato6010005

Authors: Sebastián Eustaquio Martín Pérez Jennifer Díaz García David García Linares Luis Gabriel Barboza Baldó Isidro Miguel Martín Pérez

Background/Objectives: Fibromyalgia syndrome (FMS) is a chronic condition characterized by widespread pain, fatigue, sleep disturbances, and psychological symptoms. Aquatic exercise offers the benefits of physical activity with reduced mechanical stress. This meta-analysis evaluated the effectiveness of AE on pain, functional physical status, and health-related quality of life. Methods: A PRISMA-guided systematic review and meta-analysis (PROSPERO CRD42025115158) included randomized and non-randomized trials up to October 2025 from MEDLINE (PubMed), Cochrane Library, PEDro, CINAHL Complete, SPORTDiscus, and Academic Search Ultimate. Eligible participants were adults diagnosed with FMS undergoing AE programs, alone or combined with other modalities. Standardized mean differences (SMD) with 95% confidence intervals were pooled using random- or fixed-effects models. Methodological quality, risk of bias, and certainty of evidence were evaluated using the PEDro scale, the RoB 2.0 tool, and the GRADE approach. Results: 27 trials (n = 1785; >95% women; mean age 44–62 years) were included. AE significantly improved pain (SMD = −0.92; 95% CI: −1.03 to −0.80; p < 0.00001), physical function (SMD = −0.74; 95% CI: −0.84 to −0.63; p < 0.00001), and HRQoL (SMD = 0.57; 95% CI: 0.42 to 0.72; p < 0.00001). Effects were consistent across time frames, though overall heterogeneity was considerable (Tau2 = 4.93; I2 = 97%). The mean PEDro score was 5.2/10, and RoB 2.0 indicated moderate methodological limitations mainly due to a lack of blinding. Evidence certainty was low for the main outcomes and moderate for adverse events. Conclusions: Aquatic exercise is an effective and safe complementary therapy for patients with FMS, alleviating pain while enhancing function and quality of life. However, methodological variability and small sample sizes warrant further high-quality trials to confirm these findings and explore underlying mechanisms.

Rheumato doi: 10.3390/rheumato6010004

Authors: Hilal Abdessamad

Background: Immunomodulatory therapies, including biologic and targeted synthetic disease-modifying antirheumatic drugs (DMARDs) have reshaped the treatment of autoimmune diseases. They alter host defenses, but the current landscape of associated infectious risk is not fully defined. Objective: A scoping review of recent literature was conducted to characterize infectious complications associated with modern immunomodulatory biologic agents, summarize current pathogen patterns, and highlight recommendations for prevention and early recognition in clinical practice. Methods: Following PRISMA-ScR guidelines, a systematic search was performed on Scopus, Science Direct, and PubMed for studies published since 2023. Inclusion criteria focused on adult human subjects, exposure to immunomodulatory therapy, and reported infectious outcomes. Studies focusing exclusively on antineoplastic agents without established use in autoimmune diseases were excluded. After screening 1046 unique records, 16 studies were included in the final review. Findings: High-dose glucocorticoids remain a primary driver of serious infections across autoimmune diseases. Newer agents present mechanism-specific risk profiles. JAK inhibitors are associated with herpes zoster, while TNF-α inhibitors are linked to opportunistic bacterial infections and reactivation of granulomatous infections. B-cell depletion with rituximab correlates with hypogammaglobulinemia and its associated infections, whereas belimumab may offer a lower infection risk in non-renal SLE. Recent post hoc analyses (2023–2025) quantify the elevated risk of herpes zoster with JAK inhibitors compared to TNF inhibitors, particularly in older populations. Conclusions: The infectious risk associated with biologic and targeted DMARDs varies by mechanism. While glucocorticoids remain a primary driver of serious infections, newer data highlights specific vulnerabilities with JAK inhibitors (herpes zoster) and B-cell depletion (hypogammaglobulinemia) that require targeted risk stratification. This review shows the urgent need for individualized risk stratification, targeted prophylaxis (e.g., for Pneumocystis or zoster), and pre-therapy screening to balance therapeutic efficacy with patient safety.

Rheumato doi: 10.3390/rheumato6010003

Authors: Ellen Frances O’Carroll Annalisa Marino Stefano Di Donato

Pain catastrophizing (PC) and hopelessness are increasingly recognized as central determinants of pain severity, disability, and treatment response in individuals with rheumatic and immune-mediated diseases. Traditionally conceptualized as secondary emotional reactions to pain, these cognitive-affective constructs instead represent active mechanisms that shape symptom perception, behavioral responses, and long-term outcomes. In this review, we synthesize evidence across neurobiological, psychological, and clinical domains to elucidate the pathways linking PC and hopelessness to maladaptive coping, kinesiophobia, and functional decline. Early life stress, trauma, and maladaptive cognitive schemas emerge as upstream vulnerability factors that prime heightened emotional reactivity and reduced prefrontal regulatory control, facilitating amplified pain signaling and fear-based avoidance behaviors. Avoidance and inactivity foster physical deconditioning, fatigue, and higher perceived disability, creating a vicious circle that sustains distress and poor quality of life. Moreover, inactivity-related metabolic dysfunction and weight gain may contribute to low-grade inflammation, particularly in conditions such as psoriatic arthritis, thereby intersecting with biological disease pathways. Importantly, these psychological processes identify a distinct patient subgroup for whom further escalation of immunosuppressive therapy provides limited benefit. Instead, integrated psychological approaches—including cognitive behavioral therapy, acceptance and commitment therapy, and coping-skills training—demonstrate meaningful effects on catastrophizing, agency, and functional recovery. We emphasize the need for routine screening to detect patients with maladaptive cognitive–emotional profiles and propose a stratified care model prioritizing targeted psychological interventions alongside standard rheumatologic therapy. Future research should refine phenotyping strategies, clarify neuroimmune links, and develop scalable intervention models to break the avoidance cycle and improve patient-centered outcomes.

Rheumato doi: 10.3390/rheumato6010002

Authors: Daniela Santos Silva Charlotte de Vries Karin Lundberg Isabel Poiares Baptista José António Pereira da Silva Marta Kaminska Piotr Mydel

Background/Objectives: The aim of this study was to assess the relationship between the decline in rheumatoid arthritis (RA) disease activity—induced by periodontal treatment—and changes in the microbiology of subgingival plaque and serum antibody levels against the periodontal bacterium Porphyromonas gingivalis. Methods: Twenty-two RA patients with periodontitis underwent non-surgical periodontal treatment and assessment for the disease activity score of 28 joints (DAS28); antibody response to P. gingivalis virulence factors arginine (Rgp) and lysin (Kgp) gingipain; peptidyl arginine deiminase (PAD)2/4-activity; and the presence of P. gingivalis, Tannerella forsythia, and Prevotella intermedia in subgingival plaque through the evaluation of colony-forming units (CFUs) at baseline, two months, and six months post-treatment. Results: Periodontal treatment significantly reduced P. gingivalis CFUs at two and six months, and T. forsythia and P. intermedia CFUs at two months. Anti-RgpB IgG levels decreased at two months (p = 0.020). Higher baseline anti-RgpB IgG levels (r = −0.44, p = 0.039) and P. gingivalis CFU (r = −0.47, p = 0.028) correlated with greater reductions in DAS28. Greater reductions in P. gingivalis CFU were also associated with greater declines in DAS28 (r = 0.426, p = 0.048 and r = 0.467, p = 0.028, at two and six months, respectively). Anti-Kgp IgG and PAD2/PAD4 activity were not significantly affected by periodontal treatment. Conclusions: The impact of periodontal treatment on RA disease activity is more pronounced in patients with higher baseline P. gingivalis load and antibody response to RgpB. Better microbiological responses to periodontal treatment are associated with greater improvements in rheumatological symptoms. Further research is needed to confirm these findings and fully elucidate the underlying mechanisms.

Rheumato doi: 10.3390/rheumato6010001

Authors: Ichiro Yoshii Naoya Sawada Tatsumi Chijiwa

Background/Objectives: Associations between renal function, as measured by the estimated glomerular filtration rate (eGFR) or its decline (dGFR), and clinical parameters in patients with rheumatoid arthritis (RA) were evaluated using a retrospective case–control series dataset. Methods: Patients with RA who followed up for one or more consecutive years were recruited for the study. For calculating the eGFR, cystatin C (CysC) was adopted. The moment when CysC was measured was set as the baseline. The association between the eGFR and baseline clinical parameters, including disease activity in RA as measured by the simplified disease activity index (SDAI), was statistically evaluated. The association between the mean annual decline in the eGFR from the baseline and clinical parameters was also statistically assessed. Results: A total of 513 patients were enrolled; with a mean age of 70.9; a mean follow-up length of 52.5 months; a mean BMI of 22.9; a 68.7 eGFR; and a mean annual dGFR of 2.74. Significant parameters that correlated with the eGFR were age; rheumatoid factor titer; C-reactive protein; the presence of hypertension; chronic heart failure; chronic obstructive pulmonary disease; type 2 diabetes mellitus; methotrexate administration; and polypharmacy at baseline. An annual dGFR was correlated with the follow-up length, and the mean SDAI score multiplied by the yearly length of the follow-up was significantly correlated. Conclusions: Many factors confound the determination of the eGFR in RA patients. The disease activity score and length of time are the key factors for declining eGFRs.

Rheumato doi: 10.3390/rheumato5040017

Authors: Ola A. Al-Ewaidat Moawiah M. Naffaa

Background/Objectives: Autoimmune rheumatic diseases (AIRDs) are complex, heterogeneous, and relapsing–remitting conditions in which early diagnosis, flare prediction, and individualized therapy remain major unmet needs. This review aims to synthesize recent progress in AI-driven, biomarker-based precision medicine, integrating advances in imaging, multi-omics, and digital health to enhance diagnosis, risk stratification, and therapeutic decision-making in AIRD. Methods: A comprehensive synthesis of 2020–2025 literature was conducted across PubMed, Scopus, and preprint databases, focusing on studies applying artificial intelligence, machine learning, and multimodal biomarkers in rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, spondyloarthritis, and related autoimmune diseases. The review emphasizes methodological rigor (TRIPOD+AI, PROBAST+AI, CONSORT-AI/SPIRIT-AI), implementation infrastructures (ACR RISE registry, federated learning), and equity frameworks to ensure generalizable, safe, and ethically governed translation into clinical practice. Results: Emerging evidence demonstrates that AI-integrated imaging enables automated quantification of synovitis, erosions, and vascular inflammation; multi-omics stratification reveals interferon- and B-cell-related molecular programs predictive of therapeutic response; and digital biomarkers from wearables and smartphones extend monitoring beyond the clinic, capturing early flare signatures. Registry-based AI pipelines and federated collaboration now allow multicenter model training without compromising patient privacy. Across diseases, predictive frameworks for biologic and Janus kinase (JAK) inhibitor response show growing discriminatory performance, though prospective and equity-aware validation remain limited. Conclusions: AI-enabled fusion of imaging, molecular, and digital biomarkers is reshaping the diagnostic and therapeutic landscape of AIRD. Standardized validation, interoperability, and governance frameworks are essential to transition these tools from research to real-world precision rheumatology. The convergence of registries, federated learning, and transparent reporting standards marks a pivotal step toward pragmatic, equitable, and continuously learning systems of care.

Rheumato doi: 10.3390/rheumato5040016

Authors: Nira Ferdous Md. Nazrul Islam Abu Talha Mustakim Johannes J. Rasker

Introduction: In hemoglobinopathies, the amount of globin synthesis in hemoglobin (Hb) or its structure is altered. Clinical features are related to the rate and kind of structural aberrations. The heterozygous form of the Lepore syndrome resembles minor thalassemia both clinically and hematologically. On electrophoresis, abnormal Hb Lepore fractions are found at a rate of 5–15%, with a mildly higher percentage of HbF and lower HbA. In general, Hb Lepore heterozygotes are asymptomatic. Case presentation: A 32-year-old male was admitted to our hospital with complaints of pain and swelling in multiple large joints and high-grade fever for 11 days. His past history was unremarkable; one of his sisters had the β-thalassemia trait. On physical examination, he was moderately anemic, with mild hepatomegaly and normal spleen; both knees and ankles were tender and swollen. Laboratory showed mild microcytic hypochromic anemia with variables similar to the thalassemia trait and signs of inflammation with very high CRP, serum ferritin, and leukocytosis. Blood sugars were increased. Hb electrophoresis showed an abnormal pattern with mild elevation in HbS, normal Hb F, mild reduction in HbA, and high HbA2, compatible with heterozygosity for the Hb Lepore beta chain variant. He was initially diagnosed with diabetes (treated with insulin) and sepsis from unknown origin, but fever and joint pains did not respond to NSAIDs or antibiotics. He had very good response on high-dose methylprednisolone. Undifferentiated arthritis was diagnosed in the patient with Hb Lepore, and he was treated with oral prednisolone and sulfasalazine (SSZ). At follow up, the patient was doing well. He refused further investigations and did not allow testing on his family members. In summary: Hb Lepore is a rare hemoglobinopathy linked to thalassemia, which may manifest with musculoskeletal problems. Our patient with the Hb Lepore trait presented with undifferentiated polyarthritis and fever, but in our case, a causal relationship remains unclear. This is one of the first adult cases of Hb Lepore in Bangladesh and the first with arthritis of unknown origin. The prevalence of Hb Lepore in Bangladesh is unknown.

