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OBJECTIVES: Psoriatic arthritis (PsA) is an immune-inflammatory disease occurring in a subgroup of patients suffering from psoriasis. Dactylitis is recognised as a hallmark of PsA, being present in about 50% of patients. This article gives an overview of the complexity of psoriatic dactylitis, looking at clinical aspects as well as pathogenetic aspects and subsequent insights into treatment strategies. METHODS: The review focuses on the main evidence on pathogenesis, clinical features, and management of psoriatic dactylitis. RESULTS: In recent years, more studies have focused their attention on dactylitis in PsA patients, leading to a greater understanding of its pathogenesis and clinical presentation and to a growing expansion of the therapeutic armamentarium. Dactylitis is frequently associated with more severe PsA phenotype, often representing the initial feature of the disease. Its prompt recognition can be key for addressing early diagnosis and therapy of PsA, thus leading to better clinical and radiographic outcomes. CONCLUSIONS: There has been considerable progress in understanding psoriatic dactylitis, but major challenges remain. Although there has been a recent expansion in the therapeutic armamentarium for psoriatic dactylitis, there is still a paucity of evidence on a precision approach to this manifestation.
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OBJECTIVES: Conflicting results about clinical and subclinical atherosclerosis in systemic sclerosis (SSc) and the associated risk factors have been reported. Hence, we aimed to determine the prevalence of clinical and subclinical atherosclerosis in a large number of Italian SSc patients and the associated risk factors. METHODS: This study included 613 SSc patients from 11 Italian tertiary Rheumatologic Units. All patients underwent full history taking, clinical examination, and relevant laboratory and radiological investigations. Doppler ultrasonography (US) of the common carotid and upper and lower limbs was performed to measure carotid and femoral intima-media thickness (cIMT and fIMT), and carotid and peripheral atheroma plaques. Doppler US of the brachial artery was performed to measure flow-mediated dilatation (FMD). RESULTS: Patients were mostly women (91.4%) with a median age of 61 years (range, 20-100); a median disease duration of 14 years (range, 0-77) from the onset of the first non-Raynaud's phenomenon (RP); 9.3% had a history of clinical atherosclerosis (9 stable/unstable angina, 21 myocardial infarctions, 24 heart failure, 3 strokes, 8 transient ischaemic attack, 6 intermittent claudication, 10 atrial thrombo-embolism). In 37.1% of patients, subclinical atherosclerosis was detected, after excluding those with a history of clinical atherosclerosis. The prevalence of clinical and subclinical atherosclerosis was higher than that reported by the European Society of Cardiology and observational studies that enrolled Italian healthy individuals as a control group, respectively. CONCLUSIONS: A higher prevalence of clinical and subclinical atherosclerosis was detected in SSc Italian patients and correlated with traditional and SSc-related risk factors.
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Aterosclerosis , Grosor Intima-Media Carotídeo , Esclerodermia Sistémica , Humanos , Femenino , Esclerodermia Sistémica/epidemiología , Esclerodermia Sistémica/complicaciones , Masculino , Persona de Mediana Edad , Italia/epidemiología , Anciano , Adulto , Prevalencia , Aterosclerosis/epidemiología , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/etiología , Factores de Riesgo , Anciano de 80 o más Años , Adulto Joven , Ultrasonografía Doppler , Enfermedades Asintomáticas , Enfermedades de las Arterias Carótidas/epidemiología , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Placa Aterosclerótica/diagnóstico por imagen , Placa Aterosclerótica/epidemiologíaRESUMEN
PURPOSE: The clinical relevance of human leukocyte antigen (HLA) subtypes such as HLA-B51 on Behçet's disease (BD)-related uveitis and non-infectious uveitis (NIU) unrelated to BD remains largely unknown. METHODS: Data were prospectively collected from the International AIDA Network Registry for BD and for NIU. We assessed differences between groups (NIU unrelated to BD and positive for HLA-B51, BD-related uveitis positive for HLA-B51 and BD-related uveitis negative for HLA-B51) in terms of long-term ocular complications, visual acuity (VA) measured by best corrected visual acuity (BCVA), anatomical pattern, occurrence of retinal vasculitis (RV) and macular edema over time. RESULTS: Records of 213 patients (341 eyes) were analyzed. No differences in complications were observed (p = 0.465). With regard to VA, a significant difference was detected in median BCVA (p = 0.046), which was not maintained after Bonferroni correction (p = 0.060). RV was significantly more prevalent in NIU-affected patients who tested positive for HLA-B51, irrespective of the systemic diagnosis of BD (p = 0.025). No differences emerged in the occurrence of macular edema (p = 0.99). CONCLUSIONS: Patients with NIU testing positive for HLA-B51 exhibit an increased likelihood of RV throughout disease course, irrespective of a systemic diagnosis of BD. The rate of complications as well as VA are comparable between NIU cases unrelated to BD testing positive for HLA-B51 and uveitis associated with BD. Therefore, it is advisable to perform the HLA-B typing in patients with NIU or retinal vasculitis, even in the absence of typical BD features.
