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VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic) syndrome is characterized by heterogeneous clinical manifestations. Due to the inflammatory nature of this condition, 18-FDG-PET (18-fluorodeoxyglucose-positron emission tomography) might be used to diagnose and monitor the disease. However, no data are available about the most common findings of PET imaging in this disease. For this reason, we summarised all the available reports of patients with VEXAS who underwent at least one PET scan and described 8 additional patients' PET from our centres. Overall, we described 35 patients' PET findings. All patients were male, with a median age of 70 years. The most frequent hypermetabolic sites on PET scans were the bone marrow (77.1%), lymph nodes (35.3%), lungs (28.6%), spleen and large vessels (22.9%), and cartilage (20%). Six patients underwent a PET scan 2.7 ± 1.5 years before VEXAS diagnosis, showing nonspecific uptake in the bone marrow. Four patients had a follow-up PET scan, showing a decrease or a disappearance of the previously identified hypermetabolic areas. In conclusion, although no specific uptake site has been found for VEXAS syndrome, PET imaging could help detect inflammatory foci that are not clinically evident. In addition, high metabolic activity in bone marrow might precede the clinical onset of the disease, shedding light on the pathogenesis of VEXAS.

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BACKGROUND: Rheumatoid arthritis (RA) is characterized by bone loss. It is unclear whether JAK inhibitors can attenuate bone loss in RA by modulating bone metabolism. The main objective of our study is to investigate the effects of tofacitinib on serum levels of bone turnover markers and modulators. Secondary objectives were to assess changes in bone mineral density (BMD), metacarpal index, bone erosions. METHODS: We conducted a prospective observational study on patients with active RA failure to bDMARDs or tsDMARDs initiating treatment with tofacitinib. We measured at baseline and after 1, 2, 3, 6, 9 and 12 months: serum bone turnover markers (CTX, P1nP, B-ALP), bone modulators (Dkk-1, sclerostin, vitamin D, PTH, OPG and RANKL), BMD and radiographic parameters (Sharp van der Heijde score [SvdH], bone health index [BHI] and metacarpal index [MCI]). RESULTS: 30 patients were enrolled in the study of whom 21 completed the study through month 12. Tofacitinib was clinically effective by suppressing DAS28-CRP. Glucocorticoids daily dose significantly decreased from baseline. We found a negative correlation between pre-study cumulative and daily dose of glucocorticoids and baseline B-ALP serum levels (r -0.592, p 0.012). Sclerostin serum levels increased significantly during the study period, while P1nP and B-ALP (markers of bone formation) decreased significantly. BMD levels, BHI, MCI and SvdH score did not change. CONCLUSION: Treatment with tofacitinib was associated with a significant increase in sclerostin serum levels and a parallel decrease in markers of bone formation. However, no significant bone loss was observed.

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BACKGROUND: Glucocorticoid sparing in rheumatoid arthritis (RA) treatment is crucial to minimizing adverse effects associated with long-term use. Janus kinase inhibitors (JAKi) could potentially offer a more potent glucocorticoid-sparing effect than biological Disease-Modifying Antirheumatic Drugs (bDMARDs). MATERIAL AND METHODS: This is a single-center retrospective analysis of RA patients treated with JAKi or bDMARDs. Glucocorticoid tapering, rescue therapy and discontinuation were analyzed through mixed-effects models, Poisson regression, and multivariable logistic regression, respectively, adjusting for baseline disease activity, demographic factors, and treatment line. RESULTS: A total of 716 RA patients treated with JAKi (n = 156) or bDMARDs (n = 560) were evaluated. JAKi treatment was associated with a more rapid reduction in glucocorticoid dose within the first 6 months and 60% higher odds of discontinuation compared with bDMARDs (adjusted odds ratio 1.63, 95% CI 1.02-2.60, p 0.039). Despite a higher baseline glucocorticoid dose, over 50% of JAKi-treated patients discontinued glucocorticoids after 12 months, vs ∼40% for bDMARDs. The need for glucocorticoid rescue therapy was significantly higher in the bDMARD group (rate ratio 2.66 (95% CI, 1.88-3.74)). CONCLUSION: Our findings indicate that JAK inhibitors facilitate more rapid glucocorticoid tapering compared with bDMARDs in RA patients. These results underscore the potential of JAK inhibitors to reduce long-term glucocorticoid exposure, highlighting their value in RA management strategies, including minimizing glucocorticoid-related adverse effects.