Rheumato doi: 10.3390/rheumato5040015

Authors: Alessandro Conforti Carlos Cifuentes-González Alarico Ariani Alberto Lo Gullo Rupesh Agrawal

Background: Chimeric Antigen Receptor T-cell (CAR-T) cell therapy has revolutionized cancer treatment and is now being explored as a novel approach to treat refractory autoimmune diseases by targeting autoreactive immune components, especially B cells. Objective: Our aim was to provide a narrative review of the current evidence, mechanisms, efficacy, safety, and future directions of CAR-T cell therapy in autoimmune diseases. Methods: A structured literature search was conducted in MEDLINE via PubMed using keywords such as “CAR-T”, “chimeric antigen receptor T-cell”, “autoimmune diseases”, “lupus”, “rheumatoid arthritis”, “multiple sclerosis”, and “vasculitis”. Studies on CAR-T mechanisms, efficacy, safety, and clinical outcomes were included. Results: CAR-T cell therapies, especially CD19-directed constructs, demonstrated sustained drug-free remission in all patients across early SLE case series (n = 5–7), with normalization of serological markers and improved renal outcomes. Emerging preclinical and early clinical data in rheumatoid arthritis, multiple sclerosis, ANCA-associated vasculitis, juvenile autoimmune diseases, and idiopathic inflammatory myopathies also report clinical improvement and biomarker normalization. Reported adverse events in autoimmune cohorts were limited to mild cytokine release syndrome in a minority of cases, with no severe neurotoxicity or life-threatening infections, suggesting a more favorable safety profile compared to oncology settings. In parallel, next-generation innovations—including dual-target CARs, CAR-Tregs, and molecular safety switches—are advancing toward clinical translation. Conclusions: CAR-T cell therapy is emerging as a transformative strategy for autoimmune disease management, especially in refractory cases. Although initial outcomes are promising, long-term safety, cost-effectiveness, and broader accessibility remain key challenges. Future research should focus on optimizing cell targets, minimizing off-target effects, and improving affordability.

Rheumato doi: 10.3390/rheumato5040014

Authors: Chiara Baldini Maurice Flurie Zachary Cline Colton Flowers Coralie Peter Bouillot Linda J. Stone Lauren Dougherty Christopher DeFelice Maria Picone

Background/Objectives: Sjögren’s disease (SjD) flares are incompletely understood. The patient perspective is critical to closing this gap. This retrospective social media listening (SML) study characterized the flare lexicon within the online Reddit SjD community using novel machine learning and natural language processing. Methods: Documents (posts/comments) were analyzed from the subreddit group “r/Sjogrens” (October 2012 to August 2023). Outcomes were as follows: (1) Frequency of documents mentioning flare, and contexts in which flare was mentioned; (2) clinical concepts associated with flare (analyzed using co-occurrence and pointwise mutual information [PMI]); (3) proportion of flare vs. non-flare documents relevant to SYMPTOMS or TESTING (compared using a two-proportion z-test); and (4) primary emotions mentioned in flare documents. Results: Of 59,266 documents with 5025 authors, flare was mentioned 3330 times (4.4% of documents from 19.1% of authors). Flare was discussed as a symptom (1423 instances), disease (13), or with no clinical category (1890). Flare-associated clinical concepts (co-occurrence > 100 and PMI2 > 3) included SYMPTOMS (pain, fatigue, dryness of eye, xerostomia, arthralgia, stress) and BODY PARTS (eye, mouth, joints, whole body). More flare vs. non-flare documents mentioned a SYMPTOM, whereas fewer mentioned a TEST (p < 0.001 for both). Within flare documents, 36.5% expressed emotions, primarily fear (40.5% of primary emotions), happiness (17.8%), sadness (15.7%), and anger (15.5%). Conclusions: The SjD community discusses flare frequently and in context with symptoms, specifically pain, eye and mouth dryness, and fatigue. Flare conversations frequently involve negative emotions. Additional research is required to clarify the patient experience of flare, its clinical parameters, and implications.

Rheumato doi: 10.3390/rheumato5030013

Authors: Fabiola Cappella Alessandro Di Rienzo Mario Chiapponi Valentina Liverotti Mauro Dobran

Aim of the study: This paper focuses on the correlation of nicotine use with chronic lumbar back pain (CLBP). Methods: This is a cross-sectional observational study involving smoker and non-smoker patients with a diagnosis of chronic low back pain (CLBP), recruited during their initial neurosurgical consultation at the Neurosurgery Clinic over a period of 6 months. All patients were followed for a minimum of 3 months after the start of conservative therapy. Age, sex, smoking habits, and the presence of any comorbidities were noted. Pain severity and discomfort were evaluated using the Numeric Rating Scale (NRS), the DN4 questionnaire, and the Oswestry Disability Index (ODI). Based on imaging (MRI of the lumbosacral spine), diagnoses of disc herniation or vertebral lumbar stenosis were documented. Statistical analysis was performed using IBM SPSS Statistics software (Version 30). A p-value of less than 0.05 was considered statistically significant. Results: Improvement on the CLBP, NRS, and DN4 scales after the same conservative therapy was better in Patients with non-smoking habits improved more on the CLBP, NRS and DN4 scales when compared to smokers (NRS scale 0.001 and DN4 scale 0.027). Conclusions: Patients with smoking habitudes affected by lumbar disk her-niation and stenosis and undergoing conservative therapy had worse pain scores

Rheumato doi: 10.3390/rheumato5030012

Authors: Trevor Lewis William J. Gregory

Living with inflammatory arthritis can have a significant impact; early identification, diagnosis and treatment has been shown to improve outcomes. The clinician working in settings where people with undiagnosed inflammatory arthritis may present for assessment has a crucial role in early identification and onwards referral. Inflammatory arthritis varies in its presentation with respect to gender. Rheumatoid arthritis tends to affect females more than males; historically, Axial Spondyloarthropathy was felt to predominately affect males but the distribution is now known to be equal between men and women. Psoriatic arthritis also affects males and females without obvious sex prevalence. Objectives: To investigate, through a narrative literature review, the early clinical manifestations of inflammatory arthritis, focusing on sex differences and key signs which primary care clinicians should recognise. Methods: A narrative literature review was undertaken with regards to presentation of three commonly seen inflammatory arthritis conditions: Rheumatoid Arthritis, Psoriatic Arthritis and Axial Spondyloarthritis. Studies describing differences in presentation of these conditions between the sexes were selected for this descriptive analysis. Results: Overall, when compared to males, females endure a longer time to diagnosis, and experience increased disease activity, elevated levels of pain and poorer response to medication. Conclusions: Understanding the difference in presentation of inflammatory arthritis between sexes can accelerate diagnosis and improve treatment.

Rheumato doi: 10.3390/rheumato5030011

Authors: Jairo N. Fuertes Lauren Nandoo Michael T. Moore Prachi Anand Salini C. Kumar

Background/Objectives: Chronic medical conditions are comorbid with psychological disorders, often attributed to the weight of managing persistent demands associated with debilitating illness. Lifestyle adjustments, physical pain, and costs of health care can impose impairment of functioning, exacerbated by the onset of a chronic disease. While cause-and-effect directionality is difficult to ascertain, it is widely assumed that psychological stress can exacerbate the ability of patients to manage chronic medical conditions. Methods: The current study examined a novel model comprising five psychological factors which might explain variations in patients’ level of adherence, satisfaction, and quality of life. The sample consisted primarily of 124 low-income, female Hispanic patients, who were patients diagnosed with rheumatic and endocrine medical diagnoses. Results: Psychological distress and the lingering psychological effects of the COVID-19 pandemic were negatively associated with patient adherence, satisfaction, and quality of life, and that patients’ reports of the working alliances with their doctors moderated (i.e., significantly lessened) the negative association between the lingering impact of the COVID-19 pandemic and their satisfaction with care. Patients’ self-efficacy, resilience, and working alliance were all positively and significantly associated with adherence, satisfaction, and QOL. The association between working alliance and satisfaction represents a very large effect (r = 0.77, p < 0.001). Path analysis found a direct effect between psychological distress (stand. est. = 0.28, p = 0.05) and treatment adherence and a direct effect between COVID-19 impact and adherence (stand. est. = −0.19, p = 0.05). Conclusions: This study provides evidence of the role that both psychological stress and psychological strengths play in the experience of receiving medical care for low-income patients with rheumatic and endocrine conditions. Psychological stress inhibits adherence, and the physician–patient working alliance moderates the negative correlation between COVID impact and treatment satisfaction.

Rheumato doi: 10.3390/rheumato5030010

Authors: Freya Shah Siddharth Pravin Agrawal Darshilkumar Maheta Jatin Thukral Syeda Sayeed

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder with significant racial and ethnic disparities in prevalence, disease severity, and outcomes. Cardiovascular complications, including pericarditis, myocarditis, valvular disease, and conduction abnormalities, contribute to increased morbidity and mortality in SLE patients. This study examines racial and ethnic disparities in cardiovascular outcomes among hospitalized SLE patients in the United States. Methods: This retrospective study utilized the National Inpatient Sample (NIS) database from 2016 to 2021 to analyze hospitalizations of adult patients (≥18 years) with a primary or secondary diagnosis of SLE. Patients were stratified into racial/ethnic groups: White, Black, Hispanic, Asian, Native American, and Other. Primary outcomes include major adverse cardiovascular events (MACEs), which are a composite of in-hospital mortality, myocardial infarction (MI), sudden cardiac death, and other SLE-related outcomes including cardiac, pulmonary, and renal involvement. Statistical analyses included multivariable logistic regression models adjusted for demographic, socioeconomic, and hospital-related factors to assess racial disparities. Results: The study included 514,750 White, 321,395 Black, and 146,600 Hispanic patients, with smaller proportions of Asian, Native American, and Other racial groups. Black patients had significantly higher odds of in-hospital mortality (OR = 1.17, 95% CI = 1.08–1.26, p < 0.001) and sudden cardiac death (OR = 1.64, 95% CI = 1.46–1.85, p < 0.001) compared to White patients. Asian patients also exhibited increased mortality risk (OR = 1.37, 95% CI = 1.14–1.63, p = 0.001) as compared to Whites. Conversely, Black (OR = 0.90, 95% CI = 0.85–0.96, p = 0.01) and Hispanic (OR = 0.87, 95% CI = 0.80–0.96, p = 0.03) patients had lower odds of MI. Racial disparities in access to care, socioeconomic status, and comorbidity burden may contribute to these differences. Conclusion: Significant racial and ethnic disparities exist in cardiovascular outcomes among hospitalized SLE patients. Black and Asian individuals face higher in-hospital all-causes mortality and sudden cardiac death risks, while Black and Hispanic patients exhibit lower MI rates. Addressing social determinants of health, improving access to specialized care, and implementing targeted interventions may reduce disparities and improve outcomes in minority populations with SLE.

Rheumato doi: 10.3390/rheumato5030009

Authors: Sergio Rosini Gianantonio Saviola Stefano Rosini Eleonora Baldissarro Luigi Molfetta

Obesity, characterized by excessive or abnormal accumulation of body fat, is associated with a range of metabolic and inflammatory diseases, including osteoarthritis (OA). In obese individuals, adipose tissue expansion—via adipocyte hypertrophy or hyperplasia—is accompanied by altered secretion of adipokines such as leptin and adiponectin, which play significant roles in immune modulation, metabolism, and skeletal homeostasis. Leptin, acting through the hypothalamus, regulates the sympathetic nervous system and modulates hormonal axes, influencing bone metabolism and cartilage integrity. Elevated leptin concentrations in the synovial fluid, and the presence of its receptors on cartilage surfaces, suggest its direct role in cartilage degradation and OA progression. Conversely, adiponectin exerts anti-inflammatory effects, modulates osteoblast and macrophage activity, and appears to have a protective function in joint metabolism. These findings underscore the complex interplay between the adipose tissue, adipokines, and the osteochondral unit, highlighting the importance of their balance in maintaining joint health.