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We aimed to identify an expression profile of lncRNAs potentially related to treatment response in Psoriatic arthritis (PsA) patients, to be used as potential genomic biomarkers predictors of drug treatment effectiveness. In addition, we evaluated a possible association between lncRNAs genetic variants and the response to therapy using the clinical parameter of Disease Activity Index. For the expression study, we collected 48 treated PsA patients, monitoring the treatment response for 12 months. We initially used PCR Array and, then, we validated the results with qRT-PCR. We also retrospectively genotyped 163 treated PsA patients. Firstly, we observed a significant difference in the expression level between Responder and non-Responder patients, of 4 lncRNAs in the group of PsA patients treated with TNFi and of 3 lncRNAs in the group of patients treated with IL17i. Then, we confirmed a significant decrease of MEG3 expression in non-Responder patients compared to Responders, also considering separately the single groups of patients treated with TNFi and IL17i. In addition, our results seem to highlight a potential dose-dependent effect of rs941576 (MEG3) variant allele on Disease Activity Index. Our study suggests a possible role of the lncRNA MEG3 in the treatment response to biological drugs.
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Artritis Psoriásica , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , Artritis Psoriásica/tratamiento farmacológico , Artritis Psoriásica/genética , Masculino , Femenino , Persona de Mediana Edad , Adulto , Resultado del Tratamiento , Estudios Retrospectivos , Biomarcadores , Polimorfismo de Nucleótido Simple , Interleucina-17/genética , Interleucina-17/metabolismo , Productos Biológicos/uso terapéutico , Antirreumáticos/uso terapéuticoRESUMEN
Introduction: JAK-inhibitors (JAK-i) represent an effective treatment in Rheumatoid Arthritis (RA) and Psoriatic Arthritis (PsA). Oral glucocorticoids (OGC) are commonly used in combination with JAK-i to reach therapeutic target. We aimed to assess, in a real-life setting, the reduction of OGC dose during JAK-i treatment in active RA and PsA patients. Methods: We prospectively enrolled 103 patients (88 RA, 15 PsA) treated with JAK-i: 24% bio-naïve (b-naïve), 76% bDMARD-insufficient responders (bDMARD-IR) and 40% difficult to treat (D2T), defined as failure of ≥2 bDMARDs with different mechanism of action. Disease activity (DAS28 and DAPSA, VAS-pain, GH) and OGC dose was collected at baseline and after 3, 6 and 12 months (T3, T6, T12) of treatment. Results: In all the cohort and in b-naïve patients we reported a reduction of OGC dose at all time-points; bDMARD-IR patients were able to reduce OGC dose at T3 and T12; D2T ones only at T3. We reported an improvement of disease activity and withdrawal of OGC as early as three months of therapy, at all time-points, regardless of line of bDMARD treatment. Conclusion: Chronic OGC may cause detrimental bone, metabolic, cardiovascular side effects and infections; therefore JAK-i steroid-sparing effect may be beneficial for patients in long-term treatment.