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Hypereosinophilic syndromes (HES) represent a group of rare dis-immune conditions characterized by blood hyper-eosinophilia and eosinophilic related burden. Especially the idiopathic subtype (I-HES) is particularly difficult to diagnose because of its heterogeneous clinical presentation, the lack of specific findings on physical exam, lab tools, and imaging informative enough to unequivocally confirm the diagnosis and the overlap with other entities, including eosinophilic organ-diseases or systemic dis-immune conditions other than I-HES (from atopy to eosinophilic granulomatosis with polyangiitis [EGPA], the last often extremely difficult to distinguish from HES). Taken together, all the features mentioned above account for an extremely difficult early recognition HES and on-time referral to a specialized centre. The referral itself is challenging due to a not univocal specialist identification, because of the variability of physicians managing HES in different settings (including allergist/clinical immunologist, haematologist, internal medicine doctors, pulmonologist, rheumatologist). Furthermore, the approach in terms of personalized treatment identification and follow-up plan (timing, organ assessment), is poorly standardized. Further translational and clinical research is needed to address the mentioned unmet needs, but on practical grounds increasing the overall clinicians' awareness on HES and implementing healthcare pathways for HES patients represent a roadmap that every clinician might try to realize in his specific setting. The present review aims at providing an overview about the current challenges and unmet needs in the practical approach to HES and rare hypereosinophilic allergo-immunological diseases, including a proposal for an innovative multidisciplinary organizational model.

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OBJECTIVE: The aim of this study was to investigate the association between exposure to particulate matter with an aerodynamic diameter ≤10 µm (PM10) and the development of giant cell arteritis (GCA) and its ischemic complications. METHODS: This was case-crossover study on consecutive patients who received a diagnosis of GCA in three hospitals in northern Italy between 2013 and 2021. The PM10 hourly and daily average concentrations, collected in the Italian monitoring network and archived by Istituto Superiore per la Protezione e la Ricerca Ambientale, were determined using European reference. We used a Bayesian hierarchical model to determine patients' daily exposures to them. We employed conditional logistic regression to estimate the effect of exposure on GCA symptoms onset or ischemic complications. RESULTS: We included 232 patients. A positive association was observed between exposure to PM10 and GCA risk, with an incremental odd of 27.1% (95% confidence interval 5.8-52.6) for every 10-µg/m3 increase in PM10 concentration within a 60-day period. We did not find any significant association for shorter periods or with ischemic complications. Subgroup analysis found a significantly higher incremental risk at a 60-day lag for patients ≥70 years old. Comparing patients who were chronically exposed to high PM10 levels (26.9 ± 13.8 µg/m3) to those who were not (11.9 ± 7.9 µg/m3) revealed that only in the former group was there an association between GCA onset and increased PM10 levels in the preceding 60 days. CONCLUSION: Exposure to environmental PM10 in the preceding 60 days seems to be associated with an increased risk of developing GCA, especially in older individuals with prolonged exposure to high levels of air pollution.

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Objectives: This study aims to evaluate in a real-life Italian multicenter cohort of axial spondyloarthritis (axSpA) (1) the 4-year effectiveness and safety of secukinumab, (2) the drug retention rate (DRR), and (3) the impact of the line of bDMARDs treatment, subtype of axSpA, and sex on achieving low disease activity (LDA) and very low disease activity (VLDA). Methods: Consecutive axSpA patients receiving secukinumab between 2016 and 2023 were prospectively evaluated. Data on disease characteristics, previous/ongoing treatments, comorbidities, and follow-up duration were collected. Treatment response was evaluated at 6 and 12 months after initiation and yearly up to 48 months (T48). DRR and effectiveness outcomes were evaluated according to bDMARDs treatment, axSpA subtype, and sex. Infections and adverse events (AEs) were recorded. Results: We enrolled 272 patients (48.2% male; median age, 51; 39.7% HLA-B27+; 40.4% nr-axSpA), of whom 30.9% were naïve to secukinumab. Overall, secukinumab yielded improvement in effectiveness outcomes; the naïve patients maintained lower disease activity vs. the non-naïve ones. At T48, the LDA and VLDA rates were higher in naïve patients and in male individuals. Treatment was discontinued in 104 patients due to primary/secondary loss of effectiveness and in 34 patients due to AEs. The DRR at T48 was 67.4% in the whole population, regardless of treatment line, axSpA subtype, and sex. Conclusions: Secukinumab was safe and effective in all axSpA patients irrespective of treatment line, disease subtype, and sex. The patients achieved sustained 4-year remission and DRR.