Rheumato doi: 10.3390/rheumato5030008

Authors: Nuno A. T. C. Fernandes Ana Arieira Betina Hinckel Filipe Samuel Silva Óscar Carvalho Ana Leal

Background/Objectives: This review analyzes the effects of invasive and non-invasive methods of knee joint unloading on knee loading, employing a biomechanical model to evaluate their impact. Methods: PubMed, Web of Science, Cochrane, and Scopus were searched up to 15 May 2024 to identify eligible clinical studies evaluating Joint Space Width, Cartilage Thickness, the Western Ontario and McMaster Universities Osteoarthritis Index, the Knee Injury and Osteoarthritis Outcome Score system, Gait velocity, Peak Knee Adduction Moment, time to return to sports and to work, ground reaction force, and the visual analogue scale pain score. A second search was conducted to select a biomechanical model that could be parametrized, including the modifications that each treatment would impose on the knee joint and was capable of estimate joint loading to compare the effectiveness of each method. Results: Analyzing 28 studies (1652 participants), including 16 randomized clinical trials, revealed significant improvements mainly when performing knee joint distraction surgery, increasing Joint Space Width even after removal, and high tibial osteotomy, which realigns the knee but does not reduce loading. Implantable shock absorbers are also an attractive option as they partially unload the knee but require further investigation. Non-invasive methods improve biomechanical indicators of knee joint loading; however, they lack quantitative analysis of cartilage volume or Joint Space Width. Conclusions: Current evidence indicates a clear advantage in knee joint unloading methods, emphasizing the importance of adapted therapy. However, more extensive research, particularly using non-invasive approaches, is required to further understand the underlying knee joint loading mechanisms and advance the state of the art.

Rheumato doi: 10.3390/rheumato5020007

Authors: Luis Angel Montero Furelos Clara Fernandez Peña Beatriz San Millan Tejedor

Statins are effective drugs for lowering cholesterol and reducing cardiovascular risk. Rarely, they can trigger autoimmune myopathies like immune-mediated necrotizing myopathy (IMNM), associated with anti-HMGCR antibodies. This condition may persist after statin discontinuation and requires immunosuppressive treatment. Despite these rare side effects, the benefits of statins outweigh the risks for most patients.

Rheumato doi: 10.3390/rheumato5020006

Authors: Tadashi Yasuda Satoshi Ota Sadaki Mitsuzawa Shinnosuke Yamashita Yoshihiro Tsukamoto Hisataka Takeuchi Eijiro Onishi

Objectives: This study aimed to compare hip abductor muscle composition and its age-related alterations between female patients with unilateral and bilateral osteoarthritis (OA) of the hip. Methods: This study enrolled 57 and 43 female patients with unilateral and bilateral advanced OA, respectively. Muscle composition of the glutei medius and minimus and the upper portion of the gluteus maximus was evaluated by computed tomography for planning unilateral total hip arthroplasty. The cross-sectional area ratio of the individual composition to the total muscle was calculated. Correlation coefficients were calculated to determine associations between age and muscle composition variables. Results: Comparison of hip abductor muscle composition between the affected and the contralateral sides in unilateral OA patients showed increased fatty infiltration in the muscles around the affected joint. Comparison of the composition around bilateral OA between the joint scheduled for operation and the contralateral joint demonstrated enhanced fatty infiltration in the glutei medius and minimus but no increase in the gluteus maximus around the operation-scheduled joint. Comparison of muscle composition between unilateral and bilateral OA demonstrated similar fatty infiltration around the operation-scheduled joint whereas there was increased fatty infiltration around the contralateral joint of bilateral OA. Significant association was found between age and hip abductor muscle composition around both sides of unilateral OA. However, there was no association between age and hip abductor muscle composition around both sides of bilateral OA. Conclusions: There were significant differences in hip abductor muscle composition and its age-related alterations between female patients with unilateral and bilateral OA.

Rheumato doi: 10.3390/rheumato5020005

Authors: Katarina Kovač Ivan Ljudevit Caktaš Nataša Kalebota Porin Perić

Hemophilia is an X-linked genetic disorder that predominantly affects males, with females typically serving as asymptomatic carriers. Hemophilia A results from a deficiency or dysfunction of coagulation factor VIII, while a deficiency in factor IX causes hemophilia B. A less common condition, factor XI deficiency (formerly hemophilia C), is categorized as a rare bleeding disorder. The severity of hemophilia is classified based on the activity concentration of factors VIII and IX: severe (<1 IU/dL), moderate (1–5 IU/dL), and mild (6–<40 IU/dL). One of the most prevalent complications of hemophilia is hemarthrosis, bleeding into joint cavities, which, if unrecognized or untreated, can lead to hemophilic arthropathy. The pathophysiology of hemophilic arthropathy involves two key mechanisms: the accumulation of iron from blood in synovial joints, which cannot be cleared due to repeated bleeding, and the inflammatory response, resulting in synovial hyperplasia and the progressive destruction of cartilage and bone. Hemophilic arthropathy significantly impairs quality of life, causing chronic pain, joint deformities, and sometimes requiring surgical intervention. This thesis will examine the pathophysiology and management strategies for hemophilic arthropathy.

Rheumato doi: 10.3390/rheumato5020004

Authors: Celia María López-Jiménez Francisco Javier Cano-García Susana Sanduvete-Chaves Salvador Chacón-Moscoso

Background: Although the Profile of Mood States has been proposed by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) to measure emotional functioning in chronic pain patients, it has not yet been validated in these patients. Objective: To confirm the factor structure and internal consistency of the Shortened Version of the Profile of Mood States (37 items) in patients with chronic pain. Methods: A confirmatory factor analysis (CFA) was conducted to test the theoretical structure of six factors that result in a Total Mood Disturbance episode: Tension–Anxiety (six items), Depression–Dejection (eight items), Anger–Hostility (seven items), Vigor–Activity (six items), Fatigue–Inertia (five items), and Confusion–Bewilderment (five items). Participants: A total of 588 patients with chronic pain from Spanish primary care health and community centers completed the questionnaire. Results: The factors presented adequate reliability coefficients, McDonald’s Omega (ω) between 0.77 and 0.91, and appropriate average discrimination indexes (D), ranging from 0.35 to 0.67. The Total Mood Disturbance yielded excellent results, ω = 0.95, D = 0.61. The original structure was confirmed, ECVI = 4.361 (saturated ECVI = 2.395; independent ECVI = 21.855); RMSEA = 0.070, 90% CI [0.067, 0.072]; GFI = 0.974; AGFI = 0.971; CFI = 0.853; NFI = 0.812; and NNFI = 0.843. Conclusions: The Shortened Version of the Profile of Mood States has been proven to be a valid and reliable measure of emotional functioning in chronic pain patients.

Rheumato doi: 10.3390/rheumato5010003

Authors: Dimitrina Miteva Konstantina Bakopoulou Ivan Padjen Issa El Kaouri Latchezar Tomov Georgi V. Vasilev Russka Shumnalieva Tsvetelina Velikova

Rheumatoid arthritis (RA) is an immune-mediated chronic and long-term condition that can lead to severe joint damage and disability. It has been shown that doctor–patient interaction and communication can have a significant impact on faster patient diagnosis and treatment outcomes. Primary care (PC) is the first level of patient contact with doctors and the health system. Communication between them is often ineffective, leading to delays in diagnosis, care, and the use of disease-modifying antirheumatic drugs (DMARDs). The protocols and standards for the treatment of RA are well established by all rheumatology organizations. All of them recommend early initiation of DMARDs, which leads to better long-term outcomes. There are some recommendations that would lead to better optimization of recognition, management, and referral practices. Early diagnosis, effective communication between general practitioners and specialists, and patient education about possible targeted therapies and biological products, as well as subsequent monitoring of therapies and screening for risk factors and comorbidities, will improve patient health and optimize costs. We aimed to offer strategies and possibilities for integrating and optimizing primary care and specialized therapies in RA because proper management will reduce the severity of the disease and even reduce mortality from chronic diseases such as RA.

Rheumato doi: 10.3390/rheumato5010002

Authors: Bruce Rothschild

Muscle function and pathology are complex subjects; the medical fields involved in their diagnosis and treatment represent rheumatology, physiatry and metabolic disease, among others. While we, rheumatologists, concentrate our efforts predominantly on inflammatory varieties and those associated with medications (e.g., corticosteroid and statin use), we are often the “turn to” gatekeepers for the identification of the diagnostic category represented by a patient’s symptomatology. The broad base of rheumatologic training prepares us for the recognition of endocrinologically derived myopathy. This subject and fundamentally biochemically derived myopathies form the basis for this review.

Rheumato doi: 10.3390/rheumato5010001

Authors: Anna M. Timofeeva Nataliya A. Klyaus Sergey E. Sedykh Georgy A. Nevinsky

The SARS-CoV-2 virus can cause hyperstimulation of the immune system, sometimes leading to the production of various autoantibodies and increased levels of interferons and interleukins in blood plasma. Background/Objectives: Only a few studies are currently focusing on the dynamics of immunological indices after any transferred infectious disease encountered by an organism for the first time. The attention of researchers and clinicians is captured by the dynamics of antibody titers and immunologic markers (interferons and interleukins), as well as the correlation of immunologic indices with changes in the symptomatology of long COVID. This paper discusses the association of antibodies against various autoantigens with rheumatological and neurological manifestations of COVID-19. Our study patient was a 36-year-old man diagnosed with polyneuropathy, which developed after COVID-19. We conducted a dynamic follow-up of the patient for two years. Methods: The blood plasma samples collected were analyzed by ELISA for different autoantigens, IFN-γ, and a variety of interleukins. Results: An association between rheumatologic and neurologic markers in patients with long COVID symptoms was considered. Antibody titers for myelin basic protein (MBP), double-stranded DNA (dsDNA), single-stranded DNA (dsDNA), and IFN-γ, IL-1, IL-6, and IL-10 levels significantly increased during the posthospital period when the patient reported persistent symptoms of long COVID, with complaints decreasing after the symptoms were resolved. Conclusions: The findings of this study shed light on the dynamic alterations of immunological factors, and elucidate the mechanism by which SARS-CoV-2 infection disrupts immunotolerance and eventually restores equilibrium, leading to the rheumatological pathology. Significantly, the notable rise in antibody titers for various autoantigens was transient and did not lead to the progression of autoimmune pathology.

Rheumato doi: 10.3390/rheumato4040017

Authors: Dominika Blachut Brygida Przywara-Chowaniec Andrzej Tomasik

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease with a complex pathogenesis, primarily affecting women. SLE is associated with the presence of autoantibodies, chronic inflammation, and multi-organ dysfunction. Increasing evidence suggests that SLE is linked to a higher risk of malignancies, compared to the general population, though the mechanism behind this phenomenon remains unclear. Malignant tumors are the fourth most common cause of death in SLE patients. SLE is associated with an elevated risk of hematological cancers, as well as cancers of the lungs, thyroid, liver, and bile ducts. The aim of this paper is to review the latest literature on the pathogenesis, epidemiology, and risk factors for malignancies in SLE patients. The mechanisms of oncogenesis in SLE are still not fully understood, and the pathophysiology includes such risk factors as chronic inflammation, immune disorders, therapies used, overlap syndromes of connective tissue diseases, viral infections, and traditional cancer risk factors. Evaluating these factors and understanding the process of oncogenesis are crucial for prevention. Systemic lupus erythematosus may be an independent risk factor for the development of malignancies. It is important to raise awareness among SLE patients about the increased risk of malignancies. Further research is needed to establish guidelines for prevention, including screening recommendations.

Rheumato doi: 10.3390/rheumato4040016

Authors: Kenneth P. H. Pritzker Arash Samari

Early diagnosis and therapy in axial spondyloarthritis, axSpA, is known to reduce long-term morbidity. However, the time from symptom onset to diagnosis is typically delayed by several years, and this situation has not improved in recent years despite greater clinical awareness and better imaging. This narrative review discusses the underlying causes for axSpA diagnostic delay. It is proposed that to reduce axSpA diagnostic delay, a better understanding of the axSpA subclinical inflammatory process is required, together with machine learning-enabled inflammation/repair biomarkers such as lipocalin 2 and lipocalin 2-matrix metalloprotease 9, developed through extensive clinical domain knowledge.