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Artritis Psoriásica , Artritis Reumatoide , Inhibidores de las Cinasas Janus , Humanos , Masculino , Inhibidores de las Cinasas Janus/uso terapéutico , Inhibidores de las Cinasas Janus/efectos adversos , Femenino , Persona de Mediana Edad , Artritis Psoriásica/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Anciano , Adulto , Resultado del Tratamiento , Glucocorticoides/uso terapéutico , Glucocorticoides/efectos adversos , Estudios Prospectivos , Antirreumáticos/uso terapéutico , Antirreumáticos/efectos adversos , Administración OralRESUMEN
VEXAS syndrome is a recently described monogenic autoinflammatory disease capable of manifesting itself with a wide array of organs and tissues involvement. Orbital/ocular inflammatory manifestations are frequently described in VEXAS patients. The objective of this study is to further describe orbital/ocular conditions in VEXAS syndrome while investigating potential associations with other disease manifestations. In the present study, twenty-seven out of 59 (45.8 %) VEXAS patients showed an inflammatory orbital/ocular involvement during their clinical history. The most frequent orbital/ocular affections were represented by periorbital edema in 8 (13.6 %) cases, episcleritis in 5 (8.5 %) patients, scleritis in 5 (8.5 %) cases, uveitis in 4 (6.8 %) cases, conjunctivitis in 4 (6.8 %) cases, blepharitis in 3 (5.1 %) cases, orbital myositis in 2 (3.4 %) cases. A diagnosis of systemic immune-mediated disease was observed in 15 (55.6 %) cases, with relapsing polychondritis diagnosed in 12 patients. A significant association was observed between relapsing polychondritis and orbital/ocular involvement in VEXAS syndrome (Relative Risk: 2.37, 95 % C.I. 1.03-5.46, p = 0.048). Six deaths were observed in the whole cohort of patients after a median disease duration of 1.2 (IQR=5.35) years, 5 (83.3 %) of which showed orbital/ocular inflammatory involvement. In conclusion, this study confirms that orbital/ocular inflammatory involvement is a common finding in VEXAS patients, especially when relapsing polychondritis is diagnosed. This makes ophthalmologists a key figure in the diagnostic process of VEXAS syndrome. The high frequency of deaths observed in this study seems to suggest that patients with orbital/ocular involvement may require increased attention and more careful follow-up.
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Sistema de Registros , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Adulto Joven , Adolescente , Enfermedades Orbitales , Enfermedades Autoinflamatorias Hereditarias/diagnóstico , Oftalmopatías/epidemiología , Niño , Anciano , Escleritis/epidemiología , Escleritis/diagnóstico , Policondritis Recurrente/diagnóstico , Policondritis Recurrente/complicaciones , Policondritis Recurrente/epidemiologíaRESUMEN
OBJECTIVE: Evaluate spondyloarthritis (SpA) incidence in inflammatory bowel diseases (IBD) between patients treated with biological disease-modifying antirheumatic drugs (bDMARDs) and conventional DMARDs (cDMARDs) and define risk factors associated with SpA development. METHODS: Retrospective cohort study was conducted on patients with Crohn's disease (CD) or ulcerative colitis (UC) and divided into two cohorts: cDMARDs or bDMARDs/targeted synthetic (ts) DMARDs treated patients. Rheumatological assessment was performed in patients presenting musculoskeletal symptoms. Multivariate analysis and Kaplan-Meier curves were used to evaluate the adjusted SpA risk development. RESULTS: 507 patients were included in the study. 176 patients with CD received bDMARDs, 112 cDMARDs and 106 new SpA diagnosies were formulated. Females (OR 1.7 (95% CI 1.1 to 3), adjusted p=0.04), non-stricturing/non-penetrating phenotype (OR 2 (95% CI 1.1 to 3.4), adjusted p=0.01), psoriasis (OR 2.1 (95% CI 1 to 4.6), adjusted p=0.04) and non-infectious uveitis (OR 6.8 (95% CI 1.4 to 33.4), adjusted p=0.01) were associated with increased SpA risk development, while bDMARDs usage was protective (OR 0.4 (95% CI 0.2 to 0.8), adjusted p=0.01), statistically higher than cDMARDs throughout the entire follow-up (effect size 0.47). 98 patients with UC received b-tsDMARDs, 121 cDMARDs and 56 new SpA diagnoses were formulated. Females (OR 2.1 (95% CI 1 to 4.3), adjusted p=0.02) and psoriasis (OR 2.7 (95% CI 1 to 6.8), adjusted p=0.03) were associated with increased SpA risk development, while bDMARDs were protective for SpA development for up to 12 months of treatment compared with cDMARDs (p=0.03). CONCLUSIONS: bDMARDs treatment had an impact in reducing SpA development and clinical associated risk factors to transition from IBD to IBD-SpA emerged.