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Anticuerpos Monoclonales Humanizados , Espondiloartritis Axial , Humanos , Masculino , Femenino , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Persona de Mediana Edad , Italia , Adulto , Resultado del Tratamiento , Espondiloartritis Axial/tratamiento farmacológico , Antirreumáticos/uso terapéutico , Antirreumáticos/efectos adversos , Estudios Prospectivos , Estudios de Cohortes

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BACKGROUND: A score to predict the association between unexplained osteoporosis and an underlying systemic Mastocytosis (SM) is lacking. OBJECTIVE: This study aimed at identifying criteria able to predict the diagnosis of SM without skin involvement and provide an indication for bone marrow (BM) assessment. METHODS: We included 139 adult patients with unexplained osteoporosis and suspected SM. After BM evaluation, 63 patients (45.3 %) were diagnosed with SM, while the remaining 76 patients (54.7 %) negative for clonal mast cell (MC) disorders, constituted our control group. Univariate and multivariate analysis identified three independent predictive factors: age (<54 years: +1 point, >64 years: -1 point), serum basal tryptase (sBT) levels >19 ng/mL (+2 points) and vertebral fractures (+2 points). RESULTS: These variables were used to build the OSTEO-score, able to predict the diagnosis of SM before BM assessment with a sensitivity of 73.5 % and a specificity of 67.1 %. Patients with a score < 3 had a lower probability of having SM compared to patients with a score ≥ 3 (28.5 % and 71.4 %, respectively, p < 0.0001). When sBT levels were corrected for the presence of hereditary alpha-tryptasemia (HαT) using the BST calculater (https://bst-calculater.niaid.nih.gov/) recently published [1,2], the sensitivity of ΗαT-adjusted OSTEO-score increased to 87.8 %, and the specificity reached 76.1 %. Also, the positive predictive value of a score ≥ 3 increased to 85.2 %. CONCLUSIONS: Further studies are needed to validate these results and characterize the role of tryptase genotyping in patients with unexplained osteoporosis in reducing the risk of misdiagnosing patients with SM. Our proposed scoring model allows the identification of patients with the highest probability of having SM, avoiding unnecessary BM studies.

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Mastocitosis Sistémica , Osteoporosis , Humanos , Mastocitosis Sistémica/complicaciones , Mastocitosis Sistémica/sangre , Mastocitosis Sistémica/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Anciano , Adulto , Triptasas/sangre , Médula Ósea/patología

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Data on the effectiveness of denosumab on osteoporosis after kidney transplantation are limited. We investigated the long-term bone mineral density (BMD) changes in kidney transplant recipients (KTRs) treated with denosumab compared to untreated KTRs. We enrolled KTRs treated with denosumab 60 mg/6 months for 4 years. An untreated group of sex and age-matched KTRs with a 1:1 ratio was included. The primary outcome was BMD changes assessed by Dual-energy X-ray Absorptiometry over 4 years. Data on serum creatinine, alkaline phosphatase (ALP), parathyroid hormone, and 25-hydroxyvitamin D were collected. All patients received oral cholecalciferol and calcium supplementation. 23 denosumab-treated KTRs were enrolled, and 23 untreated KTRs. The median time from transplant to the start of denosumab was 4 years (range 0:24). The denosumab group showed a significant increase from baseline in BMD at the lumbar spine (LS) (9.0 ± 10.7%, p < 0.001), and total hip (TH) (3.8 ± 7.9%, p = 0.041). The untreated group showed a significant decrease at all sites (- 3.0 ± 7%, p = 0.041 at the LS; - 6.3 ± 9.2%, p = 0.003 at the TH; - 6.7 ± 9.3%, p = 0.003 at the FN). The between-group differences in percent BMD changes were statistically significant at all sites. Similar results were found for the respective Z-scores. The ALP serum levels significantly decreased from baseline only in the denosumab group, with a significant between-group difference (p = 0.032). No significant differences in serum creatinine, hypocalcaemic events or acute graft rejection rates were observed. Four years of denosumab therapy were associated with increased BMD in KTRs, while untreated KTRs showed significant BMD losses at all sites.