Rheumato doi: 10.3390/rheumato4040015

Authors: Amelia Carmela Damasco Roberta Ramonda Giacomo Cozzi Mariagrazia Lorenzin Paolo Sfriso Francesca Oliviero Chiara Baggio

Background: Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy characterized by a variety of clinical manifestations, mainly affecting joints and entheses, but also skin, nails, the eye, and the intestine. Objectives: In this review, we describe the essential characteristics of both synovial membranes and synovial fluid (SF) in PsA. Similarly to other inflammatory arthritis, the histological peculiarities in PsA synovitis are lining hyperplasia, neoangiogenesis, and sublining infiltration by immune cells and inflammatory mediators. Synovial effusions are frequent in PsA patients and SF analysis allows us to determine the pathological process occurring in the joint. Routine examinations help clinicians in defining the inflammatory status and possibly the detection of specific cell subsets. In addition, pathogenic crystals including monosodium urate and calcium pyrophosphate may be found in PsA SF. Conclusions: SF represents a potential substrate to identify the biomarkers that are useful to predict disease progression and response to medications in PsA patients, thus guiding the choice of appropriate and tailored pharmacological treatment.

Rheumato doi: 10.3390/rheumato4040014

Authors: Azmath Mubeen Uma N. Dulhare

Background/Objectives: Accurate detection and classification of nodules in medical images, particularly rheumatoid nodules, are critical due to the varying nature of these nodules, where their specific type is often unknown before analysis. This study addresses the challenges of multi-class prediction in nodule detection, with a specific focus on rheumatoid nodules, by employing a comprehensive approach to feature extraction and classification. We utilized a diverse dataset of nodules, including rheumatoid nodules sourced from the DermNet dataset and local rheumatologists. Method: This study integrates 62 features, combining traditional image characteristics with advanced graph-based features derived from a superpixel graph constructed through Delaunay triangulation. The key steps include image preprocessing with anisotropic diffusion and Retinex enhancement, superpixel segmentation using SLIC, and graph-based feature extraction. Texture analysis was performed using Gray-Level Co-occurrence Matrix (GLCM) metrics, while shape analysis was conducted with Fourier descriptors. Vascular pattern recognition, crucial for identifying rheumatoid nodules, was enhanced using the Frangi filter. A Hybrid CNN–Transformer model was employed for feature fusion, and feature selection and hyperparameter tuning were optimized using Gray Wolf Optimization (GWO) and Particle Swarm Optimization (PSO). Feature importance was assessed using SHAP values. Results: The proposed methodology achieved an accuracy of 85%, with a precision of 0.85, a recall of 0.89, and an F1 measure of 0.87, demonstrating the effectiveness of the approach in detecting and classifying rheumatoid nodules in both binary and multi-class classification scenarios. Conclusions: This study presents a robust tool for the detection and classification of nodules, particularly rheumatoid nodules, in medical imaging, offering significant potential for improving diagnostic accuracy and aiding in the early identification of rheumatoid conditions.

Rheumato doi: 10.3390/rheumato4040013

Authors: Caya M. McFalls Lianne M. Connolly Alfred G. Fustakgi Carol M. Artlett

Background: Interleukin-11 (IL-11) is increased in patients with systemic sclerosis (SSc) and is thought to play a role in fibrosis. Many studies have reported decreased fibrosis when IL-11 is blocked, but few have examined factors that induce IL-11 expression. Because fibrosis has been linked to activated inflammasomes driving caspase-1 maturation and the secretion of IL-1β, we set out to determine if IL-11 expression was dependent on caspase-1 activity. Methods: Primary lung fibroblast cell lines derived from patients with SSc, IPF (fibrotic control), and healthy individuals were cultured at low passage. Gene expression for IL-11 and the IL-11 receptor (IL-11Rα1) was analyzed using qPCR and normalized to the control, and collagen production was measured using Sirius Red. Results: SSc and IPF fibroblasts expressed significantly more IL-11 transcripts than normal cells (3.35-fold and 9.97-fold more, p = 0.0396 and p = 0.0023, respectively). IL-11Rα1 was expressed 2.32-fold and 2.27-fold more in SSc and IPF (p = 0.0004 and p = 0.0032, respectively) than in normal cells. In SSc fibroblasts, inhibition of caspase-1 with YVAD decreased IL-11 expression by 49.59% (p = 0.0016) but did not affect IL-11Rα1 expression (p > 0.05). IL-11 expression was increased 2.97-fold with TGF-β1 (p = 0.0030) and 22.24-fold with IL-1β (p < 0.0001), while the expression of IL-11Rα1 was not induced with these two cytokines. LPS increased IL-11 expression in normal fibroblasts 1.52-fold (p = 0.0042), which was abolished with YVAD (p < 0.0001). IL-11Rα1 gene transcripts were also increased with LPS 1.50-fold (p = 0.0132), but YVAD did not inhibit this expression. In these studies, we were unable to detect IL-11 protein nor were we able to induce COL1A1 expression or increase the total amount of collagen secreted by fibroblasts with human recombinant IL-11. Conclusions: IL-11 and its receptor, IL-11Rα1, are both elevated in fibrosis. IL-11 expression is dependent on inflammasome activation of caspase-1 and the downstream cytokines TGF-β1 and IL-1β, while IL-11Rα1 was only dependent on NF-kB.

Rheumato doi: 10.3390/rheumato4030012

Authors: Jennifer Behbodikhah Lisa Balistreri Steven E. Carsons

Sjogren’s Disease (SjD) is associated with an increased risk of lymphoma. We investigated the prevalence of lymphoma in a retrospective case series of patients with SjD and reported on the clinical presentation, treatment, response, and outcome. A retrospective review of 132 patients diagnosed with Sjogren’s Disease was conducted at our institution from June 2000 to November 2023, and 10 cases of malignant lymphoma were identified. Clinical and biological markers known to be predictors of lymphoma, as well as lymphoma characteristics, were examined. The most common predictive lab findings were hypergammaglobulinemia, the rheumatoid factor, and lymphopenia. Persistent parotid gland enlargement was also found in greater than 50% of patients. The majority of patients were Caucasian females, and the average time between the diagnosis of SjD and lymphoma was 14.3 years. The median age at lymphoma diagnosis was 59.5 years, with 9 out of 10 lymphomas identified as non-Hodgkin lymphoma, the majority of cases being mucosa-associated lymphoid tissue (MALT) lymphoma. We identified similarities in our series, such as laboratory markers and clinical symptoms, to those previously identified as possible predictors of lymphoma development. These factors may be useful in determining the risk of malignancy development and justify the need for long-term monitoring, as well as provider education and awareness.

Rheumato doi: 10.3390/rheumato4030011

Authors: Bruce Rothschild

Fibromyalgia might be considered as the body’s response to the slings and arrows of outrageous fortune [...]

Rheumato doi: 10.3390/rheumato4030010

Authors: Nira Ferdous Johannes J. Rasker Shabnam Akhter Md. Kamruzzaman Md. Nazrul Islam

Irritable bowel syndrome (IBS) is common in ankylosing spondylitis (AS) and may be associated with the disease. We aimed to determine the prevalence of IBS in AS patients and its association with clinical and demographic patient characteristics and with macroscopic and microscopic gut lesions. Sixty consecutive AS patients were included in this study. Disease activity was assessed with the BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and functional status with the BASFI (Bath Ankylosing Spondylitis Functional Index). The ROME III criteria were used to diagnose IBS. Macroscopic lesions were graded during colonoscopies. Biopsy specimens were taken from the terminal ileum, colon (ascending, transverse and descending) and rectum. Histological samples were scored with Cuvelier grading. The prevalence of IBS was 23.3% (14/60). The mean age of 14 IBS subjects (10 male) was 32 ± 8.50., with a higher BASDAI (p = 0.046). Macroscopic lesions were more frequent in IBS cases in the terminal ileum (46.2% vs. 34.9%), ascending colon (21.4% vs. 2.2%) and rectum (21.4% vs. 17.4%), with Grade 2 significantly more prevalent in the ascending colon (p = 0.03). Microscopic lesions did not differ among the IBS-present and -absent groups. In conclusion, the prevalence of IBS was high in AS patients and associated with higher disease activity. Grade 2 macroscopic lesions were more frequent in the ascending colon.

Rheumato doi: 10.3390/rheumato4030009

Authors: Tsvetelina Velikova Dimitrina Miteva Maria Kokudeva Georgi H. Vasilev Simeon Monov Russka Shumnalieva

Systemic lupus erythematosus (SLE) is a chronic, autoimmune, immune complex-mediated disease affecting mainly females at a young age. The disease etiology is still unknown, and different genetic and epigenetic factors related to disease onset and manifestations are being explored. The standard treatment regimen for SLE includes the long-term use of corticosteroids and non-specific immunosuppressive agents, often limited by co-morbidities or related side effects. However, recent advances in disease pathogenesis clarifying the role of inflammatory cytokines, chemokines, immune cells, and co-stimulation molecules have made a more practical, targeted approach possible, leading to personalized treatment strategies. This review summarizes current knowledge about SLE-targeted therapies in clinical practice.

Rheumato doi: 10.3390/rheumato4020008

Authors: Rebecca Michelle Bingham-Byrne Esra Ozdenerol

Lyme disease is a zoonotic infectious disease. Increased public interest in Lyme disease has caused increased efforts by researchers for its surveillance and control. The main concept for this paper is to determine the mammalian species composition of areas at high risk for Lyme disease utilizing GIS-based (Geographic Information Systems) techniques coupled with k-means clustering, random forest, and multinomial logistic regression. Cluster analysis results were similar to previous work involving maps that display areas where people are at high risk for developing Lyme disease. There were differences in which mammal species presence had associations with Lyme disease risk observed at the two different scales within this analysis, with some overlap observed between the national scale and the smaller regions, as well as some overlap between the Rocky Mountain and Southeast regions that was not found at the national scale. This is an investigative analysis to determine which species are needed for habitat suitability analyses in efforts to prioritize vaccine deployment locations. There has been limited research on vaccine deployment for Lyme disease. Increasing our understanding of not only the vaccine but also the interactions between the components of disease transmission is necessary to control this infectious disease successfully.

Rheumato doi: 10.3390/rheumato4020007

Authors: Bruce Rothschild

The spectrum of disorders/phenomena encompassed in the practice of rheumatology is quite broad. In addition, our expertise is typically sought whenever other physicians encounter phenomena outside their knowledge base. While skin alterations typically prompt referrals to dermatology practices, alterations underlying the skin (e.g., subcutaneous) may well represent localization in “no man’s land” or an orphaned localization, with rheumatology thus referred as to the specialty of last resort—one of the roles that rheumatology has fulfilled for more than half a century. The current review addresses the cacophony of disorders producing or associated with variouslysized subcutaneous nodules. Their classifications, while necessarily artificial, encompass the full spectrum of pathologic processes. They are delineated in the current style to facilitate the consideration required to distinguish among them and to facilitate recognize the underlying processes for which we as rheumatologists are renowned.

Rheumato doi: 10.3390/rheumato4020006

Authors: Joana J. da Costa Lisa Christ Peter M. Villiger Monique Vogel Martin F. Bachmann

This work aimed to investigate a potential link between serum IL-1β levels in patients with giant cell arteritis (GCA) and their responsiveness to combined anti-IL-6 receptor (IL-6R) and glucocorticoid (GC) treatments within the context of two separate clinical trials. IL-1β levels were analyzed in serum samples of two prospective clinical trials investigating tocilizumab in GCA patients using quantitative Polymerase Chain Reaction (qPCR) based Proximity Ligation Assays (PLA). In the phase II randomized controlled trial, serum samples from five patients were quantified at two critical time points: the commencement of the trial (Week 2) and the conclusion of the trial (Week 52). In the GUSTO trial, serum samples from nine patients were similarly analyzed using PLA at Day 0 and Week 52. Furthermore, for the GUSTO trial, serum samples from 18 patients were assessed for IL-1β and IL-1RN at six time points: days 0, 3, and 10, weeks 4, 24, and 52 by a second assay (Proximity Extension Assay, PEA). PLA results from both studies indicated that IL-1β levels were below 1 pg/mL in most of the patients, resulting in notable signal deviations within the same samples. In the analysis of the GUSTO trial, both PLA and PEA exhibited similar trends in IL-1β variations among patients from day 0 to week 52. Notably, the PEA analysis did not show significant variation over time. Furthermore, we did not find a correlation of IL-1β levels with active disease as compared to remission, but interestingly, the measurement of IL-1β receptor antagonist (IL-1RN) revealed a substantial decrease over time. Our study shows that IL-1RN but not IL-1β concentration in serum samples could be directly related to anti-IL-6R treatment in patients diagnosed with GCA.