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Antirreumáticos , Enfermedades Inflamatorias del Intestino , Psoriasis , Espondiloartritis , Femenino , Humanos , Estudios Retrospectivos , Antirreumáticos/efectos adversos , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Espondiloartritis/complicaciones , Espondiloartritis/tratamiento farmacológico , Espondiloartritis/epidemiología , Psoriasis/epidemiología , Terapia Biológica/efectos adversosRESUMEN
VEXAS is a prototypic hemato-inflammatory disease combining rheumatologic and hematologic disorders in a molecularly defined nosological entity. In this nationwide study, we aimed at screenshotting the current diagnostic capabilities and clinical-genomic features of VEXAS, and tracked UBA1 longitudinal clonal dynamics upon different therapeutics, including allogeneic hematopoietic cell transplant. We leveraged a collaboration between the Italian Society of Experimental Hematology and of Rheumatology and disseminated a national survey to collect clinical and molecular patient information. Overall, 13/29 centers performed UBA1 genomic testing locally, including Sanger sequencing (46%), next-generation sequencing (23%), droplet digital polymerase chain reaction (8%), or combination (23%). A total of 41 male patients were identified, majority (51%) with threonine substitutions at Met41 hotspot, followed by valine and leucine (27% and 8%). Median age at VEXAS diagnosis was 67 years. All patients displayed anemia (median hemoglobin 9.1 g/dL), with macrocytosis. Bone marrow vacuoles were observed in most cases (89%). The most common rheumatologic association was polychondritis (49%). A concomitant myelodysplastic neoplasm/syndrome (MDS) was diagnosed in 71% of patients (n = 28), chiefly exhibiting lower Revised International Prognostic Scoring System risk profiles. Karyotype was normal in all patients, except three MDS cases showing -Y, t(12;16)(q13;q24), and +8. The most frequently mutated gene was DNMT3A (n = 10), followed by TET2 (n = 3). At last follow-up, five patients died and two patients progressed to acute leukemia. Longitudinal UBA1 clonal dynamics demonstrated mutational clearance following transplant. We collected a nationwide interdisciplinary VEXAS patient cohort, characterized by heterogeneous rheumatologic manifestations and treatments used. MDS was diagnosed in 71% of cases. Patients exhibited various longitudinal UBA1 clonal dynamics.
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Artritis Reumatoide , Trasplante de Células Madre Hematopoyéticas , Leucemia , Síndromes Mielodisplásicos , Enfermedades Cutáneas Genéticas , Humanos , Masculino , Anciano , Síndromes Mielodisplásicos/diagnóstico , Síndromes Mielodisplásicos/genética , Síndromes Mielodisplásicos/terapia , MutaciónRESUMEN
OBJECTIVE: The aim was to evaluate the sex differences in sensitivity, specificity, positive and negative predictive values, and likelihood ratio of the outcome indices minimal disease activity (MDA), Disease Activity Score for Psoriatic Arthritis (DAPSA), and Psoriatic Arthritis Impact of Disease (PsAID) with respect to clinical remission, evaluated from both the physician and patient perspective, in a multicenter cohort of patients with PsA. METHODS: In this cross-sectional analysis of 2 longitudinal cohorts, all patients with PsA consecutively attending our rheumatology units were considered potentially eligible for the study. In all patients, a complete clinical examination was carried out. The DAPSA was calculated for each patient (DAPSA values ≤ 4 were considered as remission) and MDA was also evaluated. Patient and physician global assessment values ≤ 1 were considered as a surrogate of remission from the patient and physician perspective, respectively. RESULTS: Two hundred seventy-two patients with PsA were enrolled (mean age 55.7 [SD 12.4]; 141 male, 131 female). In both sexes, MDA had good sensitivity and specificity toward remission as assessed by the rheumatologist. Remission according to DAPSA had excellent values of specificity but lacks sensitivity in both sexes. PsAID ≤ 4 had excellent values of sensitivity but lacked specificity in both sexes. Remission defined by DAPSA values was found to be more sensitive and specific in female patients (45.4% and 100%, respectively) than in male patients (33.3% and 84.2%, respectively) with respect to physician-judged remission. CONCLUSION: The results of this study demonstrate for the first time, to our knowledge, that some differences between the 2 sexes on the different outcome indices are possible. This could be important in the clinical management of patients with PsA.
