RESUMEN
Psoriatic arthritis (PsA) is associated with obesity and other related comorbidities, which impose an additional burden on disease activity and response to treatment. We investigated the impact of Mediterranean diet, and exercise on the presentation and severity of PsA. Three hundred fifty-five patients with PsA (n = 279) and psoriasis (PsO) (n = 76) were included in a cross-sectional study. Demographic and clinical characteristics and dietary and exercise patterns were recorded. Patients were grouped into (i) high, moderate, and low Mediterranean diet adherence and (ii) high, medium, and low activity level. Levels of diet and exercise were correlated with disease activity indices. PsA patients had more comorbidities than their PsO counterparts (42.7% vs. 26.3%, p = .038). The majority showed a low exercise pattern (total = 71.3%, PsA = 72.4%, PsO = 67.1%). Approximately half (total = 44.2%, PsA = 43.4%, PsO = 47.4%) did not follow a Mediterranean diet. Disease Activity in Psoriatic Arthritis Score (DAPSA) (p = .004), tender (p = .003) and swollen (p = .015) joint counts, erythrocyte sedimentation rate (ESR) (p = .001), and Psoriasis Area and Severity Index (PASI) (p = .015) had an inverse correlation with exercise. Higher Mediterranean diet adherence was associated with reduced ESR (p = .056), PASI (p = .011), and body surface area (BSA) (p = .009) indices. After adjusting for body mass index (BMI), exercise retained its positive correlation with PsA disease activity, but diet showed significant correlation only with enthesitis (p = 0.015). Uptake of a Mediterranean diet and exercise have positive effects on PsA activity, independently of BMI. These findings support lifestyle recommendations to supplement conventional treatment for improvement in disease outcomes. Key points ⢠Diet and lifestyle are important influencers of health-related outcomes in PsA. ⢠In this cross-sectional study of 355 patients with psoriatic disease, we found that Med Diet and exercise improve outcomes in PsA independently of weight loss. ⢠Our results suggest that diet and lifestyle modifications should supplement conventional medical treatments.
Asunto(s)
Artritis Psoriásica , Dieta Mediterránea , Ejercicio Físico , Índice de Severidad de la Enfermedad , Humanos , Artritis Psoriásica/terapia , Masculino , Femenino , Persona de Mediana Edad , Estudios Transversales , Adulto , Anciano , Psoriasis/terapia , Psoriasis/fisiopatologíaRESUMEN
Background: Despite the development of treatments targeting T cell co-stimulation and cytokines TNF, IL-12/23, and IL-17, less than half of patients within clinical trials achieve high levels of clinical response. This fact, as well as the absence of prognostic biomarkers represents major unmet clinical needs that necessitate further investigation of the disease pathophysiology. Myeloid cells are critical components of PsA inflammatory mechanisms, being a highly prevalent immune population in biopsies of PsA target tissues, such as the skin and the synovium. Through their antigen-presenting capacity and their pro-angiogenic and pro-inflammatory properties myeloid cells could contribute to persistent inflammation in PsA leading to treatment-resistant disease. To this end, we have recently shown the expansion of monocytes in the blood of PsA patients compared to healthy subjects. Importantly, we have also identified an immature myeloid cell population in patients with highly active, refractory disease, indicating the presence of an "emergency myelopoiesis" process in PsA. Aim of the study: In this research protocol, we aim to decipher the pro-inflammatory "myeloid signature" in patients with active PsA and explore the role of immature myeloid cells in disease pathophysiology and their potential as prognostic biomarkers. Methods: To address this, we will isolate and analyse monocytes and immature myeloid cells from PsA patients -before and after a 6-month treatment course- focusing on differences between responders and non-responders. In this context, we will perform a thorough phenotypic and functional analysis of these cells, identify their expression signature in an already established whole blood RNA-seq dataset and investigate their presence in target tissues, such as the skin and synovial fluid. Anticipated benefits: This study will elucidate the role of myeloid cells in disease propagation by further defining the involvement of immature myeloid cells in PsA.
RESUMEN
Giant cell arteritis (GCA) is a large-vessel vasculitis that affects cranial and extra-cranial arteries. Extra-cranial GCA presents mainly with non-specific symptoms and the differential diagnosis is very broad, while the cranial form has more typical clinical picture and physicians have a lower threshold for diagnosis and treatment. Although temporal artery biopsy (TAB) has an established role, ultrasound (US) is being increasingly used as the first-line imaging modality in suspected GCA. Vasculitides (especially ANCA-associated), hematological disorders (mainly amyloidosis), neoplasms, infections, atherosclerosis and local disorders can affect the temporal arteries or might mimic the symptoms of cranial GCA and produce US and TAB findings that resemble those of temporal vasculitis. Given that prompt diagnosis is essential and proper treatment varies significantly among these diseases, in this review we aimed to collectively present disorders that can masquerade cranial GCA.