Rheumato doi: 10.3390/rheumato4010005

Authors: Fares Saliba Omar Mourad Jonathan Mina Fadi Haddadin Laurence Aoun Shaza Almardini Saif Abu-baker Koushik Sangaraju Gaetano Di Pietro Daniel Gaballa Suzanne El-sayegh

Gout is highly prevalent in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD), owing to impaired uric acid excretion. However, treating gout in this population is challenging due to concerns about medication safety and efficacy with reduced kidney function. This review examines the evidence of various pharmacologic and non-pharmacologic approaches to managing gout in CKD/ESRD. For acute gout flares, there is insufficient evidence to guide optimal dosing of NSAIDs, colchicine, and corticosteroids in advanced CKD. The risks generally outweigh the benefits of NSAIDs and colchicine. Corticosteroids appear safer but require individual risk-benefit assessments. Interleukin-1 inhibitors show promise, but larger studies are needed. For long-term urate lowering, xanthine oxidase inhibitors like allopurinol and febuxostat are preferred over probenecid and other uricosurics. However, studies specifically evaluating urate-lowering therapies in CKD are scarce, resulting in conflicting expert guidelines. Starting with low allopurinol doses and gradual titration can mitigate the risks. Higher allopurinol doses may be needed to reach urate targets in some CKD patients. Febuxostat’s safety in advanced CKD remains debated. Optimal gout management in dialysis patients is also unclear, including when to continue urate-lowering therapy. Overall, gout is often suboptimally treated in CKD/ESRD, highlighting the need for more research to guide therapy in this population. Improving management can significantly reduce the burden of these comorbid diseases.

Rheumato doi: 10.3390/rheumato4010004

Authors: Sambhawana Bhandari Lisa Zickuhr Maun Ranjan Baral Sanjeev Bhalla Heather Jones Robert Bucelli Deepali Sen

Anti-melanoma differentiation-associated gene 5 (MDA-5) dermatomyositis (DM) is noteworthy for its association with rapidly progressive interstitial lung disease (RP-ILD), vasculopathy, and distinctive cutaneous features. First identified in a Japanese cohort in 2005, MDA-5 DM carries a significant mortality risk, emphasizing the crucial need for early diagnosis. This review explores the pathogenesis, clinical presentation, diagnosis, management, and prognosis of MDA-5 DM and ILD and includes new research and recommendations regarding disease management.

Rheumato doi: 10.3390/rheumato4010003

Authors: Md. Nazrul Islam S M Ahamed Abed Shirin Tarafder Abul Khair Ahmedullah Johannes J. Rasker Md. Injamul Haq Methun

Objectives: The aim of this study was to investigate whether serum TNF-α and IL-1β levels are independent risk factors for depression in axSpA patients. Methods: All axSpA patients with BASDAI ≥4 were invited consecutively between March 2021 and August 2021 to participate. Depression was evaluated with the WHO-5 Well-Being scale. Disease activity was assessed using BASDAI (0–10), ASDAS-CRP (0.61–7.22), ASDAS-ESR (0.29–7.61), and health status by ASAS-HI (0–17). Serum TNF-α and IL-1β levels were measured by ELISA. An association between depression and cytokine levels was investigated with Spearman’s rank correlation coefficient test. Results: A total of 252 axSpA patients (155 men) could be included; of these, 123 (48.81%) were depressed, and of these, 75 were male. Serum TNF-α and IL-1β were not significantly associated with depression (r −0.041 and 0.110, respectively). Serum TNF-α levels were higher in depressed female axSpA patients (20.05 vs. 17.87; p = 0.03). Differences between depressed and non-depressed patients were respectively: TNF-α (19.7 vs.18.0; p= 0.84), IL-1β (32.3 vs. 21.2; p= 0.04), BASDAI (5.47 vs. 4.77; p = 0.000), ASDAS-CRP (4.17 vs. 3.78; p = 0.000), ASDAS-ESR (3.86 vs. 3.39; p = 0.000), CRP (48.43 vs. 37.93 mg/L; p = 0.000), and ASAS-HI (13.37 vs. 10.24; p = 0.000). Factors associated with depression were: peripheral joint involvement (OR = 1.073, 95% CI 1.012–1.138), BASDAI (OR = 1.534, 95% CI 1.011–2.335), and ASAS-HI (OR = 1.39, 95% CI 1.239–1.557). Only in depressed patients with peripheral SPA were higher IL-1β levels found, though the differences were probably not clinically relevant. Conclusions: Serum TNF-α and IL-1β were not independently related to depression in axSpA patients. Disease activity, peripheral joint involvement, and reduced health status showed the highest association with depression.

Rheumato doi: 10.3390/rheumato4010002

Authors: Bruce M. Rothschild

This journal for Rheumato(philes) has provided a vehicle for the interdisciplinary sharing of the challenges and interventions of our specialty. The provision of state-of-the-art information is not at the expense of the basics from which it has grown. From its initial status as a source of discomfort, a review of back pain diagnostics and therapeutics provides a background for facilitating contemporary practice. We have met the enemy in the form of COVID-19, addressing its many rheumatologic complications, and have been introduced to the vagaries of IgG4 disease. Our clinical skills are tested in recognition of primary hypertrophic osteoarthropathy. The relationship of dental health to rheumatoid arthritis and nutritional issues is currently undergoing scientific review. A unique feature, one we seldom seem to discuss, is the evaluation of disease manifestations when the customary tools are not available. The latter brings us full circle in the evolution of our field. When our colleagues found diagnostic or treatment approaches elusive, they did not call for Ghostbusters; they called for us.

Rheumato doi: 10.3390/rheumato4010001

Authors: Giovanni Maria Rossi Chiara Pala Davide Gianfreda

Fibroinflammatory diseases are a group of rare pathologies in which the hallmark is the exuberant deposition of fibrotic tissue and inflammatory cellular infiltrates, characteristic of the specific disease. A sclerotic mass develops within soft tissues and/or organs, damaging and replacing them, with effects ranging from asymptomatic to life-threatening clinical manifestations. The kidneys and urinary tract can be involved in some of these diseases, which can lead to acute kidney injury, chronic kidney disease, and even end-stage kidney disease. IgG4-related disease, retroperitoneal fibrosis, and Erdheim–Chester disease are the three fibroinflammatory disorders that can involve the kidneys. Only a timely and accurate collection of clinical, radiological, metabolic, laboratory, and histological data allows prompt diagnosis and targeted treatment of these pathologies, allowing the stoppage of the evolution of renal and systemic manifestations, which can lead to complete remission. The epidemiology, clinical and histological features, and management of these conditions are herein described in a narrative fashion.

Rheumato doi: 10.3390/rheumato3040017

Authors: Ren Martin Rachael Taylor Clive Kelly

We experience life and interact with others in a multitude of ways. The term ‘neurodivergence’ refers to variations from what is considered typical or normal. Neurodivergence influences an individual’s behaviour in social situations and is associated with atypical emotional responses. This can precipitate inequity and rejection. Neurodivergent females are especially prone to many physical and psychological health issues, and musculoskeletal disorders account for a significant proportion of these. Research and education into neurodivergent conditions in females should inform the reassessment of clinicians’ present approach to those who present with multiple unexplained symptoms. Obtaining official confirmation of a neurodivergent condition improves access to support services and helps them and their family better understand themselves and the challenges they face. This commentary highlights the increased risk of developing rheumatological disease for females with neurodivergent conditions and suggests how clinicians might increase their awareness of this.

Rheumato doi: 10.3390/rheumato3040016

Authors: Bruce Rothschild

The axial skeleton, with the exception of spondyloarthropathy, is the most neglected aspect of rheumatology training and, as a result, perhaps the most complex. The clinical “problem” of back/neck pain could be considered the “orphan child” of medicine, and our perspective as rheumatologists is often sought for such entities. Sources of back/neck pain are myriad, and not all phenomena affecting the back are symptomatic. Perhaps the one that has most concerned rheumatologists is the cervical instability associated with rheumatoid arthritis. The current review examines intrinsic and extrinsic alterations in axial skeletal components, providing a guide to discriminating the causes (e.g., Scheuermann’s disease versus osteoporotic compression and the various forms of axial joint ankylosis) and the implications of vertebral endplate alterations. The specificity and sensitivity (limitations) of radiologic findings are reviewed, with a reminder that vertebral body osteophytes do not represent osteoarthritis and are therefore unlikely to explain back or neck complaints and that it is our clinical examination which will likely suggest symptom origin.

Rheumato doi: 10.3390/rheumato3040015

Authors: Elena Corinaldesi Marianna Fabi Ilaria Scalabrini Elena Rita Praticò Laura Andreozzi Francesco Torcetta Marcello Lanari

Kawasaki disease (KD) is an acute vasculitis that mainly affects children under 5 years of age, leading to coronary artery alterations (CAAs) in 25% of untreated patients. Macrophage activation syndrome (MAS) is a secondary hemophagocytic lymphohistiocytosis (HLH) that can complicate the acute, subacute, and chronic phases of KD. We retrospectively reviewed three cases of children affected by KD complicated with MAS hospitalized in two pediatric units in Emilia Romagna, a northern region of Italy. Case 1: a previously healthy 23-month-old female with full clinical criteria of KD and a hemorrhagic rash due to MAS during the acute phase of the illness. This patient responded promptly to a high dose of intravenous immune globulin (IVIG) and three pulses of high doses of methylprednisolone (MPD) with improvement in clinical signs and laboratory tests without the development of CAA at any phase of illness. Case 2: a previously healthy 10-month-old female with incomplete KD with persistent fever and maculopapular rash. This patient did not respond to IVIG and developed MAS during the subacute phase, characterized by persistent fever, hypertransaminasemia, hyperferritinemia, and hypofibrinogenemia after two high doses of IVIG and boluses of MPD. The patient responded to the addition of IL-1 blocker and anakinra and did not present CAA alterations during any phase of the illness. Case 3: a previously healthy 26-month-old male with incomplete KD with fever, maculopapular rash, cheilitis, and hyperemic conjunctivitis. This patient developed gallbladder hydrops and CAA in the acute phase and did not respond to two high doses of IVIG and a high dose of MPD. In the subacute phase, this patient was complicated with MAS and responded to intravenous anakinra. During the subacute phase, the patient developed transient aneurysms that regressed during the chronic phase. These cases reiterate that prompt diagnosis and aggressive immunomodulatory treatment can limit the most severe complications of MAS complicating KD. High doses of IVIG and MPD may result in a favorable outcome or more aggressive adjunctive treatment may be needed. Anakinra, cyclosporine, monoclonal antibodies, and plasmapheresis can be used as adjunctive treatment in the case of unresponsive MAS in KD. Notably, MAS, present during the subacute phase in cases 2 and 3, promptly responded to anakinra, an IL-1 blocker, without the use of cyclosporine. Our experience confirms that the IL-1 blocker can be considered an optimal choice after non-response to IVIG and MPD in KD complicating with MAS, avoiding over-treatment with cytotoxic drugs.

Rheumato doi: 10.3390/rheumato3030014

Authors: Lorenzo Moretti Davide Bizzoca Andrea Michele Abbaticchio Alessandro Geronimo Giuseppe Solarino Biagio Moretti

Lipoma arborescens (LA) is a rare benign soft tissue tumor characterised by a hyperproliferation of villi and fat cells in the joint synovium. It is most frequently localized in the knee as reported here. This is a case report of a 16-year-old adolescent, affected by type I diabetes mellitus, who reported left knee pain and functional limitation to medical attention. She performed a physical examination, MRI and biopsy using an arthroscopic approach, leading to the LA diagnosis and classification. The LA has been thus treated with an arthroscopic synovectomy, which is the treatment of choice for LA, characterized by a low recurrence rate.

Rheumato doi: 10.3390/rheumato3030013

Authors: Fernando Madero López Lucinda Velázquez Alonso Daniel Clemente Garulo Juan Carlos López Robledillo

Chronic pain is the most common symptom of osteoarthritis and is very often accompanied by limitations in the performance of activities of daily living and has a negative impact on patients’ quality of life. It is estimated that 14% of the elderly population routinely use NSAIDs for pain management, not without serious adverse effects. Objective: We aimed to test the efficacy and possible side effects of OliminaDol (encapsulated combination of purified hydroxytyrosol, omega-3 fatty acids and curcumin) in the treatment of chronic osteoarthritis pain. Seventy-four patients with a diagnosis of osteoarthritis who had chronic pain were selected. The therapeutic intervention consisted of self-administering one capsule of the supplement every 12 h for 30 days. A visual analogue scale (VAS) was used for pain assessment. The efficacy was assessed by comparing the means of pain intensity at baseline and at the end of treatment. The data on the National Cancer Institute (NCI-CTCAE) version 4 criteria were also analyzed. Results: Thirty-six patients were evaluable for the primary objective. The mean value + standard deviation of pain intensity measured by the VAS scale at day +1 was 5.78 + 0.15 and the mean value of pain 30 days after initiation of treatment was 4.19 + 0.22. There was a decrease in pain intensity of 1.63 + 2.28 with p = 0.000. A total of 27 patients (75%) had pain reduction and in 19 of them (52.7%), the difference was greater than 2 points on the VAS scale. OliminaDOL administration was associated with very few and insignificant side effects, notably constipation in two patients (5.4%) and a fishy taste in three patients (8.1%). Conclusions: The administration of OliminaDOL produced a significant decrease in the mean value of pain intensity without side effects. These results, together with other published studies, demonstrate the possibility that some supplements, or a combination of them as in our case, can be an alternative for the treatment of chronic pain.

