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INTRODUCTION: An altered immune tolerance disturbed by immune checkpoint inhibitors (ICIs) may contribute to new-onset polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). This systematic literature review (SLR) examines the characteristics of PMR and GCA-like syndromes following anticancer treatment with ICIs, summarizing their demographic, clinical and treatment-related features to provide insights whether they differ from the idiopathic forms. METHODS: The SLR was conducted in Medline and EMBASE databases from inception to July 2024, and in the EULAR/ACR abstract database (2021-2023). ICI-induced PMR and GCA syndromes were compared to the primary forms of the diseases using data from studies that included both groups as comparators. For manuscripts lacking direct comparisons, we summarized the main findings and discussed the differences using systematic reviews or large observational studies on the primary forms. RESULTS: From 1237 screened abstracts, 46 met the inclusion criteria, involving 358 patients (314 with ICI-PMR and 44 with ICI-GCA). ICI-PMR had an estimated pooled prevalence of 0.1% [95% CI: 0.07%, 0.14%] among ICI recipients and 15.9% [95% CI: 12.6%, 19.9%] among patients experiencing rheumatic immune-related adverse events. Patients with ICI-PMR had a male-to-female ratio of 1.7:1 and a mean age of 71 ± 4 years. Most cases were associated with PD1/PDL1 blockers (87%). Clinical features included inflammatory pain in the girdles (100%), though pelvic girdle involvement was under-reported in some cases (3/28 studies). Peripheral arthritis was present in 35% of patients. Laboratory tests showed normal or slightly elevated inflammatory markers in 26% of cases. Glucocorticoids (GCs) led to symptom improvement in 84% of cases although 20% required immunosuppressive treatment and 14% experienced relapses. ICI-GCA had a prevalence of 0.06% among ICI recipients, with equal gender distribution and a mean age of 71 ± 5 years. Most patients received anti-PD1/PDL1 blockers (57%). Clinical manifestations included cephalic symptoms (75%), permanent visual loss (23%) and symptoms related to large-vessel involvement (54%). High-dose GCs were effective, with 96% achieving remission, though 17% experienced relapses. CONCLUSIONS: ICI-induced PMR and GCA may have distinct clinical profiles compared to idiopathic forms, with potentially milder symptoms and better treatment responses. Further studies are needed to confirm these findings and better understand the long-term outcomes and pathophysiology of these conditions.
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Background and Objectives: Vitamin D is a secosteroid hormone essential for calcium homeostasis and skeletal health, but established evidence highlights its significant roles also in muscle health and in the modulation of immune response. This review aims to explore the impact of impaired vitamin D status on outcomes of muscle function and involvement in inflammatory and autoimmune rheumatic diseases damaging the skeletal muscle efficiency both with direct immune-mediated mechanisms and indirect processes such as sarcopenia. Methods: A comprehensive literature search was conducted on PubMed and Medline using Medical Subject Headings (MeSH) terms: "vitamin D, muscle, rheumatic diseases." Additionally, conference abstracts from The European Alliance of Associations for Rheumatology (EULAR) and the American College of Rheumatology (ACR) (2020-2023) were reviewed, and reference lists of included papers were scanned. The review emphasizes the evidence published in the last five years, while also incorporating significant studies from earlier years, structured by the extent of evidence linking vitamin D to muscle health in the most commonly inflammatory and autoimmune rheumatic diseases encountered in clinical practice. Results: Observational studies indicate a high prevalence of vitamin D serum deficiency (mean serum concentrations < 10 ng/mL) or insufficiency (<30 ng/mL) in patients with idiopathic inflammatory myopathies (IIMs) and polymyalgia rheumatica, as well as other autoimmune connective tissue diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). Of note, vitamin D insufficiency may be associated with reduced muscle strength (2 studies on RA, 2 in SLE and 1 in SSc), increased pain (1 study on SLE), fatigue (2 studies on SLE), and higher disease activity (3 studies on IIMs and 1 on SLE) although there is much heterogeneity in the quality of evidence and different associations for the different investigated diseases. Therefore, linked to the multilevel biological intervention exerted by vitamin D, several translational and clinical studies suggest that active metabolites of this secosteroid hormone, play a role both in reducing inflammation, but also in enhancing muscle regeneration, intra-cellular metabolism and mitochondrial function, although interventional studies are limited. Conclusions: Altered serum vitamin D status is commonly observed in inflammatory and autoimmune rheumatic diseases and seems to be associated with adverse muscle health outcomes. While maintaining adequate serum vitamin D concentrations may confer muscle-protective effects, further research is needed to confirm these findings and establish optimal supplementation strategies to obtain a safe and efficient serum threshold.