Asunto(s)

Conservadores de la Densidad Ósea , Densidad Ósea , Denosumab , Trasplante de Riñón , Humanos , Denosumab/uso terapéutico , Densidad Ósea/efectos de los fármacos , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Conservadores de la Densidad Ósea/uso terapéutico , Adulto , Anciano , Osteoporosis/tratamiento farmacológico , Absorciometría de Fotón

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Background: Subjects with a fragility fracture have an increased risk of a new fracture and should receive effective strategies to prevent new events. The medium-term to long-term strategy should be scheduled by considering the mechanisms of action in therapy and the estimated fracture risk. Objective: A systematic review was conducted to evaluate the sequential strategy in patients with or at risk of a fragility fracture in the context of the development of the Italian Guidelines. Design: Systematic review and meta-analysis. Data sources and methods: PubMed, Embase, and the Cochrane Library were investigated up to February 2021 to update the search of a recent systematic review. Randomized clinical trials (RCTs) that analyzed the sequential therapy of antiresorptive, anabolic treatment, or placebo in patients with or at risk of a fragility fracture were eligible. Three authors independently extracted data and appraised the risk of bias in the included studies. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Effect sizes were pooled in a meta-analysis using fixed-effects models. The primary outcome was the risk of refracture, while the secondary outcome was the bone mineral density (BMD) change. Results: In all, 17 RCTs, ranging from low to high quality, met our inclusion criteria. A significantly reduced risk of fracture was detected at (i) 12 or 24 months after the switch from romosozumab to denosumab versus placebo to denosumab; (ii) 30 months from teriparatide to bisphosphonates versus placebo to bisphosphonates; and (iii) 12 months from romosozumab to alendronate versus the only alendronate therapy (specifically for vertebral fractures). In general, at 2 years after the switch from anabolic to antiresorptive drugs, a weighted BMD was increased at the lumbar spine, total hip, and femoral neck site. Conclusion: The Task Force formulated recommendations on sequential therapy, which is the first treatment with anabolic drugs or 'bone builders' in patients with very high or imminent risk of fracture.

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A systematic review to evaluate the sequential therapy of antiresorptive (denosumab and bisphosphonate, such as alendronate, minodronate, risedronate, and etidronate), anabolic treatment (such as romosozumab, teriparatide), or placebo in patients with or at risk of a fragility fracture in the context of the development of the Italian Guidelines Subjects with previous fragility fractures should promptly receive effective strategies to prevent the risk of subsequent events. Indeed, patients with a fragility fracture have a doubled risk of a new fracture. For this reason, it is essential to provide adequate sequential therapy based on the mechanisms and the rapidity of action. A systematic review was performed to identify the sequential strategy in patients at high- or imminent-risk of (re)fracture and to support the Panel of the Italian Fragility Fracture Guideline in formulating recommendations. Our systematic review included seventeen studies mostly focused on women and enabled us to strongly recommend the anabolic drugs as first-line treatment. Specifically, for the sequential therapy from anabolic to antiresorptive treatment, there was a significant reduction in the risk of different types of fractures after the switch from romosozumab to denosumab versus placebo to denosumab. These findings were confirmed at 24 months after the switch. Considering the sequential treatment from antiresorptive to anabolic medications, there was a decreased risk of fracture 12 months after the switch from placebo to teriparatide versus bisphosphonate or antiresorptive to teriparatide. Moreover, a greater bone mineral density increase after the switch from anabolic to antiresorptive medications was shown in the lumbar spine, total hip, and femoral neck. The results of this systematic review and meta-analysis confirm that initial treatment with anabolic drugs produces substantial bone mineral density improvements, and the transition to antiresorptive drugs can preserve or even amplify the acquired benefit. These findings support the choice to treat very high-risk individuals with anabolic drugs first, followed by antiresorptive drugs.