Rheumato doi: 10.3390/rheumato3030012

Authors: Nermeen Hassan A. Moneim Mennatullah A. Hemed Peter M. ten Klooster Johannes J. Rasker Nashwa K. El Shaarawy

This study aims to compare the effect of corticosteroid injection (CSI) followed by therapeutic ultrasound (TUS) with that of extracorporeal shock wave therapy (ESWT) in patients with chronic plantar fasciitis (PF) and to explore the impact of a sedentary lifestyle and obesity on treatment outcomes. Female patients with PF were randomly allocated to receive ESWT (group A, n = 25) or CSI + TUS (group B, n = 25). Interventions: Group A received four once-weekly sessions of ESWT (2000 shocks, 2.5 bar pressure, 10.0 Hz frequency). Group B received a local injection of 40 mg triamcinolone acetonide with 2 mL 1% xylocaine, followed by three sessions of TUS per week for two weeks. Pain visual analog scale (VAS pain), plantar fasciitis pain and disability scale (PFPDS), and fascia thickness using musculoskeletal ultrasound were all measured at baseline, 4 weeks, and 12 weeks after the end of treatment. VAS pain and PFPDS improved significantly in both groups after 4 and 12 weeks. In the ESWT group, the pain improved significantly more at 12 weeks (p = 0.004). In obese patients (BMI > 29.9 kg/m2), ESWT gave more long-term pain relief at 12 weeks follow-up. In both the ESWT and CSI + TUS groups, after 12 weeks, the VAS pain improved more in patients with a sedentary daily life than in those with active life (p = 0.021 and p = 0.014, resp.), as well as the PFPDS (p = 0.014 and p = 0.019, resp.). Plantar fascia thickness decreased in both groups at 12 weeks. In both groups, improvements in function (PFPDS) correlated significantly with decreased plantar fascia thickness at 4 and 12 weeks. In the CSI + TUS group only, the decrease in plantar fascia thickness was correlated with pain improvement at both follow-up visits. Echogenicity changed from hypoechoic to iso- or hyperechoic and improved significantly in both groups at 12 weeks follow-up, but changes were not different between the groups (p = 0.208). Both CSI + TUS and ESWT are effective treatments for female patients with chronic plantar fasciitis resulting in pain relief and improved function and fascia thickness. ESWT gave more pain relief at 12 weeks follow-up. CSI + TUS is effective as a rapid and short-term modality for relieving PF pain. According to previous studies, the addition of TUS does not appear to make CSI much more effective.

Rheumato doi: 10.3390/rheumato3020011

Authors: Antoine Fakhry AbdelMassih Maram Hamed Hanafy Maryam ElAhmady Sylvia Kozman Nourine Diab Reem Husseiny Ashrakat Deyab Aalaa Mady Alia Yasser Amira R. AbdelHalim Aya Mohyeldin Aya Sayed Serour Ayat AbdelGadir Eslam Abdelaziz Farida ElGhamry Hana Amr Karim Milad Lamya Fouda Mawada Hesham Mina Adly Riad Mohamed Aoun Rana AbdelTawab Rana Sayed Salma ElSenbawy Sara ElAhmady Abdelkhalek Nada Gamal Yasmin Omar

Three years after its emergence, coronavirus disease 2019 (COVID-19) continues to be a leading cause of worldwide morbidity and mortality. This systematic review comprises relevant case reports that discuss non-multisystem inflammatory syndrome in children (non-MIS-C) and postacute sequalae of COVID-19 (PASC) in the paediatric population, also known as long COVID syndrome. The study aims to highlight the prevalent time interval between COVID-19 and the development of non-MIS-C post-infectious sequalae (PIS). Databases were searched for studies that met our inclusion and exclusion criteria. The final screening revealed an equal sex distribution where the commonest age intervals were school-age and adolescence, with 38% of the patients being older than six years. Interestingly, hospital admission during the course of COVID-19 was not a predictor of the subsequent PASC; forty-nine patients (44.9%) were hospitalized while sixty patients (55.1%) were not hospitalized. Moreover, the most predominant time interval between COVID-19 and the developing PASC was within 14 days from the start of COVID-19 infection (61%). These findings suggest a crucial link between COVID-19 and immune PIS in the paediatric population, especially those older than six years. Accordingly, follow-up and management are encouraged in case of unusual symptoms and signs following COVID-19 infection, regardless of the COVID-19 infection severity.

Rheumato doi: 10.3390/rheumato3020010

Authors: Natasha Proud Grace Hughes Cohen McCashney Letícia Algarves Miranda

The aim of the present study is to assess the knowledge and attitudes towards periodontal health among rheumatologists and rheumatoid arthritis (RA) patients. Two questionnaires comprising questions on demographics, knowledge, and attitudes towards periodontal health were created via Qualtrics survey software. A link to the survey was sent via email to rheumatologists registered under the Australian Rheumatology Association (ARA) practising in Western Australia, and a separate survey was distributed to patients via Arthritis and Osteoporosis WA social media pages. Seven and 76 responses were received from rheumatologists and RA patients, respectively. Statistically significant results (p < 0.05) were found between the length of RA diagnosis and signs of periodontal disease, as well as the type of RA diagnosis and knowledge levels. Employed and retired participants attended the dentist more regularly, and a higher percentage believed that maintaining good oral hygiene is important for overall health. A significant correlation was found between patients who thought improving oral hygiene would impact their RA and whether they received periodontal treatment. No significant differences were found for rheumatologists; however, younger practitioners more frequently asked about their patients’ oral health and performed oral exams. There is a deficit in knowledge about the relationship between periodontal disease and RA among both rheumatoid patients and rheumatologists. The high prevalence of periodontitis and the two-way relationship between RA and periodontal disease would benefit from improved knowledge in relation to their association and could have significant benefits in their clinical and public health implications.

Rheumato doi: 10.3390/rheumato3010009

Authors: Collins Ogbeivor Huda AlMubarak Tola Akomolafe Hamad Alkahtani Hussain AlMugizel Hala Aldosari Nouf Aldhwayan

Background: Myofascial pain syndrome (MPS) is a common, costly and often persistent musculoskeletal problem. Radial shockwave (RSW) is one of the most common treatments for MFS. However, there is very low-level evidence to support its short-term benefit, due to poor methodological qualities. Furthermore, previous studies have not considered the experiences of patients regarding this intervention. This study will investigate the effectiveness of RSW compared to a sham (placebo) for patients with MPS and establish the experiences of patients receiving the treatment. Methods: A mixed methods study of a pragmatic randomised controlled trial and semi-structured-interviews that will involve 120 potential participants with MPS is used. The intervention group will receive six sessions of RSW: 1.5 bars, 2000 pulses, frequency 15 Hz. The control group will receive an identical treatment except that they will receive a no-energy shock of 0.3 bar. Results: The outcome measures are a numeric pain scale, neck disability index (NDI), pressure pain threshold (PPT) and SF-12 questionnaires at 4 and 8 weeks’ follow-up between the two groups. Conclusion: The expectation is that this study will add to the body of knowledge required to make effective treatment choices on RSW in the management MFS.

Rheumato doi: 10.3390/rheumato3010008

Authors: AKM Kamruzzaman Maisha Farzana Md Mainuddin Sohel Emrul Kaiser Nobendu Chowdhury Md Hafizur Rahman Syed Atiqul Haq Johannes J. Rasker

Pachydermoperiostosis (PDP), also called primary hypertrophic osteoarthropathy (HOA), is a rare genetic disease with typical thickening of the skin (pachydermia) and rheumatic manifestations, with clubbing of the fingers and toes and periostosis of the long bones visible on X-rays, as well as arthritis in large joints sometimes. Case: We describe a 23-year-old man with a complete form of PDP who presented with polyarthritis of the ankles and knees, with clubbing of the fingers and toes. He was treated with a non-steroidal anti-inflammatory drug (NSAID), etoricoxib, and with bisphosphonates (initially pamidronic acid i.v. and later oral risedronate 35 mg weekly). His joint pains and swelling disappeared, so that he could resume his daily activities. After eight years, the periostosis on the X-rays had disappeared. Discussion: The case is discussed, the literature regarding PDP is summarized and the differential diagnosis and treatment options are reviewed. Conclusions: PDP may present as polyarthritis. Clinicians should be aware of this diagnosis, as treatment is available and may improve the outcome of the patient. It is important to rule out secondary HOA due to pulmonary or cardiac disease, gastrointestinal malignancies and liver cirrhosis, especially when the dermatological findings are not typical. Further, acromegaly, thyroid acropachy and rheumatologic diseases should be excluded.

Rheumato doi: 10.3390/rheumato3010007

Authors: Sern Chin Lim Elaine Wan Ling Chan Shikriti Suprakash Mandal Swee Ping Tang

Proliferative lupus nephritis, which is diagnosed by renal biopsy, has significant impact on the treatment choices and long-term prognosis of juvenile SLE (jSLE). Renal biopsies are however not always possible or available, thus leading to an ongoing search for alternative biomarkers. This study aimed to develop a clinical predictive machine learning model using routine standard parameters as an alternative tool to evaluate the probability of proliferative lupus nephritis (ISN/RPS Class III or IV). Data were collected retrospectively from jSLE patients seen at Selayang Hospital from 2004 to 2021. A total of 22 variables including demographic, clinical and laboratory features were analyzed. A recursive feature elimination technique was used to identify factors to predict pediatric proliferative lupus nephritis. Various models were then used to build predictive machine learning models and assessed for sensitivity, specificity and accuracy. There were 194 jSLE patients (165 females), of which 111 had lupus nephritis (54 proliferative pattern). A combination of 11 variables consisting of gender, ethnicity, fever, nephrotic state, hypertension, urine red blood cells (RBC), C3, C4, duration of illness, serum albumin, and proteinuria demonstrated the highest accuracy of 79.4% in predicting proliferative lupus nephritis. A decision-tree model performed the best with an AROC of 69.9%, accuracy of 73.85%, sensitivity of 78.72% and specificity of 61.11%. A potential clinically useful predictive model using a combination of 11 non-invasive variables to collectively predict pediatric proliferative lupus nephritis in daily practice was developed.

Rheumato doi: 10.3390/rheumato3010006

Authors: Marcos Ortiz-Uriarte Jeanlouis Betancourt-Gaztambide Alexandra Perez Youssef M. Roman

Gout is one of the most common inflammatory conditions with a growing global prevalence. Individuals with gout are at higher risk of developing chronic conditions, such as diabetes, chronic kidney disease (CKD), and cardiovascular diseases. In this study, the association between urate-lowering therapy (ULT) use and the prevalence of these conditions was evaluated. This observational cross-sectional pharmacoepidemiologic study used the 2013–2018 biannual cycles of the National Health and Nutrition Examination Survey. The inclusion criteria were adults that were 30 years of age or older that had a diagnosis of gout. The association between patients’ ULT treatment status and dyslipidemia, coronary heart disease, heart failure, hypertension, and chronic kidney disease was evaluated as well as its association with select clinical laboratory biomarkers. The prevalence of ULT use was 28.9% (95% CI 24.3–33.9%). Those receiving ULT had a higher prevalence of CKD diagnoses, of a college graduate or higher and of health insurance coverage, and they were older obese males. There was no significant association between ULT use and the prevalence of heart failure, coronary heart disease, hypertension, or dyslipidemia (p > 0.05). Those receiving ULT had lower high-sensitivity c-reactive protein levels compared to those who were not on treatment (4.74 versus 7.21 mg/L, p = 0.044). LDL and total cholesterol were significantly lower among those receiving ULT treatment (p < 0.05). ULT use continues to be low among US individuals diagnosed with gout. Socioeconomic factors may influence patients’ ULT treatment status. Also, gout risk factors, including obesity, male sex, and CKD, are associated with receiving ULT. While our findings may have reflected the guideline recommendations for ULT use in CKD patients, worsening kidney functions while receiving ULT is unlikely. Gout patients receiving ULT may garner added health benefits beyond lower urate levels. Further research is necessary to determine the long-term impact of ULTs on lipid fractions, kidney functions, and other cardiovascular biomarkers.