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Enfermedades Autoinmunes , Músculo Esquelético , Enfermedades Reumáticas , Deficiencia de Vitamina D , Vitamina D , Humanos , Vitamina D/sangre , Deficiencia de Vitamina D/complicaciones , Músculo Esquelético/metabolismo , Miositis , Sarcopenia , InflamaciónRESUMEN
INTRODUCTION: Rheumatoid arthritis (RA), the most prevalent autoimmune disease in reproductive years, exhibits a higher incidence in females, suggesting involvement of estrogens, genetics and environmental factors in disease onset. Literature shows smaller families in RA patients, driving increased interest in Assisted Reproductive Techniques. AREAS COVERED: This review elucidates how immunotolerance mechanisms contribute to favorable pregnancy outcomes in RA, emphasizing the need for a careful pregnancy planning to mitigate fetal complications and postnatal flares, which surpass those in the general population. A thorough medication evaluation, orchestrated by a multidisciplinary team, is imperative during pregnancy, weighing potential teratogenic effects against safer alternatives to balance medication safety with disease control. A systematic literature search on PubMed and MEDLINE, using specific terms, covered relevant academic journals up to the latest date. EXPERT OPINION: This narrative review comprehensively addresses pregnancy-related considerations in RA patients, prioritizing meticulous disease management with pregnancy and breastfeeding-compatible drugs in line with the latest recommendations and registry data. The focus remains on evaluating glucocorticoids, conventional, and biological disease-modifying drugs for compatibility during pregnancy and breastfeeding. Additionally, the evolving landscape of targeted synthetic drugs during pregnancy is explored, providing insights into the latest developments in rheumatological care.
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Artritis Reumatoide , Complicaciones del Embarazo , Humanos , Embarazo , Artritis Reumatoide/inmunología , Artritis Reumatoide/tratamiento farmacológico , Femenino , Complicaciones del Embarazo/inmunología , Antirreumáticos/uso terapéutico , Lactancia Materna , Resultado del Embarazo , Glucocorticoides/uso terapéuticoRESUMEN
BACKGROUND: Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by vasculopathy and progressive fibrosis of skin and several internal organs, including lungs. Macrophages are the main cells involved in the immune-inflammatory damage of skin and lungs, and alternatively activated (M2) macrophages seem to have a profibrotic role through the release of profibrotic cytokines (IL10) and growth factors (TGFß1). Nintedanib is a tyrosine kinase inhibitor targeting several fibrotic mediators and it is approved for the treatment of SSc-related interstitial lung disease (ILD). The study aimed to evaluate the effect of nintedanib in downregulating the profibrotic M2 phenotype in cultured monocyte-derived macrophages (MDMs) obtained from SSc-ILD patients. METHODS: Fourteen SSc patients, fulfilling the 2013 ACR/EULAR criteria for SSc, 10 SSc patients affected by ILD (SSc-ILD pts), 4 SSc patients non affected by ILD (SSc pts no-ILD), and 5 voluntary healthy subjects (HSs), were recruited at the Division of Clinical Rheumatology-University of Genova, after obtaining Ethical Committee approval and patients' informed consent. Monocytes were isolated from peripheral blood, differentiated into MDMs, and then maintained in growth medium without any treatment (untreated cells), or treated with nintedanib (0.1 and 1µM) for 3, 16, and 24 h. Gene expression of macrophage scavenger receptors (CD204, CD163), mannose receptor-1 (CD206), Mer tyrosine kinase (MerTK), identifying M2 macrophages, together with TGFß1 and IL10, were evaluated by quantitative real-time polymerase chain reaction. Protein synthesis was investigated by Western blotting and the level of active TGFß1 was evaluated by ELISA. Statistical analysis was carried out using non-parametric Wilcoxon test. RESULTS: Cultured untreated SSc-ILD MDMs showed a significant increased protein synthesis of CD206 (p < 0.05), CD204, and MerTK (p < 0.01), together with a significant upregulation of the gene expression of MerTK and TGFß1 (p < 0.05; p < 0.01) compared to HS-MDMs. Moreover, the protein synthesis of CD206 and MerTK and the gene expression of TGFß1 were significantly higher in cultured untreated MDMs from SSc-ILD pts compared to MDMs without ILD (p < 0.05; p < 0.01). In cultured SSc-ILD MDMs, nintedanib 0.1 and 1µM significantly downregulated the gene expression and protein synthesis of CD204, CD206, CD163 (p < 0.05), and MerTK (p < 0.01) compared to untreated cells after 24 h of treatment. Limited to MerTK and IL10, both nintedanib concentrations significantly downregulated their gene expression already after 16 h of treatment (p < 0.05). In cultured SSc-ILD MDMs, nintedanib 0.1 and 1µM significantly reduced the release of active TGFß1 after 24 h of treatment (p < 0.05 vs. untreated cells). CONCLUSIONS: In cultured MDMs from SSc-ILD pts, nintedanib seems to downregulate the profibrotic M2 phenotype through the significant reduction of gene expression and protein synthesis of M2 cell surface markers, together with the significant reduction of TGFß1 release, and notably MerTK, a tyrosine kinase receptor involved in lung fibrosis.