Asunto(s)
Arteritis , Arteritis de Células Gigantes , Arterias/patología , Biopsia , Arteritis de Células Gigantes/patología , Humanos , Arterias Temporales/diagnóstico por imagen , Arterias Temporales/patología , UltrasonografíaRESUMEN
Background: An interplay between immune cells and resident skin and joint stromal cells is implicated in psoriatic arthritis (PsA), yet the mechanisms remain elusive with a paucity of molecular biomarkers for activity and response. Combined transcriptomic and immunophenotypic analysis of whole blood and skin fibroblasts could provide further insights. Methods: Whole blood RNA-seq was performed longitudinally in 30 subjects with PsA at the beginning, one and six months after treatment, with response defined at six months. As control groups, 10 healthy individuals and 10 subjects with rheumatoid arthritis (RA) were recruited combined with public datasets from patients with psoriasis (PsO) and systemic lupus erythematous (SLE). Differential expression analysis and weighted gene co-expression network analysis were performed to identify gene expression signatures, while deconvolution and flow cytometry to characterize the peripheral blood immune cell profile. In a subset of affected and healthy individuals, RNA-seq of skin fibroblasts was performed and subjected to CellChat analysis to identify the blood-skin fibroblast interaction network. Results: PsA demonstrated a distinct "activity" gene signature in the peripheral blood dominated by TNF- and IFN-driven inflammation, deregulated cholesterol and fatty acid metabolism and expansion of pro-inflammatory non-classical monocytes. Comparison with the blood transcriptome of RA, PsO, and SLE revealed a "PsA-specific signature" enriched in extracellular matrix remodeling. This was further supported by the skin fibroblast gene expression profile, displaying an activated, proliferating phenotype, and by skin-blood interactome analysis revealing interactions with circulating immune cells through WNT, PDGF and immune-related semaphorins. Of note, resistance to treatment was associated with upregulation of genes involved in TGFß signaling and angiogenesis and persistent increase of non-classical monocytes. Differentially expressed genes related to platelet activation and hippo signaling discriminated responders and non-responders as early as one month after treatment initiation. Conclusion: Transcriptome analysis of peripheral blood and skin fibroblasts in PsA reveals a distinct disease activity signature and supports the involvement of skin fibroblasts through their activation and interaction with circulating immune cells. Aberrant TGFß signaling and persistently increased non-classical monocytes characterize treatment-resistant PsA, with pro-inflammatory pathways related to platelet activation and Hippo signaling predicting early response to treatment.
Asunto(s)
Artritis Psoriásica , Artritis Reumatoide , Lupus Eritematoso Sistémico , Psoriasis , Semaforinas , Artritis Psoriásica/tratamiento farmacológico , Artritis Psoriásica/genética , Biomarcadores/metabolismo , Ácidos Grasos/metabolismo , Fibroblastos/metabolismo , Perfilación de la Expresión Génica , Humanos , Lupus Eritematoso Sistémico/metabolismo , Psoriasis/metabolismo , Semaforinas/metabolismo , Transcriptoma , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
Background: The demyelinating syndromes of the central nervous system (CNS) that occur in the context of systemic lupus erythematosus (SLE) may represent a manifestation of neuropsychiatric lupus (NPSLE) or an overlap of SLE and multiple sclerosis (MS). The differential diagnosis between the two entities has important clinical implications because the therapeutic management differs. Objectives: To characterize CNS demyelinating syndromes in a large SLE cohort as neuropsychiatric SLE (NPSLE) or SLE-MS overlap using a multidisciplinary approach and existing diagnostic (for MS) and classification criteria (for SLE). Methods: Patients from the "Attikon" lupus cohort (n = 707) were evaluated for demyelinating syndromes. Clinical, laboratory, and neuroimaging data were recorded for each patient. Following multidisciplinary evaluation and application of criteria, the demyelinating syndrome was attributed to either SLE or MS. Patients with transverse myelitis were not included in this study. Results: We identified 26 patients with demyelinating syndromes (3.7%). Of them, 12 were diagnosed as primary SLE-demyelination (46.2%) and 14 as overlap SLE-MS (53.8%). The two groups did not differ with respect to rheumatologic and neurologic manifestations or autoantibodies. SLE patients with demyelination manifested mild extra-CNS disease mainly involving joints and skin, while severe non-CNS manifestations were rare. However, these patients were less likely to have elevated IgG index (OR 0.055 95% CI: 0.008-0.40) and positive oligoclonal bands (OR 0.09 95% CI: 0.014-0.56), as well as brain lesions in the spinal cord, infratentorial, periventricular, and juxtacortical regions. A single brain region was affected in 9 patients with SLE-demyelination (75%), while all patients with MS-SLE had multiple affected brain regions. MS-SLE overlap was associated with an increased likelihood of neurologic relapses (OR 18.2, 95% CI: 1.76-188), while SLE-demyelination patients were less likely to exhibit neurological deficits (EDSS >0) at the last follow-up visit (50 vs. 78.6% in SLE-MS, respectively). Conclusions: Demyelination in the context of SLE follows a more benign course compared to a frank SLE-MS overlap. Extension of follow-up will ascertain whether patients with SLE-demyelination evolve to MS, or this is a bona fide NPSLE syndrome.