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Background: Optimization of sequential and combination treatment is crucial in shaping long-term management of postmenopausal osteoporosis (OP). Methods: We conducted a 6-month prospective observational study on postmenopausal women with severe OP receiving treatment with romosozumab either alone (in patients naïve to treatment) or in combination with ongoing long-term denosumab (>2 years) or continuing ongoing denosumab alone (>2 years). We collected serum samples for bone turnover markers, bone modulators, and calcium phosphate metabolism at baseline, month 3 and month 6. BMD was assessed at baseline and after 6 months. Results: Fifty-two postmenopausal women with OP were included in the study. Nineteen received romosozumab alone, 11 received romosozumab combined to ongoing denosumab, and 22 continued denosumab alone. BMD increased significantly at all sites at 6 months of follow-up in the romosozumab alone group (femoral neck +8.1%, total hip +6.8%, and lumbar spine +7.9%). In contrast, BMD increased significantly only at lumbar spine in the combination group (+7.2%) and in the denosumab group (+1.5%). P1nP increased significantly in romosozumab groups at month 3 (+70.4% in romosozumab alone group and +99.1% in combination group). Sclerostin levels increased steeply in both romosozumab groups, and Dkk1 did not change. Conclusion: Romosozumab added to ongoing denosumab resulted in an increase in P1nP and lumbar spine BMD, but not in femoral neck BMD. For patients on denosumab, using romosozumab as an additional treatment appeared to be useful in terms of bone formation markers and spine BMD vs denosumab alone. Further randomized controlled trials, possibly powered to fracture outcomes, are needed to confirm our results.

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Objectives: An increased number of elderly individuals affected by rheumatoid arthritis (RA) has been reported, including both patients with RA onset in advanced age and patients aged with the disease. In this registry-based study, we aimed to analyze the retention rate and cause of discontinuation of biologic (b) and targeted synthetic (ts)-disease-modifying anti-rheumatic drugs (DMARDs) in RA patients over 65 year old. Methods: RA patients enrolled in the Italian GISEA registry and starting a b- or a ts-DMARD over 65 years of age were included. Demographic, clinical, serologic, and therapeutic features were collected. Results: A total of 1,221 elderly RA patients were analyzed (mean age 71.6 ± 5.2 years). RA was diagnosed before 65 years in 72.5% of cases, a 60.6% of patients experienced a previous b- or ts-DMARD. In patients older than 65 initiating a new b- or ts-DMARDS, tumor necrosis factor alpha inhibitors (TNFi) were prescribed in 29.6% of patients, abatacept in 24.8%, anti-interleukin 6 receptor antagonists (anti-IL6R) in 16.3%, Janus kinases inhibitors (JAKi) in 24.9%, and rituximab in 4.4%. The main causes of discontinuation were primary or secondary inadequate responses (66.1%). The median retention rate for all treatments was 181.3 weeks. A statistically higher retention rate was observed for abatacept when compared to TNFi (p = 0.02), JAKi (p < 0.001), and anti-IL6R (p < 0.001), and for TNFi vs. JAKi (p = 0.013). Conclusion: We described, in a real-life setting, elderly RA patients treated with a biologic or a ts-DMARD in Italy. Loss of efficacy was the main cause of discontinuation, and the DMARD safety profile suggests that age does not contraindicate their use. Our study reinforced that the control of disease activity is mandatory.

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Dual-energy X-ray absorptiometry (DXA) represents the gold standard for measuring bone mineral density (BMD). However, its size and bulkiness limit its use in mass screening. Portable and easily accessible instruments are more suitable for this purpose. We conducted a study to assess the repeatability, sensitivity, accuracy, and validation of a new ultrasound densitometer for the calcaneus (OsteoSys BeeTLe) compared to standard DXA. BMD (g/cm2) was measured at the femoral and lumbar spine levels using DXA (Discovery Acclaim (Hologic, Waltham, MA, USA) or Lunar Prodigy (GE Healthcare, Madison, WI, USA) devices). Bone Quality Index (BQI, a dimensionless measure of bone quality derived from measures of SOS [Speed Of Sound] and BUA [broadband ultrasound attenuation]) was measured with OsteoSys BeeTLe. The Bland-Altman test and simple linear regression were used to evaluate the association between values measured with the two instruments. Additionally, the ability of the T-score calculated with BeeTLe to identify patients with previous osteoporotic fractures was tested using ROC curves. A total of 201 patients (94.5% females) with a mean age of 62.1 ± 10.2 were included in the study. The BeeTLe instrument showed a coefficient of variation (CV, in 75 repeated measurements) of 1.21%, which was not statistically different from the CV of DXA (1.20%). We found a significant association between BQI and BMD at the femoral neck (r2 = 0.500, p < 0.0001), total femur (r2 = 0.545, p < 0.0001), and lumbar spine (r2 = 0.455, p < 0.0001). T-scores bias were 0.215 (SD 0.876), 0.021 (SD 0.889) and 0.523 (SD 0.092), for femoral neck, total hip and lumbar spine respectively. AUC for discriminating fracture and non-fractured patients were not significantly different with OsteoSys BeeTLe and standard DXA. In this preliminary study, BeeTLe, a new point-of-care ultrasound densitometer, demonstrated good repeatability and performance similar to DXA. Therefore, its use can be proposed in screening for osteoporosis.