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Indoles , Enfermedades Pulmonares Intersticiales , Esclerodermia Sistémica , Humanos , Interleucina-10/metabolismo , Tirosina Quinasa c-Mer/metabolismo , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/patología , Macrófagos/metabolismo , Pulmón , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/tratamiento farmacológico , Esclerodermia Sistémica/genética , Fibrosis , Fenotipo , Proteínas Tirosina QuinasasRESUMEN
INTRODUCTION: Juvenile Sjögren's disease (jSjD) is a rare autoimmune disease characterized by exocrine gland involvement and systemic manifestations, including small vessel vasculitis and Raynaud's phenomenon (RP). We aimed to investigate the microvascular status in jSjD patients by nailfold videocapillaroscopy (NVC) and the potential correlations with clinical and serological features. METHODS: Clinical data from thirteen consecutive jSjD patients (11 females and 2 males), with a mean age of 16 ± 4 years, diagnosed before 16 years of age (mean age at diagnosis 12 ± 3) according to the 2016 American College of Rheumatology/EULAR criteria for adult SjD, were collected including age- and sex-matched healthy controls (HCs). Clinical, laboratory, and instrumental data were collected, together with NVC examination. Non-specific and specific NVC parameters were investigated, such as capillary density, capillary dilations, giant capillaries, microhaemorrhages and abnormal shapes. Associations between NVC findings and clinical/serological features were explored and analysed using parametrical and non-parametrical tests. RESULTS: Capillary density reduction correlated significantly with articular involvement (arthralgias) (p = 0.024). Microhaemorrhages correlated with lower C3 levels (p = 0.034). No specific NVC pattern for jSjD was identified, whereas abnormal capillary shapes were significantly higher in jSjD patients than HCs (p = 0.005). NVC abnormalities were not associated with SjD-specific instrumental tests (biopsy, imaging, Schirmer's test). RP was present in 8% of jSjD patients. CONCLUSIONS: The reduction of capillary density, as well as microhaemorrhages at NVC analysis, are significantly associated with some clinical aspects like articular involvement and serum biomarkers (C3 reduction). The NVC is suggested as safe and further analysis in jSjD patients.
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Enfermedades Autoinmunes , Enfermedad de Raynaud , Esclerodermia Sistémica , Síndrome de Sjögren , Masculino , Adulto , Femenino , Humanos , Niño , Adolescente , Adulto Joven , Angioscopía Microscópica/métodos , Uñas/irrigación sanguínea , Capilares/diagnóstico por imagen , Capilares/patología , Enfermedades Autoinmunes/patología , Síndrome de Sjögren/diagnóstico por imagen , Síndrome de Sjögren/patología , Enfermedad de Raynaud/patología , Esclerodermia Sistémica/patologíaRESUMEN
OBJECTIVES: Hypermobile Ehlers-Danlos Syndrome (hEDS) is a hereditary connective tissue disorder characterised by joint hypermobility, chronic musculoskeletal pain, and skin abnormalities and easy bruising. Morphological and functional microvascular status has not yet been studied in hEDS, and dermal thickness (DT) has been poorly investigated. METHODS: The aim of the study was to investigate the microvascular morphology by nailfold videocapillaroscopy (NVC), peripheral blood perfusion (PBP) by laser speckle contrast analysis (LASCA), and DT by high-frequency skin ultrasound (22 MHz probe) in adults with hEDS compared to sex- and age-matched controls. RESULTS: Microhaemorrhages were found more prevalent and the capillary number per linear millimetre at the nailfold was slightly higher in hEDS patients than in controls, as well as the NVC score for abnormal shaped capillaries was slightly lower (less abnormal shaped capillaries) in hEDS patients than in controls, even if this was not statistically significant. PBP was comparable between hEDS patients and controls. The DT resulted generally lower in hEDS patients than controls with significant values limited to feet and thorax (p=0.04). A statistically significant positive correlation was observed between the Beighton score and the score for microhaemorrhages (r=0.4, p=0.05), as well as between the Beighton score and DT (r≥0.5, p≤0.02) at the level of feet and thorax. CONCLUSIONS: Our study detected in hEDS patients a normal microvascular function at rest and a suitable capillary morphology but with increased microvascular fragility. The dermal thickness seems thinner in hEDS patients than in controls in most skin areas, with strong statistically significance at the level of feet and thorax.