RESUMEN
-Omic technologies represent a novel approach to unravel ill-defined aspects of psoriatic arthritis (PsA). Large-scale information can be acquired from analysis of affected tissues in PsA via high-throughput studies in the domains of genomics, transcriptomics, epigenetics, proteomics and metabolomics. This is a critical overview of the current knowledge of -omics in PsA, with emphasis on the pathophysiological insights of diagnostic and therapeutic relevance, the advent of novel biomarkers and their potential use for precision medicine in PsA.
Asunto(s)
Artritis Psoriásica , Artritis Psoriásica/diagnóstico , Artritis Psoriásica/genética , Artritis Psoriásica/terapia , Genómica , Humanos , Metabolómica , Medicina de Precisión , ProteómicaRESUMEN
Background: Real world evidence data regarding secukinumab (SEC) use in biologic-experienced patients with psoriatic arthritis (PsA) are scarce. Objectives: To assess the real life survival, safety and efficacy of SEC in biologic-experienced patients with PsA. Methods: All biologic-experienced PsA patients treated with SEC in 2 University Rheumatology Units were included (3/2016-12/2018). Patients' and disease characteristics were recorded at baseline and during SEC therapy. Results: 75 patients were included; 76% were females with a mean age of 53.9 years, median disease duration of 6.7 years and median SEC treatment duration of 11.1 months. At baseline, 97% had peripheral arthritis, 42% axial involvement, 22% enthesitis, and 12% dactylitis. Regarding previous biologic exposure, 48 (64%) had been exposed to anti-tumor necrosis factor (TNF) agents only, 5 (7%) to the interleukin (IL)-12/23 inhibitor (Ustekinumab-UST) only while 22 (29%) both to anti-TNFs and UST. Fifty-three percent received SEC in combination with non-biologics and 35% with glucocorticoids, respectively. During follow-up, statistically significant improvement in different disease activity indices were noted (DAS28-CRP, DAPSA, BASDAI). SEC survival rate at the end of follow-up was 64% (48/75), without difference between patients exposed to anti-TNFs only (67%) vs. anti-TNFs and UST (68%) as well as to 1 vs. ≥2 anti-TNFs. The rate of serious adverse events and serious infections during follow-up was 4.8 and 1.2/100 patient-years, respectively. Discussion: In real life, in biologic-experienced patients with PsA, SEC displayed a high retention rate, regardless of the type, and number of previous biologics (anti-TNFs ± anti-IL12/23), without significant side effects.
RESUMEN
BACKGROUND/AIM: Epithelioid angiomyolipoma of the liver is a rare benign mesenchymal tumor that usually presents in adult female patients. It most frequently occurs in the kidney, with the liver being the second most common site of involvement. Angiomyolipoma belongs to a family of tumors arising from perivascular epithelioid cells, but in rare cases may also have cystic features. We report our experience via the first case of hepatic angiomyolipoma treated by laparoscopic approach. PATIENTS AND METHODS: We present the case of a 50-year-old female patient complaining of abdominal pain. Abdominal ultrasound (US) and Magnetic Resonance Imaging (MRI) revealed a 5 × 3 cm mass located in the left liver lobe. The tumor was resected with a laparoscopic approach. Microscopic examination of the tumor revealed hepatic angiomyolipoma. RESULTS: Twenty-seven months postoperatively, the patient remains fit and healthy. CONCLUSION: Angiomyolipoma can be removed by laparoscopy.