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Artritis Psoriásica , Médicos , Humanos , Masculino , Femenino , Persona de Mediana Edad , Artritis Psoriásica/diagnóstico , Artritis Psoriásica/tratamiento farmacológico , Estudios Transversales , Inducción de Remisión , Índice de Severidad de la EnfermedadRESUMEN
To characterize clinical and laboratory signs of patients with Still's disease experiencing macrophage activation syndrome (MAS) and identify factors associated with MAS development. Patients with Still's disease classified according to internationally accepted criteria were enrolled in the AutoInflammatory Disease Alliance (AIDA) Still's Disease Registry. Clinical and laboratory features observed during the inflammatory attack complicated by MAS were included in univariate and multivariate logistic regression analysis to identify factors associated to MAS development. A total of 414 patients with Still's disease were included; 39 (9.4%) of them developed MAS during clinical history. At univariate analyses, the following variables were significantly associated with MAS: classification of arthritis based on the number of joints involved (p = 0.003), liver involvement (p = 0.04), hepatomegaly (p = 0.02), hepatic failure (p = 0.01), axillary lymphadenopathy (p = 0.04), pneumonia (p = 0.03), acute respiratory distress syndrome (p < 0.001), platelet abnormalities (p < 0.001), high serum ferritin levels (p = 0.009), abnormal liver function tests (p = 0.009), hypoalbuminemia (p = 0.002), increased LDH (p = 0.001), and LDH serum levels (p < 0.001). At multivariate analysis, hepatomegaly (OR 8.7, 95% CI 1.9-52.6, p = 0.007) and monoarthritis (OR 15.8, 95% CI 2.9-97.1, p = 0.001), were directly associated with MAS, while the decade of life at Still's disease onset (OR 0.6, 95% CI 0.4-0.9, p = 0.045), a normal platelet count (OR 0.1, 95% CI 0.01-0.8, p = 0.034) or thrombocytosis (OR 0.01, 95% CI 0.0-0.2, p = 0.008) resulted to be protective. Clinical and laboratory factors associated with MAS development have been identified in a large cohort of patients based on real-life data.
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Hepatopatías , Síndrome de Activación Macrofágica , Enfermedad de Still del Adulto , Humanos , Síndrome de Activación Macrofágica/diagnóstico , Síndrome de Activación Macrofágica/complicaciones , Hepatomegalia/complicaciones , Enfermedad de Still del Adulto/complicaciones , Enfermedad de Still del Adulto/diagnóstico , Hepatopatías/complicacionesRESUMEN
INTRODUCTION: The aim of this work is to characterize which Minimal Disease Activity (MDA) domains are mainly achieved, based on different treatments, in psoriatic arthritis (PsA) patients. Moreover, the association between MDA achievement and the different treatment groups was assessed. METHODS: We conducted a cross-sectional analysis of two longitudinal PsA groups. Inclusion criteria were: age ≥ 18 years, PsA diagnosis, stable treatment for at least 6 months. Patients were grouped depending on the therapy: group 1: Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)/cyclooxygenase 2 inhibitors (COX2i)/steroids, group 2: conventional synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs), group 3: Tumor Necrosis Factor α inhibitors (TNFi), group 4: interleukin inhibitors (IL)12-23i or IL-23i, group 5: IL-17i, group 6: phosphodiesterase 4 inhibitors (PD4i). For each group, the achieved domains based on therapy were assessed. Multivariate logistic regression analysis was performed to assess the association between the treatment groups and the MDA achievement. RESULTS: A total of 220 patients were enrolled, and MDA was achieved in 45.8% of them. In all treatment groups, the first MDA domains achieved were: body surface area ≤ 3, swollen joint count ≤ 1 and Leeds Enthesitis Index ≤ 1, while MDA domains less frequently achieved were Patient Global Assessment (PtgA) ≤ 2 cm and pain on visual analogue scale ≤ 1.5 cm. The logistic regression analysis showed higher odds ratios for the achievement of the MDA in those patients in groups 3 and 4. CONCLUSIONS: In each treatment group, MDA domains less frequently achieved were PtGA and pain, suggesting that "patient-driven domains" are still an unmet need. Due to the study design and the low number of patients in some groups, it is not possible to clearly define which MDA domain was achieved or not based on treatment; however, it seems that some differences could be present. If larger and prospective studies confirm our preliminary results, we could move toward a personalized/domain treatment approach in PsA.