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Enfermedades del Tejido Conjuntivo , Síndrome de Ehlers-Danlos , Inestabilidad de la Articulación , Adulto , Humanos , Proyectos Piloto , Síndrome de Ehlers-Danlos/complicaciones , Síndrome de Ehlers-Danlos/diagnóstico , Piel , Inestabilidad de la Articulación/diagnóstico por imagen , Inestabilidad de la Articulación/etiologíaRESUMEN
To investigate the correlations between finger microvascular morphology and function in patients with systemic sclerosis (SSc) and the status of ocular microcirculation, as detected by nailfold videocapillaroscopy (NVC), laser speckle contrast analysis (LASCA), and optical coherence tomography angiography (OCTA). The enrollment included 32 SSc patients, classified according to the 2013 ACR/EULAR criteria, and 27 sex- and age-matched healthy controls. The participants underwent comprehensive rheumatological and ophthalmological examinations, as well as NVC, LASCA, and OCTA analysis on the same day at a single center from March to October 2022. SSc patients receiving intravenous prostanoids cycles were assessed at least 1 month after infusion. Statistical analysis was conducted using Stata® 15.1. Significant direct correlations were observed between the mean capillary number (at NVC) and the mean perfusion of fingers (at LASCA) with the retinal and choroidal perfusion (at OCTA) (all p < 0.05). In addition, a significantly reduced retinal and choroidal perfusion was detected in SSc patients vs controls (all p < 0.05). Interestingly, diffuse cutaneous SSc (dcSSc) patients exhibited a lower choroidal perfusion (p = 0.03) but an increased choroidal thickness (CT) than limited cutaneous SSc patients (p < 0.001). CT was increased also in patients with positive Scl70 antibodies and with a history of digital ulcers directly correlating with disease duration (r = 0.67, p = 0.001). Finally, the combination of LASCA and OCTA parameters showed a significant discrimination capacity between SSc patients and controls, with an area under the curve of 0.80 [95% CI (0.74, 0.87)]. Peripheral microvascular damage is correlated with impaired ocular microcirculation in SSc. The increased choroidal thickness observed in dcSSc may be related to local sub-endothelial extracellular matrix deposition. The combined analysis of choroidal and fingertip perfusion offers preliminary insights that may complement traditional diagnostic methods for SSc.
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Angioscopía Microscópica , Esclerodermia Sistémica , Humanos , Tomografía de Coherencia Óptica , Perfusión , AngiografíaRESUMEN
The therapeutic landscape of rheumatoid arthritis (RA) has rapidly evolved in the last few decades. At the same time, recommendations for the management of the disease suggest to minimize glucocorticoids (GCs) use in RA patients. Major concerns are the risk of long-term adverse events and the difficulties in discontinuing GCs once initiated. However, real-world data show that up to 50% of RA patients continue to take GCs during the disease course. Adverse events of GCs usually occur after a long-term use, which can limit the generalizability of randomized controlled trials (RCTs) proving no or minimal harm. Observational studies show conflicting results regarding the safety of GSs and are subjected to a high risk of bias, including indication bias. Thus, whether or not GCs should be used in the management of RA is still a matter of debate. The main reasons to support GCs use are the ability to rapidly suppress joint inflammation while waiting for the full effect of conventional synthetic disease-modifying antirheumatic drugs (csDMARD) and the acknowledged efficacy on radiographic progression in early RA. The main reasons to avoid GCs use in RA are that their potential risks may outweigh their benefits and there is no agreement on the minimal daily dosage of GC which can be considered safe.