Asunto(s)

Calcáneo , Fracturas Osteoporóticas , Femenino , Humanos , Persona de Mediana Edad , Anciano , Masculino , Absorciometría de Fotón , Calcáneo/diagnóstico por imagen , Sistemas de Atención de Punto , Sensibilidad y Especificidad , Densidad Ósea , Ultrasonografía

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Objectives: The primary objective of this study was the translation and validation of the ANCA-associated vasculitis patient-reported outcome (AAV-PRO) questionnaire into Italian, denoted as AAV-PRO_ita. The secondary objective was to evaluate the impact of ANCA-associated vasculitis (AAV) on quality of life (QoL) and work impairment in a large cohort of Italian patients. Methods: The study design took a prospective cohort study approach. First, the AAV-PRO was translated into Italian following the step guidelines for translations. The new AAV-PRO_ita questionnaire covered three disease domains: organ-specific and systemic symptoms and signs; physical function; and social and emotional impact. Second, Italian-speaking AAV patients were recruited from 17 Italian centres belonging to the Italian Vasculitis Study Group. Participants completed the AAV-PRO_ita questionnaire at three time points. Participants were also requested to complete the work productivity and activity impairment: general health questionnaire. Results: A total of 276 AAV patients (56.5% women) completed the questionnaires. The AAV-PRO_ita questionnaire demonstrated a good internal consistency and test-retest reliability. Female AAV patients scored higher (i.e. worse) in all thee domains, especially in the social and emotional impact domain (P < 0.001). Patients on glucocorticoid therapy (n = 199) had higher scores in all domains, especially in the physical function domain (P < 0.001), compared with patients not on glucocorticoid therapy (n = 77). Furthermore, patients who had at least one relapse of disease (n = 114) had higher scores compared with those who had never had one (n = 161) in any domain (P < 0.05). Finally, nearly 30% of the patients reported work impairment. Conclusion: The AAV-PRO_ita questionnaire is a new 29-item, disease-specific patient-reported outcome measuring tool that can be used in AAV research in the Italian language. Sex, glucocorticoids and relapsing disease showed the greatest impact on QoL.

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Gota , Nefrolitiasis , Tomografía Computarizada por Rayos X , Ácido Úrico , Humanos , Gota/diagnóstico por imagen , Nefrolitiasis/diagnóstico por imagen , Masculino , Imagenología Tridimensional , Persona de Mediana Edad

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OBJECTIVES: Fatigue is a common comorbidity in patients with axial spondyloarthritis (axSpA), often reported also by those in clinical remission or with moderate disease activity. The aim of this study is to assess the prevalence of fatigue in patients with axSPA, and to investigate possible non-disease-related determinants, with a special focus on depression. METHODS: Patients with axSpA were assessed using the Chalder's Fatigue Questionnaire (CFQ) for fatigue, and the depression subscale of the Hospital Anxiety and Depression Scale (HADS-D) for depression. Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Functional Index (BASFI) and Health Assessment Questionnaire (HAQ) were also used to assess disease activities and disability. Univariate and multivariate linear regressions were performed to identify possible predictors of fatigue. RESULTS: Out of 119 patients, 53 (44.5%) had fatigue. Patients with fatigue had higher HADS-D, ASDAS, BASFI, HAQ scores. HADS-D was predictive of CFQ score in univariate and multivariate regressions for total CFQ, and for mental and physical subscales. The correlation between HADS-D and CFQ total score was statistically significant also when taking into consideration only patients in clinical remission and with moderate disease activity. Depressed patients had higher CFQ score compared to non-depressed ones, and did not show any difference in CFQ scores when stratified for disease activity or systemic inflammation. CONCLUSIONS: The study found correlation between fatigue and disease activity and depression in patients with axSpA. These findings suggest that depression could represent the major determinant of fatigue in patients with axSpA, independently of clinical activity.