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Introduction: This paper describes the creation and preliminary results of a patient-driven registry for the collection of patient-reported outcomes (PROs) and patient-reported experiences (PREs) in Behçet's disease (BD). Methods: The project was coordinated by the University of Siena and the Italian patient advocacy organization SIMBA (Associazione Italiana Sindrome e Malattia di Behçet), in the context of the AIDA (AutoInflammatory Diseases Alliance) Network programme. Quality of life, fatigue, socioeconomic impact of the disease and therapeutic adherence were selected as core domains to include in the registry. Results: Respondents were reached via SIMBA communication channels in 167 cases (83.5%) and the AIDA Network affiliated clinical centers in 33 cases (16.5%). The median value of the Behçet's Disease Quality of Life (BDQoL) score was 14 (IQR 11, range 0-30), indicating a medium quality of life, and the median Global Fatigue Index (GFI) was 38.7 (IQR 10.9, range 1-50), expressing a significant level of fatigue. The mean Beliefs about Medicines Questionnaire (BMQ) necessity-concern differential was 0.9 ± 1.1 (range - 1.8-4), showing that the registry participants prioritized necessity belief over concerns to a limited extent. As for the socioeconomic impact of BD, in 104 out of 187 cases (55.6%), patients had to pay from their own pocket for medical exams required to reach the diagnosis. The low family socioeconomic status (p < 0.001), the presence of any major organ involvement (p < 0.031), the presence of gastro-intestinal (p < 0.001), neurological (p = 0.012) and musculoskeletal (p = 0.022) symptoms, recurrent fever (p = 0.002), and headache (p < 0.001) were associated to a higher number of accesses to the healthcare system. Multiple linear regression showed that the BDQoL score could significantly predict the global socioeconomic impact of BD (F = 14.519, OR 1.162 [CI 0.557-1.766], p < 0.001). Discussion: Preliminary results from the AIDA for Patients BD registry were consistent with data available in the literature, confirming that PROs and PREs could be easily provided by the patient remotely to integrate physician-driven registries with complementary and reliable information.
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Non-infectious uveitis (NIU) can be an early or even the first extra-articular manifestation of systemic rheumatic diseases, or the first one; thus, rheumatologists are often involved in the diagnostic and therapeutic assessment of NIU. We evaluated 130 patients with a diagnosis of NIU who were admitted to two Italian rheumatologic clinics (Tor Vergata University Hospital in Rome, and Federico II University in Naples) from January 2018 to December 2021. Anterior uveitis (AU) occurred in 75.4% of patients, followed by posterior uveitis (PU, 21.5%); acute (54.6%) and recurrent (35.4%) NIU were more documented than chronic NIU (10%), and a bilateral involvement was observed in 38.7% of cases. Half of NIU cases were associated with spondyloarthritis (SpA); the remaining were affected by Behçet disease (BD)-related uveitis (13.9%) and idiopathic NIU (9.2%). HLA-B27+ patients (34.8%) had a higher prevalence of anterior and unilateral NIU (p = 0.005) with acute course (p = 0.04) than HLA-B27- patients. On the contrary, HLA-B51+ patients (19.6%) had mostly PU and bilateral NIU (p < 0.0001) and recurrent course (p = 0.04) than HLA-B51- patients. At the first rheumatologic referral, 117 patients (90%) received systemic treatments. Findings from this study demonstrate that rheumatologic referral has a pivotal role in the diagnostic work-up of NIU and may dramatically influence NIU-treatment strategies.