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Antirreumáticos , Artritis Reumatoide , Humanos , Glucocorticoides/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Antirreumáticos/efectos adversosRESUMEN
The second Special Issue of Nutrients dedicated to "Vitamin D, Immune Response, and Autoimmune Diseases" will include original data and recent achievements from authors who would like to participate in this research topic [...].
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Enfermedades Autoinmunes , Deficiencia de Vitamina D , Humanos , Vitamina D/fisiología , Vitaminas , Deficiencia de Vitamina D/complicacionesRESUMEN
Objectives: Glucocorticosteroids (GCs) are the most used anti-inflammatory and immunosuppressive drugs due to their effectiveness in managing pain and disease modification in many immune-inflammatory rheumatic diseases (IRDs). However, their use is limited because of adverse effects (AEs). Material and methods: The authors analyzed recent studies, including randomized controlled trials (RCTs), observational, translational studies and systematic reviews, providing an in-depth viewpoint on the benefits and drawbacks of GC use in rheumatology. Results: Glucocorticosteroids are essential in managing life-threatening autoimmune diseases and a cornerstone in many IRDs given their swift onset of action, necessary in flares. Several RCTs and meta-analyses have demonstrated that when administered over a long time and on a low-dose basis, GC can slow the radiographic progression in early rheumatoid arthritis (RA) patients by at least 50%, satisfying the conventional definition of a disease-modifying anti-rheumatic drug (DMARD). In the context of RA treatment, the use of modified-release prednisone formulations at night may offer the option of respecting circadian rhythms of both inflammatory response and HPA activation, thereby enabling low-dose GC administration to mitigate nocturnal inflammation and prolonged morning fatigue and joint stiffness. Long-term GC use should be individualized based on patient characteristics and minimized due to their potential AEs. Their chronic use, especially at medium/high dosages, might cause irreversible organ damage due to the burden of metabolic systemic effects and increased risk of infections. Many international guidelines recommend tapering/withdrawal of GCs in sustained remission. Treat-to-target (T2T) strategies are critical in setting targets for disease activity and reducing/discontinuing GCs once control is achieved. Conclusions: Glucocorticosteroids' use in treating IRDs should be judicious, focused on minimizing use, tapering and discontinuing treatment, when possible, to improve long-term safety. Glucocorticosteroids remain part of many therapeutic regimens, particularly at low doses, and elderly RA patients, especially with associated chronic comorbidities, may benefit from long-term low-dose GC treatment. A personalized GC therapy is essential for optimal long-term outcomes.
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Calcitriol and hydroxyderivatives of lumisterol and tachisterol are secosteroid hormones with immunomodulatory and anti-inflammatory properties. Since the beginning of the COVID-19 pandemic, several studies have correlated deficient serum concentrations of vitamin D3 (calcifediol) with increased severity of the course of SARS-CoV-2 infection. Among systemic complications, subjective (anosmia, ageusia, depression, dizziness) and objective (ischemic stroke, meningoencephalitis, myelitis, seizures, Guillain-Barré syndrome) neurological symptoms have been reported in up to 80% of severe COVID-19 patients. In this narrative review, we will resume the pathophysiology of SARS-CoV-2 infection and the mechanisms of acute and chronic neurological damage. SARS-CoV-2 can disrupt the integrity of the endothelial cells of the blood-brain barrier (BBB) to enter the nervous central system. Invasion of pro-inflammatory cytokines and polarization of astrocytes and microglia cells always in a pro-inflammatory sense together with the pro-coagulative phenotype of cerebral endothelial cells in response to both SARS-CoV-2 and immune cells invasion (immunothrombosis) are the major drivers of neurodamage. Calcitriol and hydroxyderivatives of lumisterol and tachisterol could play an adjuvant role in neuroprotection through mitigation of neuroinflammation and protection of endothelial integrity of the BBB. Dedicated studies on this topic are currently lacking and are desirable to confirm the link between vitamin D3 and neuroprotection in COVID-19 patients.