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Espondiloartritis Axial , Depresión , Fatiga , Índice de Severidad de la Enfermedad , Humanos , Masculino , Femenino , Fatiga/fisiopatología , Fatiga/diagnóstico , Fatiga/etiología , Fatiga/psicología , Fatiga/epidemiología , Depresión/epidemiología , Depresión/psicología , Depresión/diagnóstico , Depresión/etiología , Adulto , Persona de Mediana Edad , Espondiloartritis Axial/diagnóstico , Espondiloartritis Axial/epidemiología , Espondiloartritis Axial/psicología , Espondiloartritis Axial/complicaciones , Espondiloartritis Axial/fisiopatología , Prevalencia , Encuestas y Cuestionarios , Evaluación de la Discapacidad , Comorbilidad , Análisis Multivariante , Factores de Riesgo , Modelos Lineales , Estudios Transversales

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OBJECTIVES: We aimed to investigate the effectiveness of tumour necrosis factor inhibitors (TNFi), anti-interleukin-17 or interleukin-12/23 monoclonal antibodies (anti-IL) on comorbidities in a cohort of patients with spondyloarthritis (SpA), using an average treatment effect (ATE) analysis. METHODS: SpA patients from the multicentre Italian GISEA Registry were divided into groups according to pharmacological exposure: no treatment (G0), TNFi (G1) and non-responders to TNFi switched to anti-IL (G2). In each group, we recorded the prevalence and incidence of infectious, cardiopulmonary, endocrinological, gastrointestinal, oncologic, renal and neurologic comorbidities. Each comorbidity was then fitted for ATE and baseline features were evaluated for importance. RESULTS: The main findings of this study comprising 4458 SpA patients relate to cancer, other gastrointestinal diseases (OGID) and fibromyalgia. ATE showed no increased risk of solid cancer in G1 (0.42 95% CI 0.20-0.85) and G2 (0.26 95% CI 0.08-0.71) vs. G0, with significantly higher incidence in G0 (14.07/1000 patient-years, p=0.0001). Conversely, a significantly higher risk of OGID and fibromyalgia was found in G1 (1.56 95% CI 1.06-2.33; 1.69 95% CI 1.05-2.68, respectively) and G2 (1.91 95% CI 1.05-3.24; 2.13 95% CI 1.14-3.41, respectively) vs. G0. No treatment risk reduction was observed in haematological malignancies, cardiovascular events and endocrinological comorbidities. CONCLUSIONS: Overall, our study confirms the safety of TNFi and anti-IL in SpA patients, albeit with some caveats pertaining to solid cancers, OGID and fibromyalgia. Furthermore, taking into consideration causality with observational data may yield more reliable and relevant clinical information.

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Antirreumáticos , Fibromialgia , Neoplasias , Espondiloartritis , Humanos , Antirreumáticos/uso terapéutico , Comorbilidad , Fibromialgia/epidemiología , Neoplasias/epidemiología , Espondiloartritis/diagnóstico , Espondiloartritis/tratamiento farmacológico , Espondiloartritis/epidemiología , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/uso terapéutico

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OBJECTIVE: Glucocorticoid-induced osteoporosis (GIOP) is a common cause of secondary osteoporosis. However, glucocorticoid requiring diseases pose a risk themselves for fracture. The aim of the present study was to determine the risk of fracture associated with variety of glucocorticoid requiring diseases independently from glucocorticoid use and other risk factors for osteoporosis. METHODS: We conducted a retrospective cross-sectional analysis of a nation-wide cohort (DeFRACalc79 database). We used multivariable regression analysis adjusting for several risk factors for fracture and glucocorticoid intake to estimate the independent role of glucocorticoid requiring illnesses on fracture risk. RESULTS: We found that patients with rheumatoid arthritis, connective tissue diseases, chronic obstructive pulmonary disease (COPD) and neurological diseases were at greater risk of vertebral or hip fracture (crude ORs 1.31, 1.20, 1.92 and 2.97 respectively). After adjusting for potential confounders COPD and neurological diseases remained significantly associated with an increased risk of vertebral or hip fractures (aORs 1.33, 95 % CI 1.18-1.49 and 2.43, 95 % CI 2.17-2.74). Rheumatoid arthritis, COPD, IBD and neurological diseases also significantly increased the risk of non-vertebral, non-hip fractures (aORs 1.23, 1.42, 1.52 and 1.94 respectively). CONCLUSION: Some glucocorticoid requiring diseases were independently associated with an increased risk of fractures. COPD and neurological diseases with both vertebral and non-vertebral fracture risk while RA and IBD were independently associated only with non-vertebral, non-hip fractures.