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Artritis Reumatoide , Uveítis , Humanos , Antígeno HLA-B27/uso terapéutico , Reumatólogos , Antígeno HLA-B51 , Uveítis/diagnóstico , Uveítis/epidemiología , Uveítis/etiología , Derivación y Consulta , Italia/epidemiologíaRESUMEN
Complement system (CS) dysregulation is a key factor in the pathogenesis of different autoimmune diseases playing a central role in many immune innate and adaptive processes. Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by ta breach of self-tolerance leading to a synovitis and extra-articular manifestations. The CS is activated in RA and seems not only to mediate direct tissue damage but also play a role in the initiation of RA pathogenetic mechanisms through interactions with citrullinated proteins. Interstitial lung disease (ILD) represents the most common extra-articular manifestation that can lead to progressive fibrosis. In this review, we focused on the evidence of CS dysregulation in RA and in ILD, and highlighted the role of the CS in both the innate and adaptive immune responses in the development of diseases, by using idiopathic pulmonary fibrosis as a model of lung disease. As a proof of concept, we dissected the evidence that several treatments used to treat RA and ILD such as glucocorticoids, pirfenidone, disease modifying antirheumatic drugs, targeted biologics such as tumor necrosis factor (TNF)-inhibitors, rituximab, tocilizumab, and nintedanib may act indirectly on the CS, suggesting that the CS might represent a potential therapeutic target in these complex diseases.
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Introduction: Hereditary angioedema due to C1-inhibitor deficiency is influenced by hormonal factors, with a more severe course of disease in women. Our study aims to deepen the impact of puberty on onset, frequency, location and severity of attacks. Methods: Retrospective data were collected through a semi-structured questionnaire and shared by 10 Italian reference centers of the Italian Network for Hereditary and Acquired Angioedema (ITACA). Results: The proportion of symptomatic patients increased significantly after puberty (98.2% vs 83.9%, p=0.002 in males; 96.3% vs 68,4%, p<0.001 in females); the monthly mean of acute attacks was significantly higher after puberty, and this occurred both in females (median (IQR) = 0.41(2) in the three years before puberty vs 2(2.17) in the three years after, p<0.001) and in males (1(1.92) vs 1.25(1.56) respectively, p<0.001). The increase was greater in females. No significant differences were detected in attack location before and after puberty. Discussion: Overall, our study confirms previous reports on a more severe phenotype in the female gender. Puberty predisposes to increased numbers of angioedema attacks, in particular in female patients.
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INTRODUCTION: Psoriatic arthritis (PsA) is a chronic inflammatory disease affecting about one-third of subjects with psoriasis. Several treatment modalities targeting Janus Kinase pathways and intracellular inflammatory cascade are now available and under clinical investigation to treat this disease. AREAS COVERED: This review describes ongoing and recently completed phase 2 and 3 randomized clinical trials (RCTs) evaluating the efficacy and safety of approved JAK (Tofacitinib and Upadacitinib) and investigational JAK inhibitors (JAK1 inhibitors: Filgotinib and Ivarmacitinib (SHR0302); TYK2 inhibitors: Brepocitinib (PF-06700841) Deucravacitinib (BMS-986165), and NDI-034858) in PsA through February 2023. EXPERT OPINION: Current standard of care has significantly improved the quality of life in PsA. Recently approved JAK inhibitors for PsA have addressed many of the unmet needs of PsA, particularly of those with severe phenotypes. Preliminary results from several RCTs have reported good and fast efficacy and an acceptable safety profile of investigational JAK inhibitors in PsA. Additional clinical trials and long-term outcome data on these agents are necessary for increasing available therapeutic options for PsA.