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COVID-19 , Humanos , SARS-CoV-2 , Vitamina D/farmacología , Calcitriol , Células Endoteliales , Pandemias , ErgosterolRESUMEN
OBJECTIVE: Nailfold videocapillaroscopy (NVC) allows the detection of microvascular damage in autoimmune connective tissue diseases (CTDs). The prevalence of the morphological capillary findings was retrospectively evaluated in a wide cohort of patients with Raynaud's phenomenon secondary to a CTD at the time of the first single NVC, independently from their current treatment, autoantibody profile and comorbidities. METHODS: One-thousand-one-hundred-eighty-one patients affected by CTDs were included from 2001 to 2021. The considered CTDs were systemic sclerosis (SSc), undifferentiated connective tissue disease (UCTD), mixed connective tissue disease (MCTD), dermatomyositis (DM), systemic lupus erythematosus, Sjögren's syndrome and primary antiphospholipid syndrome (aPS). The capillaroscopic parameters were distinguished between scleroderma patterns and non-scleroderma patterns. RESULTS: Giant capillaries were significantly more frequent in SSc, DM and MCTD than in other CTDs (respectively, in 73%, 73% and 61% of patients, p<0.001 when comparing each rate vs the other CTDs). The mean capillary count was significantly lower in SSc, DM and MCTD (respectively, 7.04±0.18 vs 6.5±0.75 vs 7.7±2 capillaries/linear mm) compared with the other CTDs (p<0.001 for each rate vs the other CTDs). The non-specific abnormalities of capillary morphology were significantly more frequent in SSc, MCTD and aPS (respectively, in 48%, 41% and 36% of cases, all p<0.001 vs each other CTDs). CONCLUSION: This large size sample of patients with CTDs, collected over 20 years of analysis, confirms the highest prevalence of specific capillaroscopic alterations in patients with SSc, DM and MCTD, when compared with other CTDs.
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Enfermedades Autoinmunes , Enfermedades del Tejido Conjuntivo , Enfermedad Mixta del Tejido Conjuntivo , Esclerodermia Sistémica , Humanos , Enfermedad Mixta del Tejido Conjuntivo/complicaciones , Angioscopía Microscópica/métodos , Estudios Retrospectivos , Enfermedades del Tejido Conjuntivo/complicaciones , Enfermedades del Tejido Conjuntivo/diagnóstico , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/epidemiología , Enfermedades Autoinmunes/complicaciones , Esclerodermia Sistémica/complicaciones , Esclerodermia Sistémica/diagnósticoRESUMEN
OBJECTIVE: To investigate in an unselected, systemic sclerosis (SSc) cohort if baseline laser speckle contrast analysis (LASCA) peripheral blood perfusion (PBP) measurements differ between 'early' SSc (without skin involvement, or 'limited' SSc-LSSc) and 'clinically overt' SSc (with skin involvement, limited cutaneous SSc-LcSSc and diffuse cutaneous SSc-DcSSc) in routine setting. METHODS: A group of twenty consecutive 'early' SSc patients and forty consecutive 'clinically overt' SSc patients (twenty LcSSc and twenty DcSSc) underwent clinical and LASCA examinations (to assess the peripheral blood perfusion [PBP] of both hands volar). RESULTS: No statistically significant difference in adjusted PBP was found in the 'early' versus the 'clinically overt' group (p = 0.77) when adjusted for possible confounding factors (e.g., vasoactive medication, active smoking, history of DTL and disease duration). A wide variability was noted when observing the individual datapoints of each subset. CONCLUSION: This study with an unselected SSc population in daily routine, non-research setting, showed there was no difference in adjusted PBP at baseline between 'early' SSc and 'clinically overt' SSc when corrected for possible confounding factors. Interestingly a wide variation of individual datapoints were observed in each subset, which emphasizes the heterogeneity of SSc.