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Artritis Reumatoide , Fracturas de Cadera , Enfermedades Inflamatorias del Intestino , Osteoporosis , Fracturas Osteoporóticas , Enfermedad Pulmonar Obstructiva Crónica , Fracturas de la Columna Vertebral , Humanos , Femenino , Glucocorticoides/efectos adversos , Densidad Ósea , Estudios Retrospectivos , Estudios Transversales , Fracturas de la Columna Vertebral/epidemiología , Fracturas de la Columna Vertebral/complicaciones , Osteoporosis/complicaciones , Osteoporosis/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Factores de Riesgo , Artritis Reumatoide/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/epidemiología , Fracturas de Cadera/epidemiología , Fracturas de Cadera/complicaciones , Fracturas Osteoporóticas/inducido químicamente , Fracturas Osteoporóticas/epidemiología , Fracturas Osteoporóticas/complicaciones

RESUMEN

A growing amount of evidence suggests that gut microbiota plays an important role in human health, including a possible role in the pathogenesis of rheumatic and musculoskeletal diseases (RMD). We analysed the current evidence about the role of microbiota in rheumatoid arthritis (RA), spondyloarthritis (SpA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). In RA, we found a general consensus regarding a reduction of diversity and a specific bacterial signature, with consistent changes according to the different ethnic and geographical areas. The major pathogenetic role in RA is recognised for P. copri, L. salivarius and Collinsella, even if findings become more heterogeneous when considering established disease. In SpA, we found a relative gut abundance of Akkermansia, Coprococcus, Ruminoccocus and a relative reduction in Bacterioides and Firmicutes spp. Human and preclinical data suggest loss of mucosal barrier, increased permeability and Th1- and Th17-mediated inflammation. Additionally, HLA-B27 seems to play a role in shaping the intestinal microbiota and the consequent inflammation. In SLE, the typical gut microbiota signature was characterised by a reduction in the Firmicutes/Bacteroidetes ratio and by enrichment of Rhodococcus, Eggerthella, Klebsiella, Prevotella, Eubacterium and Flavonifractor, even if their real pathogenic impact remains unclear. In SSc, gastrointestinal dysbiosis is well documented with an increase of pro-inflammatory species (Fusobacterium, Prevotella, Ruminococcus, Akkermansia, γ-Proteobacteria, Erwinia, Trabsulsiella, Bifidobacterium, Lactobacillus, Firmicutes and Actinobacteria) and a reduction of species as Faecalibacterium, Clostridium, Bacteroidetes and Rikenella. In conclusion, seems possible to recognise a distinct gut microbiota profile for each RMD, even if significant differences in bacterial species do exist between different studies and there is a high risk of bias due to the cross-sectional nature of such studies. Therefore longitudinal studies are needed, especially on patients with preclinical and early disease, to investigate the real role of gut microbiota in the pathogenesis of RMD.

Asunto(s)

Microbioma Gastrointestinal , Enfermedades Reumáticas , Humanos , Microbioma Gastrointestinal/fisiología , Enfermedades Reumáticas/microbiología , Artritis Reumatoide/microbiología

RESUMEN

OBJECTIVES: Complex regional pain syndrome (CRPS) is a painful disease that leads to chronic pain and disability. Bisphosphonates are largely used in the real-life for the treatment of CRPS, but data on long-term effectiveness and its predictors are lacking. METHODS: We conducted a longitudinal observational study on patients with type I CRPS treated with IV neridronate (100 mg on 4 occasions). Clinical and demographic characteristics were collected at baseline, after 3 months (M3) and after 12 months (M12). Multivariable logistic regression was employed to determine the factors associated with long-term response to treatment. RESULTS: 103 patients with type I CRPS treated with IV neridronate were included in the study. Mean VAS pain at baseline was 79.1 mm and decreased significantly at M3 (-45.9 mm, 95% CI 40.1 to 51.8) and M12 (-61.6 mm, 95% CI 55.3 to 67.9). Hyperalgesia and allodynia resolved in 84.3% and 88.1% of patients at M12. Loss of motion resolved in 53.5% of patients. The predictors of excellent response were gender (male better), predisposing event to CRPS (no event being better than any predisposing event), site of CRPS (lower limb being better), and early response at M3 on VAS pain (2.5 times the chance of being excellent responder every 10 mm decrease). CONCLUSIONS: In this real-life study neridronate was associated with rapid and progressive improvement of symptoms of CRPS which was maintained up to 3 years of follow-up. The predictors of excellent response were early response, lower limb localisation, absence of predisposing events and male gender.