RESUMEN
OBJECTIVES: Mixed cryoglobulinaemic vasculitis (MCV) is an immune-complex-mediated systemic vasculitis characterised by heterogeneous clinical manifestations mainly involving lymphatic system, skin, kidney and peripheral nervous system. Although MCV patients have been included in priority programs for vaccination against SARS-CoV-2 in Italy, limited information is available for these patients. The aims of this multicentre Italian study were to investigate SARS-CoV-2 vaccination rate in MCV patients and its safety profile. METHODS: All MCV patients referring to participating centres were assessed with an interview-based survey about vaccination, reasons for not getting vaccinated, adverse events (AE), and disease flares within a month after vaccination. RESULTS: A total of 416 patients were included in the study. Among participants, 7.7% did not get vaccinated, mainly for fear related to vaccine side-effects (50%) or medical decision (18.8%). They were more frequently treated with chronic glucocorticoids or rituximab (p=0.049 and p=0.043, respectively). Mild and self-limiting AE were recorded in 31.7% of cases, while post-vaccination vasculitis flares were observed in 5.3% of subjects. Disease relapses were mainly observed in patients with peripheral neuropathy or skin vasculitis (40% and 25%, respectively). CONCLUSIONS: Vaccination against SARS-CoV-2 has been performed in a high percentage of MCV patients with encouraging safety profile. Vasculitis flares rate was in line with that observed for other autoimmune diseases, despite patients with purpura or peripheral neuropathy seem to be at risk for symptoms' exacerbation. Patients' hesitancy, rituximab and glucocorticoids treatment were the main reasons for delaying vaccination.
Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Crioglobulinemia , Arteritis de Células Gigantes , Granulomatosis con Poliangitis , Poliarteritis Nudosa , Humanos , COVID-19/complicaciones , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Glucocorticoides , Italia/epidemiología , Rituximab , SARS-CoV-2 , Vacunación/efectos adversosRESUMEN
People with cryoglobulinaemic vasculitis (CV) have an increased risk of infections, attributed to different causes: impairment of the immune system due to the disease itself, comorbidities, and immunosuppressive therapy. Therefore, these patients may be at high risk for a more severe course of COVID-19, including hospitalisation and death. Concerns about efficacy, immunogenicity and safety of vaccines, as well as doubts, not yet fully clarified in patients with systemic autoimmune diseases, represent other important factors for a low vaccination rate in people with (CV). Indeed, providing an expert position on the issues related to SARS-CoV-2 vaccination in patients suffering from CV is of critical relevance in order to help both patients and clinicians who are treating them in making the best choice in each case. A multidisciplinary task force of the Italian Group for the Study of Cryoglobulinaemia (GISC) was convened, and through a Delphi technique produced provisional recommendations regarding SARS-CoV-2 vaccination in cryoglobulinaemic patients.
Asunto(s)
COVID-19 , Crioglobulinemia , Vasculitis , Vacunas contra la COVID-19 , Humanos , Italia , SARS-CoV-2 , VacunaciónRESUMEN
Close follow-up is mandatory in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS). During the Coronavirus Disease 2019 (COVID-19) pandemic, rheumatological care was rapidly reorganized during the first peak from March 1, 2020 to May 31, 2020, and all patients with RA, PsA, and AS being treated with a subcutaneous biologic disease-modifying anti-rheumatic drug or oral targeted synthetic disease-modifying anti-rheumatic drug were followed remotely. A retrospective database analysis of these 431 patients before and after this period is presented herein. A rheumatologist directly contacted all patients by telephone. Patients could also enter data on patient-reported outcomes remotely using the digital platform iAR Plus. General health (GH) and visual analog scale (VAS) pain were the main outcomes along with FACIT and disease-specific questionnaires (RADAI, ROAD, PROCLARA for RA, and BASDAI, BASGI, BASFI for AS). In all, 449 visits were postponed (69.9% of all scheduled visits); telephone evaluation was deemed inadequate in 193 instances, and patients underwent a standard outpatient visit. Comparing patients on telemedicine to those who underwent hospital visits, we found no statistically significant differences in GH (35.3 vs 39.3; p = 0.24), VAS (33.3 vs 37.1; p = 0.29), or other specific outcome measures in patients with RA, PsA, or AS. These results show that telemedicine has undoubted benefits, and in light of the ongoing COVID-19 pandemic, it is likely that many patients with these diseases may prefer it.