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OBJECTIVE: To systematically review the literature concerning temporomandibular disorders (TMDs) in immune-mediated rheumatic diseases (IMRDs) of the adult. The temporomandibular joint (TMJ) outcomes used in clinical studies, the prevalence of TMDs in IMRDs and the risk factors for their development were qualitatively synthetized. METHODS: A literature search on PubMed Central, Embase and Cochrane Library databases was performed for studies including TMJ outcomes in IMRDs patients compared with healthy controls, other rheumatic diseases or in the assessed IMRDs patients after follow-up and treatment. Among the IMRDs of the adult, original articles investigating TMJ involvement in inflammatory polyarthritides and/or autoimmune connective tissue diseases were considered. The quality of the studies was scored using the Newcastle-Ottawa scale (NOS). RESULTS: Of the 3259 screened abstracts, 56 papers were included in the systematic review. Most of the papers (77%) investigated TMDs in rheumatoid arthritis (RA) with a prevalence of signs and symptoms varying from 8% to 70%. The risk factors for TMDs development in RA were female sex, younger age, anti-citrulline peptide autoantibodies (ACPA) positivity, higher disease activity, cervical spine involvement, cardiovascular and neuropsychiatric comorbidities. Ten papers (18%) evaluated TMDs in spondylarthritides (SpA) reporting a prevalence of symptoms and signs in 12%-80% of patients with higher TMDs prevalence in patients with radiographic spine involvement, skin psoriasis and HLADRB1×01 positivity. Among autoimmune connective tissue diseases (CTDs), systemic sclerosis (SSc) displayed the highest evidence of TMDs patient-reported outcomes (PROs) and clinical findings (20-93%), followed by systemic lupus erythematosus (SLE) in 18-85%, primary Sjogren's syndrome (24-54%) and idiopathic inflammatory myopathies (4-26%). In SSc and SLE, TMDs were more frequent in patients with higher disease activity and duration, correlating with the extent of skin fibrosis in SSc and with renal involvement in SLE. CONCLUSION: TMDs in IMRDs display a significant relevance in the rheumatological clinical practice even if often misdiagnosed. This burden is epidemiologically important in terms of PROs and clinical findings which correlate with disease activity in RA, SpA, SSc and SLE. The early recognition and multidisciplinary management of TMDs is warranted and should be aimed at hindering the TMJ structural damage maximizing the quality of life of patients.
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Artritis Reumatoide , Enfermedades Autoinmunes , Lupus Eritematoso Sistémico , Enfermedades Reumáticas , Esclerodermia Sistémica , Trastornos de la Articulación Temporomandibular , Humanos , Adulto , Femenino , Masculino , Calidad de Vida , Enfermedades Reumáticas/epidemiología , Enfermedades Reumáticas/diagnóstico , Artritis Reumatoide/psicología , Trastornos de la Articulación Temporomandibular/epidemiología , Trastornos de la Articulación Temporomandibular/etiologíaRESUMEN
Aminaphtone is a chemical drug that has been used for more than thirty years to treat a variety of vascular disorders, with good clinical results and a satisfying safety profile. In the last two decades, multiple clinical studies have reported the efficacy of the drug in different clinical scenarios of altered microvascular reactivity, describing the downregulation of adhesion molecules (i.e., VCAM, ICAM, Selectins), vasoconstrictor peptides (i.e., Endothelin-1), and pro-inflammatory cytokine expression (i.e., IL-6, IL-10, VEGF, TGF-beta) by Aminaphtone. In this review, we summarize the current knowledge concerning Aminaphtone, with particular attention to rheumatological conditions in which microvascular disfunction plays a pivotal role, such as Raynaud's phenomenon and systemic sclerosis. These latter conditions may represent a promising field of application for Aminaphtone, due to the growing pre-clinical, clinical, and instrumental reports of efficacy. However, randomized, double-blind, placebo-controlled clinical trials are lacking and are desirable.
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Evidence supporting the extra-skeletal role of vitamin D in modulating immune responses is centred on the effects of its final metabolite, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3, also known as calcitriol), which is regarded as a true steroid hormone. 1,25(OH)2D3, the active form of vitamin D, can modulate the innate immune system in response to invading pathogens, downregulate inflammatory responses and support the adaptive arm of the immune system. Serum concentrations of its inactive precursor 25-hydroxyvitamin D3 (25(OH)D3, also known as calcidiol) fluctuate seasonally (being lowest in winter) and correlate negatively with the activation of the immune system as well as with the incidence and severity of autoimmune rheumatic diseases such as rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis. Thus, a low serum concentration of 25(OH)D3 is considered to be a risk factor for autoimmune rheumatic diseases and vitamin D3 supplementation seems to improve the prognosis; moreover, long-term vitamin D3 supplementation seems to reduce their incidence (i.e. rheumatoid arthritis). In the setting of COVID-19, 1,25(OH)2D3 seems to downregulate the early viral phase (SARS-CoV-2 infection), by enhancing innate antiviral effector mechanisms, as well as the later cytokine-mediated hyperinflammatory phase. This Review provides an update of the latest scientific and clinical evidence concerning vitamin D and immune response in autoimmune rheumatic diseases and COVID-19, which justify the need for monitoring of serum 25(OH)D3 concentrations and for appropriate supplementation following clinical trial-based approaches.