Rheumato doi: 10.3390/rheumato3010005

Authors: Pedro Aleixo Orlando Fernandes José Vaz Patto João Abrantes

This study compared rheumatoid arthritis (RA) post-menopausal women with pathological involvement of the lower limb joints and age-matched post-menopausal women without RA regarding the dynamic joint stiffness (DJS) of knee during the stance phase of gait. Eighteen RA women and eighteen age-matched women were selected. Gait assessed through a three-dimensional motion analysis system synchronized with a force plate. Subjects walked barefoot at self-selected speed, and 14 valid trials were collected (comprising 7 left and 7 right foot-steps on force plate). The “moment of force—angle” plot of knee in sagittal plane was determined. The stance phase was split into three sub-phases: first knee flexion sub-phase (1st KFS); knee extension sub-phase (KES); second knee flexion sub-phase (2nd KFS). A linear model represented each sub-phase and DJS calculated by the slope. Model fitting was assessed through the coefficient of determination (R2). R2 values for both groups were higher than 0.8 during 1st KFS and KES but not during 2nd KFS. RA women yielded a higher DJS value during 2nd KFS (p < 0.01). Concerning the other sub-phases, no differences were observed between groups. The findings suggested the splitting methodology used could be modelled by a linear “moment of force—angle” relationship, namely, during 1st KFS and KES. During 2nd KFS, RA women yielded a stiffer behavior.

Rheumato doi: 10.3390/rheumato3010004

Authors: Komal Chhikara Shubham Gupta Sakshi Saharawat Shruti Sarkar Arnab Chanda

Rheumatoid arthritis has become one of the most common inflammatory diseases and plays a major role in the disability of the population affected by it. The prevalence of finger deformities in the upper extremity caused by rheumatoid arthritis is increasing day by day, especially in low and middle-income countries such as India. For the management of these finger deformities, the splinting options are either customized or prefabricated. The performance and success of finger splinting depend on several factors, including precision, aesthetics, patient acceptance, comfort, the convenience of usage, effects, price, and side effects. However, to date, customized splints are high-cost and usually fabricated by conventional production techniques, which dominantly work on approximation. This study focused on the development of a novel finger splint through computational optimization and 3D printing for the management of boutonniere and swan neck deformity caused by rheumatoid arthritis. Twenty subjects with finger deformities were recruited, and the performance of the 3D-printed splint was characterized. The results were assessed using the nine-hole peg test and QUEST 2.0, which showed positive effects of the splint, including achievement of corrected joint positions, finger dexterity, and comfort. Such a low-cost and effective splint, with further acceptability testing, is anticipated to be a better line of conservative management for patients affected by rheumatoid arthritis.

Rheumato doi: 10.3390/rheumato3010003

Authors: Ian Burton

Tendinopathy is a chronic tendon disease which can cause significant pain and functional limitations for individuals, and which collectively places a tremendous burden on society. Resistance training has long been considered the treatment of choice in the rehabilitation of chronic tendinopathies, with both eccentric and heavy slow resistance training demonstrating positive clinical effects. The application of progressive tendon loads during rehabilitation is essential to not compromise tendon healing, with the precise dosage parameters of resistance training and external loading a critical consideration. Blood-flow restriction training (BFRT) has become an increasingly popular method of resistance training in recent years and has been shown to be an effective method for enhancing muscle strength and hypertrophy in healthy populations and in musculoskeletal rehabilitation. Traditional resistance training for tendinopathy requires the application of heavy training loads, whereas BFRT utilises significantly lower loads and training intensities, which may be more appropriate for certain clinical populations. Despite evidence confirming the positive muscular adaptations derived from BFRT and the clinical benefits found for other musculoskeletal conditions, BFRT has received a dearth of attention in tendon rehabilitation. Therefore, the purpose of this narrative review was threefold: firstly, to give an overview and analysis of the mechanisms and outcomes of BFRT in both healthy populations and in musculoskeletal rehabilitation. Secondly, to give an overview of the evidence to date on the effects of BFRT on healthy tendon properties and clinical outcomes when applied to tendon pathology. Finally, a discussion on the clinical utility of BFRT and its potential applications within tendinopathy rehabilitation, including as a compliment to traditional heavy-load training, is presented.

Rheumato doi: 10.3390/rheumato3010002

Authors: Mark Sharobim Angelica S. J. Scribner William N. Rose

About 2% of mothers with Sjögren’s syndrome and about 1% of mothers with systemic lupus erythematosus deliver a baby with a congenital heart block (CHB). This is thought to be as a result of the maternal autoantibodies that cross the placenta and cause congenital lupus in the fetus/neonate. Among patients with a 2nd or 3rd degree atrioventricular block, the mortality rate in the neonatal period is about 10%, and most neonates who survive require a pacemaker into adulthood. Despite the compelling mortality and morbidity, the data on the optimal preventive treatments are meager and not well-established. In addition to pharmaceutical therapy, one potentially effective therapy is plasmapheresis. Plasmapheresis is safe in pregnancy, well tolerated, and is effective in removing the offending substances in the serum which may cause disease. We review this literature, in order to educate the reader and to motivate interest in studying this condition in the future.

Rheumato doi: 10.3390/rheumato3010001

Authors: Tamara Lee Ting Soh Nicholas Li Khai Loh Sean Wei Loong Ho Arun-Kumar Kaliya-Perumal Chung Yuan Kau

Unicompartmental and Total Knee Arthroplasty (UKA and TKA) are both established surgical options for the treatment of medial compartment osteoarthritis of the knee. However, the superiority of one over the other remains controversial. Our retrospective study aims to compare short-term functional outcomes in similar patients who underwent either TKA or UKA. Pre- and post-operative range of motion (ROM), the Oxford Knee Score (OKS), Knee Society Knee Score (KSKS), and Knee Society Function Score (KSFS) were used as outcome measures. Our sample included 57 patients, among which 27 underwent TKA and 30 underwent UKA, including one patient who underwent bilateral UKA. At 1 year, there were no differences in the OKS, KSKS, or KSFS scores between the two groups. There was a significantly better range of motion in patients who underwent UKA compared to TKA (122.9 ± 11.7 degrees vs 109.9 ± 13.9 degrees, p < 0.001). Functional outcomes following UKA and TKA were found to be similar. Hence, in view of its lower morbidity and shorter length of hospital stay, UKA may be considered over a TKA for the treatment of medial compartment osteoarthritis whenever deemed appropriate.

Rheumato doi: 10.3390/rheumato2040016

Authors: Ana Alonso-Pérez María Guillán-Fresco Miriam López-Fagúndez Andrés Pazos-Pérez Antía Crespo-Golmar María Piñeiro-Ramil Verónica López Alberto Jorge-Mora Rodolfo Gómez

Current lifestyle and environmental factors contribute to obesity development, leading to low-grade chronic inflammation (LGCI). Apart from obesity, LGCI is also related to rheumatic diseases such as osteoporosis (OP) and osteoarthritis (OA). In these, an excessive accumulation of adipose tissue has been linked to an excessive production of proinflammatory factors, such as adipokines. This work’s aim is to stablish the effect of obesity-associated LGCI in major rheumatic diseases and to determine optimal strategies to reduce it. Obesity is a risk factor for developing OA, where a systemic LGCI state has been found. Concretely, obesity-associated LGCI has been described as an OA instauration and progression promoter. To avoid this, several therapeutical approaches (diet control, physical exercise, or nutraceuticals) have been tested. OP is another major rheumatic disease where a basal LGCI has been described, being worsened by obesity. As in OA, diet management and supplementation with vitamin D or probiotics have been proposed as approaches to treat obesity-associated LGCI in this pathology. Currently, the increase in the prevalence of rheumatic diseases is unstoppable. Nonetheless, obesity is a risk factor that can be controlled. Thus, the study of new interventions to control the impact of obesity-associated LGCI is a challenge for the management of patients with rheumatic diseases.

Rheumato doi: 10.3390/rheumato2040015

Authors: Bruce Rothschild

The inaugural issue of Rheumato exhibits the gamut of phenomenology that is inherent to why we became rheumatologists: our reliance on fundamentals, the quest to decipher apparently disparate findings, problem solving, hypothesis formation as to mechanisms and relationships, assessing the applicability and adaptability of new technologies and exploring the validity of old concepts/perspectives, and constantly reviewing our perspectives and performance [...]

Rheumato doi: 10.3390/rheumato2040014

Authors: David Cosio Madison Simons

Background: Efforts to increase acceptance and reduce avoidance behaviors in patients who suffer from chronic pain are likely to have additional beneficial effects on pain management. The primary aim of the current study was to evaluate whether a sequential approach to treatment, where acceptance-based coping strategies are taught prior to problem-focused coping strategies using manualized group therapies, improves pain-related outcomes. Methods: The current investigation is a single-group, longitudinal ex post facto study. A sample of 168 Veterans participated in the current study at a midwestern VA medical center. All participants were administered a standard pre- and post-intervention assessment battery. The primary outcome analysis was a 4 × 2 repeated-measures multivariate analysis of variance. Results: The current study did not find a significant interaction effect for intervention x time but did find a significant main effect for time. All treatment conditions were associated with decreases in pain severity, pain interference, illness-focused coping strategies, catastrophizing behaviors, and global distress. Participation in both of the combined groups did not produce significantly different pain-related outcomes compared to participation in one group. Conclusion: These findings reinforce common factors theory in psychotherapy and provide insight into treatment dosage for patients who suffer from chronic pain. The current findings underline the importance of researching pain management, as it is a fundamental aspect of clinical practice, training, and research in rheumatology.

Rheumato doi: 10.3390/rheumato2040013

Authors: Samaher Almousa Hala Wannous Kamar Khedr Heba Qasem

Systemic Lupus Erythematosus (SLE) is a chronic multisystem autoimmune disease. Serositis occurs in 16% of SLE patients, and while cardiac tamponade and acute peritonitis with ascites can occur during the course of the disease, they are rare as the first presentation. A 25-year-old woman presented to the emergency department in Tishreen Hospital with complaints of dyspnea, fever, chills, and chest and abdominal pain. Two months prior, she suffered from musculoskeletal pain, fatigue, anorexia, weight loss of about 15 kg, severe hair loss, and recurrent oral aphthous. On clinical examination, the patient was pale and tired with dyspnea and pitting edema (grade 3–4). Pericardiocentesis was emergently performed because there were signs of cardiac tamponade. Three days later, the patient developed an acute surgical abdomen due to acute peritonitis and ascites. Later, the patient was diagnosed with SLE after excluding malignant and infectious diseases. Consequently, methylprednisolone pulses, azathioprine, and hydroxychloroquine 200 mg/day were introduced immediately. The clinical status of the patient dramatically improved, and three months later, the patient was symptom-free with normal laboratory tests. In conclusion, although cardiac tamponade and acute surgical abdomen because of acute peritonitis and ascites as the initial presentation of SLE are very rare, they can occur coincidently.

Rheumato doi: 10.3390/rheumato2040012

Authors: Bruce Rothschild

Scientific methodology (logos) is predicated upon generating hypotheses and testing them, following where the collected data and evidence lead [...]

Rheumato doi: 10.3390/rheumato2040011

Authors: Bruce Rothschild

The current time/experience allotted for rheumatology in primary care education seems like paying lip service to a medical education clinical approach consisting of: 1 [...]

Rheumato doi: 10.3390/rheumato2030010

Authors: Jun Shimizu Masanori A. Murayama Yoshishige Miyabe Noboru Suzuki

The impact of the microbiota residing in the body on local and systemic immune responses has been increasingly recognized. The major gut microbe metabolites’ short-chain fatty acids (SCFAs) are suggested to regulate the balance between regulatory (Treg) cells and helper T 17 (Th17) cells in physiological and pathological conditions by enhancing regulatory T (Treg) cell function through epigenetic modifications. Patients with Behcet’s disease (BD) exhibited enhanced Th17 cell-mediated immune responses and decreased intestinal relative abundances of SCFA-producing bacteria. Causal correlations between aberrant immune responses and gut microbial composition in patients with BD have been reported in Italy, the Netherlands, Turkey, China, and Japan. We reported that the gut and oral microbiota profiles of patients with BD shared some common features. Immune responses against both commensal and pathogenic microbes may play a crucial role in BD development. This review summarizes the current literature, which was retrieved from public databases, such as PubMed and MEDLINE using search terms, including Behcet’s disease, helper T cells, and microbiota, during 1970–2022, on the potential functional correlation between immune cells and microbiota in patients with BD.