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Antirreumáticos , Artritis Psoriásica , Inhibidores de las Cinasas Janus , Psoriasis , Humanos , Artritis Psoriásica/tratamiento farmacológico , Inhibidores de las Cinasas Janus/uso terapéutico , Psoriasis/tratamiento farmacológico , Quinasas Janus , Antirreumáticos/uso terapéuticoRESUMEN
Recent studies have shown that people who are immunocompromised may inadvertently play a role in spurring the mutations of the virus that create new variants. This is because some immunocompromised individuals remain at risk of getting COVID-19 despite vaccination, experience more severe disease, are susceptible to being chronically infected and remain contagious for longer if they become infected and considering that immunocompromised individuals represent approximately 2% of the overall population, this aspect should be carefully considered. So far, some autoimmune rheumatic disease (ARD) patients with COVID-19 have been treated with antiviral therapies or anti-SARS-CoV-2 antibody products. However, there is no homogeneous approach to these treatment strategies. This issue was addressed within the European Reference Network (ERN) on Rare and Complex Connective Tissue and Musculoskeletal Diseases (ReCONNET) in a discussion among experts and patient's representatives in the context of the rare and complex connective tissue diseases (rCTDs) covered by the Network. ERN ReCONNET is one of the 24 ERNs launched by the European Commission in 2017 with the aim of tackling low prevalence and rare diseases that require highly specialised treatment and promoting concentration of knowledge and resources through virtual networks involving healthcare providers (HCPs) across the European Union (EU). Considering the urgent need to provide guidance not only to the rCTDs community, but also to the whole ARDs community, a multidisciplinary Task Force, including expert clinicians and European Patient Advocacy Group (ePAG) Advocates, was created in the framework of ERN ReCONNET with the aim of developing overarching principles (OP) and points-to-consider (PtC) on a homogenous approach to treat immunocompromised patients with ARDs (with a particular focus on CTDs) affected by COVID-19 using antiviral therapies and anti-SARS-CoV-2 antibody products. The present work reports the final OP and PtC agreed by the Task Force.
Asunto(s)
Enfermedades Autoinmunes , COVID-19 , Síndrome de Dificultad Respiratoria , Enfermedades Reumáticas , Humanos , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Reumáticas/epidemiología , Antivirales/uso terapéuticoRESUMEN
BACKGROUND: Rheumatoid Arthritis (RA) is a chronic inflammatory disease with a heterogeneous treatments' clinical response. Goals of treatment are remission and low disease activity, which are not achieved in all patients despite the introduction of early treatment and the treat to target strategy. OBJECTIVE: To investigate the causes of disease-modifying antirheumatic drugs (DMARDs) discontinuation and treatment failure and multiple failure for inefficacy, and to identify possible failure predictors' according to RA patient characteristics in a real-world setting. METHODS: 718 RA patients were retrospectively evaluated. Conventional synthetic (cs) and biologic (b)DMARDs treatments line/s, effectiveness, and reasons of discontinuations were evaluated. Patients failing to at least two csDMARDs or bDMARDs' drug for inefficacy were defined "csDMARDs multifailure" and "bDMARDs multifailure", respectively. Discontinuation of at least two cs- and bDMARDs was termed "global multifailure". RESULTS: In total, 1422 csDMARDs and 714 bDMARDs treatment were analysed. Causes of csDMARDs discontinuation were intolerance (21.8%), inefficacy (20.2%), acute adverse reactions (5.3%) and severe infections (0.6%) while csDMARDs multifailure for inefficacy was observed in 5.7% of cases. Reasons of bDMARDs withdrawal were inefficacy (29%), intolerance (10.0%), acute adverse reaction (6.3%) and severe infections (1.5%). Altogether, 8.4% of patients were bDMARDs multifailure for inefficacy while 16.6% were global multifailure. Longstanding disease (≥ 12 months) and smoke habit, resulted as positive predictor of csDMARDs failure (OR 2.6 and OR 2.7, respectively). Thyreopathy was associated with both csDMARDs failure and global multifailure (OR 2.4 and OR 1.8, respectively). Higher prevalence of failure to at least one bDMARDs and global multifailure was detected in female than male (OR 2.3 and OR 2, respectively). CONCLUSIONS: Different causes of drug discontinuation were observed on DMARDs treatments. Demographic and clinical features were identified as possible predictors of both cs- and bDMARDs treatment failure and multiple failure, underlining the need of a more personalized therapeutic approach to achieve treatment targets.