Rheumato doi: 10.3390/rheumato2030009

Authors: Takafumi Tomizuka Hirotoshi Kikuchi Kurumi Asako Hajime Kono

Rheumatoid meningitis, a very rare complication, is not well-recognised, and there are few reports describing its treatment. We report the case of a 74-year-old Japanese woman who was diagnosed with rheumatoid meningitis by characteristic brain magnetic resonance imaging (MRI) and was successfully treated with glucocorticoids. We observed fluid-attenuated inversion recovery and diffusion-weighted imaging hyperintensity, which had a meningeal gadolinium-enhancing characteristic of rheumatoid meningitis. We suggest that it is possible to diagnose this disease based on characteristic MRI findings and treat patients early using glucocorticoids.

Rheumato doi: 10.3390/rheumato2030008

Authors: Alexander V. Tarakanov Elena S. Ladanova Alexander A. Lebedenko Tatyana D. Tarakanova Sergey G. Vesnin Tatyana Kharybina Igor I. Goryanin

Juvenile idiopathic arthritis (JIA) is a disease with unknown causes in all forms of arthritis in children under 16 years of age. It is diagnosed when other joint pathologies are excluded. Difficulties in early and differential diagnoses lead to rapid disability and an unfavorable life prognosis. Therefore, a timely diagnosis is necessary to prevent irreversible damage to joints and preserve their function. Due to the widespread use of new technologies, modern multimodal imaging has gained recognition, including radiography, ultrasound, and MRI. The combination of methods plays a key role in confirming the diagnosis, monitoring the disease activity, the prognosis during the disease course, and the outcome in children with JIA. Each method has its advantages and disadvantages. The introduction of passive microwave radiometry (MWR), in combination with other imaging methods, makes it possible to expand the possibilities of screening the disease in the preclinical and early clinical phases.

Rheumato doi: 10.3390/rheumato2030007

Authors: Bruce M. Rothschild

Diagnoses for which there are no pathognomonic laboratory tests are highly dependent on the opinions we call clinical judgement [...]

Rheumato doi: 10.3390/rheumato2020006

Authors: Kenneth P. H. Pritzker Andrea R. Pritzker

From ancient times to the present day, gout has been associated in the popular and scientific literature with wealthy men who overindulge in fancy foods, fine wine, and debauchery. Curiously, amongst diseases, gout was thought to be good, a malady to be accepted because of otherwise beneficial effects on health, and longevity. This narrative review critically examines the history of these associations and explores in detail the pathogenic factors contributing to development of gout prior to the 20th century. While lead toxicity has been previously implicated with wine, the specific association of gout and fine wine can be attributed to lead complexes in products such as sapa, a grape extract used to sweeten wine, in addition to lead nanoparticles leached from crystal glassware and lead glazed dinner plates. The health benefits of gout can be attributed to lead complexes in fine wine and lead nanoparticles from glazed dinnerware. These compounds have excellent antibacterial properties, thereby inhibiting the presence of pathogenic bacteria in foodstuffs. Probing the association of gout and fine wine provides a very well documented example of how the pathogenesis of disease becomes better understood with the passage of time and continuing, persistent scientific enquiry.

Rheumato doi: 10.3390/rheumato2020005

Authors: Gillian Hendriks Suresh Chandran

Kawasaki disease (KD) is an acute febrile illness, principally affecting children under 5 years, due to a systemic vasculitis of obscure etiology. In 2017, the American Heart Association published the diagnostic criteria for KD in their scientific statement. Following the emergence of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there has been an upsurge in the reports of KD as well as a novel multisystem inflammatory syndrome in children (MIS-C). Clinical manifestations of MIS-C are similar to KD and toxic-shock syndrome, making the clinical diagnosis challenging. Studies have shown promising results to differentiate KD from MIS-C using epidemiological, clinical, hematological, and immunological characteristics. Serological evidence may be negative in these patients at presentation, as MIS-C is a late manifestation of SARS-CoV-2 exposure. However, diagnosis and management challenges currently exist due to a gap in knowledge of these conditions. Further research is warranted to identify diagnostic tools to differentiate KD and MIS-C and optimize the therapeutic strategy, reducing morbidity and mortality related to these phenotypically similar diseases. This review aims to highlight the best available evidence for managing children with KD and MIS-C in the background of the ongoing COVID-19 pandemic.

Rheumato doi: 10.3390/rheumato2010004

Authors: Yuichi Nomura Yuta Mikami Kiminori Masuda Yoshikazu Kato Naho Nakazaki Hiromi Ikeda Masako Hirabayashi Ryo Kusubae Koji Sameshima

Background: We examined the characteristics of Kawasaki disease (KD) patients who presented with limited and faint principal clinical features. Methods: We retrospectively reviewed the clinical records of 62 KD patients who presented with limited and faint clinical features at admission. A clinical feature that was recognizable by even junior doctors was defined as a definite feature (d-Feature), and a feature that was faint and recognizable by only experienced doctors was defined as a faint feature (f-Feature). Results: At admission, 82% of patients presented with fever and ≤1 d-Feature. Two days later, the d-Features increased in number and diagnoses of KD were established in 32 patients with fever and ≥4 d-Features. In 30 patients with ≤3 d-Features, experienced doctors recognized f-Features and diagnosed KD in 22 patients because of fever and ≥4 features. Among eight patients with ≤3 features, experienced doctors diagnosed six patients as incomplete KD considering their faint abnormal echocardiographic findings. For the remaining two patients, experienced doctors decided to commence KD treatments considering the patients’ clinical course. Conclusions: Sufficient clinical experience is essential during the diagnosis of KD in patients presenting with limited and f-Features. Educational programs for junior doctors on how to recognize f-Features and evaluate faint abnormal coronary artery findings are necessary.

Rheumato doi: 10.3390/rheumato2010003

Authors: Matilde Bandeira Ângela Gil Ana Carolina Santos Vasco C. Romão Mário Rui Mascarenhas Paulo Filipe João Eurico Fonseca Manuel Bicho

Psoriasis is a multifactorial disease, with many genetic risk factors, one of which seems to be the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism. ACE activity has been shown to be higher in psoriatic patients and it suggests an oxidative stress state, as seen in many cardiovascular disorders. We aimed to explore the association between ACE activity and polymorphisms and cardiovascular risk amongst psoriatic patients. We included 64 psoriatic patients and 1091 controls and compared ACE I/D polymorphism genotype and serum activity for both groups. ACE genotypes were similar in psoriatic patients and controls. Notably, serum ACE activity was higher in psoriatic patients (19.09 ± 2.86 U/mL) compared to controls (11.85 ± 0.40 U/mL), p = 0.015. Non-HDL cholesterol was significantly lower in II polymorphism (p = 0.037). Psoriatic activity (PASI) was associated with a higher cardiovascular risk estimated by lower HDL concentrations (r = −0.496, p = 0.007), and higher triglyceride levels (r = 0.421, p = 0.020) and TC/HDL and LDL/HDL ratios (r = 0.612, p < 0.001 and r = 0.437, p = 0.023, respectively). Patients with psoriasis have higher ACE activity levels, independent of ACE genotype. Moreover, disease activity correlated with cardiovascular risk. This could support the eventual role of ACE as a possible biomarker for disease severity and cardiovascular risk in psoriasis patients.

Rheumato doi: 10.3390/rheumato2010002

Authors: Doaa Mosad Mosa Ashraf M. Abdelrahman Amany S. El-Bahnasawy

Objective: The aim of this study was to evaluate musculoskeletal ultrasound (MSUS) features across categories of juvenile idiopathic arthritis (JIA). Methods: In this cross-sectional study, all patients were subjected to full history taking, clinical examination including disease assessment parameters and laboratory investigations. In addition, all children were examined by both grayscale (GS) and power Doppler (PD) MSUS images. Results: By MSUS, the number of joints with synovial effusion was 697 of a total 2400 examined joints (29%) and joints with synovial thickening counted 673 (28%). The number of joints with positive PD signals was 446 (18.6%). There was a significant difference among JIA subtypes as regards different MSUS features. Moreover, there was a discrepancy regarding synovial effusion (p = 0.018), hypertrophy scores (p = 0.013), and the total US severity score (p = 0.026). This divergence was attributed to the significant difference between systemic juvenile idiopathic arthritis (SJIA) and other categories. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of MSUS in JIA and its subtypes were calculated. Conclusion: MSUS is a highly sensitive method for detecting synovitis, tenosynovitis, and erosive bone disease, and it helps to make proper therapeutic decisions. There was a significant difference among JIA subtypes regarding MSUS features.

Rheumato doi: 10.3390/rheumato2010001

Authors: Rheumato Editorial Office Rheumato Editorial Office

Rigorous peer-reviews are the basis of high-quality academic publishing [...]

Rheumato doi: 10.3390/rheumato1010005

Authors: Antonio Giovanni Versace Caterina Oriana Aragona Daniela La Rosa Marianna Chiappalone Maria Concetta Tringali Alberta De Gaetano Charles Frederick Moore Donatella Sangari William Neal Roberts Gianluca Bagnato

Introduction/Objective: The efficacy of biologic therapy in the treatment of rheumatoid arthritis (RA) has been well-established but, in practice, a quarter of patients will either not respond to the first biologic agent or will suffer an adverse event requiring a switch to a different drug. While clinical guidelines exist to help guide therapy and previous studies have examined sequential use of anti-TNF agents, there is little data to inform a multiple switch strategy. Our aim was to measure the efficacy of multiple switches of biologic in severe refractory RA. Methods: We enrolled 111 patients whose therapy with one anti-TNF agent had failed in this open-label observational study. These patients were all treated with a second biologic agent and 27 ultimately required treatment with a third. The response to the therapy and disease activity were assessed at 6 and 12 months after each switch. Results: The remission rates at 6 months were lower than previously reported and the initiation of a second biologic agent resulted in significant improvement at 12 months, including DAS remission in 36% of patients. The response in those receiving a third biologic was less pronounced, as might be expected in this relatively treatment-refractory population. In this group, only patients treated with tocilizumab had maintained remission at one year. Conclusion: Patients who do not respond to an anti-TNF agent often benefit from being switched to a second, or even third, biologic. Importantly, it may take longer than expected to fully assess the effectiveness of a second or third agent in patients with refractory disease.

Rheumato doi: 10.3390/rheumato1010004

Authors: Elena Vanni Jacopo Ciaffi Luana Mancarella Francesco Ursini

The rare occurrence of polymyalgia rheumatica (PMR) in married couples has been reported in the literature. Susceptibility to PMR is contributed by genetic and environmental factors and cases of PMR developing after influenza vaccine have also been described, in a debated phenomenon known as ‘ASIA’ syndrome. We report the case of two cohabitating married patients developing PMR few weeks after the first dose of ChAdOx1-S SARS-CoV-2 vaccine. Both patients presented with typical symptoms suggestive of PMR. Laboratory findings and ultrasound examination confirmed the diagnosis. Glucocorticoid therapy led to rapid improvment of symptoms. Anti-receptor-binding domain IgG titre was tested and, eight weeks after vaccination, both patients showed no antibody response. It has been suggested that vaccines might trigger autoimmune or inflammatory states in predisposed individuals and various hypotheses have been made regarding the pathogenesis of PMR. Although the causative effect of vaccines cannot be determined, the close temporal correlation observed in our case supports the potential role of environmental factors in triggering the onset of PMR. However, the literature indicates that post-COVID19 vaccination immune-mediated or inflammatory adverse events are extremely rare and vaccination should be encouraged since the benefit largely outweighs possible risks.

Rheumato doi: 10.3390/rheumato1010003

Authors: Francesca Oliviero Paola Galozzi Elisabetta Zanatta Mariele Gatto Paolo Spinella Andrea Doria

The aim of this review is to identify and discuss randomized clinical trials conducted in patients with connective tissue diseases, including systemic lupus erythematosus, idiopathic inflammatory myopathies, vasculitis, Sjögren’s syndrome, and systemic sclerosis. Although limited, the results obtained with bioactive compounds, namely n-3 polyunsaturated and short-chain fatty acids, demonstrate that dietary intervention and nutritional counseling might have an important role as adjuvant therapy in patients with connective tissue diseases, particularly in the light of the comorbidities which characterize these conditions.

Rheumato doi: 10.3390/rheumato1010002

Authors: Bruce M. Rothschild

In the spirit of initiating a new journal for Rheumato, it is pertinent to review the attention to the basics that first established the field as an evidence-based approach to recognition and treatment of arthritis and multisystem diseases and the reputation of its disciples as resources for solving diagnostic dilemmas [...]

Rheumato doi: 10.3390/rheumato1010001

Authors: Clàudia Aunós

As one of the top four scholarly journal publishers in the world [...]