Asunto(s)
Artritis/tratamiento farmacológico , COVID-19/epidemiología , Medición de Resultados Informados por el Paciente , SARS-CoV-2 , Telemedicina , Adulto , Anciano , Artritis Psoriásica/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Estudios Retrospectivos , Espondilitis Anquilosante/tratamiento farmacológicoRESUMEN
Peripheral neuropathy (PN) has been detected in up to 69% of patients with mixed cryoglobulinaemic syndrome (MCS). PN should be considered in any patient with sensory and/or motor signs and symptoms in the limbs. Electrodiagnostic tests are mandatory for the diagnosis of PN. Several different sets of diagnostic criteria have been created to assess it. All patients suspected of having neuropathy should undergo a nerve conduction study. A complete neurological evaluation at baseline and periodically should be done possibly by the same neurologists. The authors recommend rigorous scientific evidences that may help to obtain superior tools for accurate diagnosis and management of these conditions. Clinicians, armed with experience and recommendations, can find in this review data-driven guidelines to apply treatments of MCS and closely related disorders.
Asunto(s)
Crioglobulinemia , Enfermedades del Sistema Nervioso Periférico , Crioglobulinemia/complicaciones , Crioglobulinemia/diagnóstico , Crioglobulinemia/terapia , Humanos , Conducción Nerviosa , Examen Neurológico , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Enfermedades del Sistema Nervioso Periférico/etiología , Enfermedades del Sistema Nervioso Periférico/terapiaRESUMEN
BACKGROUND/AIMS: the anti-vascular endothelial growth factors (VEGF), Aflibercept and Ranibizumab, are used for the treatment of macular degeneration. Here we examined the involvement of nitric oxide (NO), mitochondria function and of apoptosis/autophagy in their antioxidant effects in human retinal pigment epithelium cells (RPE). METHODS: RPE were exposed to Ranibizumab/Aflibercept in the absence or presence of NO synthase (NOS) inhibitor and of autophagy activator/blocker, rapamicyn/3-methyladenine. Specific kits were used for cell viability, NO and reactive oxygen species detection and mitochondrial membrane potential measurement, whereas Western Blot was performed for apoptosis/ autophagy markers and other kinases detection. RESULTS: In RPE cultured in physiological conditions, Aflibercept/Ranibizumab increased NO release in a dose and time-dependent way. Opposite results were obtained in RPE pretreated with hydrogen peroxide. Moreover, both the anti-VEGF agents were able to prevent the fall of cell viability and of mitochondrial membrane potential. Those effects were reduced by the NOS inhibitor and 3-methyladenine and were potentiated by rapamycin. Finally, Aflibercept and Ranibizumab counteracted the changes of apoptosis/autophagy markers, NOS, Phosphatidylinositol-3-Kinase/Protein Kinase B and Extracellular signal-regulated kinases 1/2 caused by peroxidation. CONCLUSION: Aflibercept and Ranibizumab protect RPE against peroxidation through the modulation of NO release, apoptosis and autophagy.
Asunto(s)
Inhibidores de la Angiogénesis/farmacología , Autofagia/efectos de los fármacos , Óxido Nítrico/metabolismo , Ranibizumab/farmacología , Proteínas Recombinantes de Fusión/farmacología , Adenina/análogos & derivados , Adenina/toxicidad , Animales , Apoptosis/efectos de los fármacos , Línea Celular , Proliferación Celular/efectos de los fármacos , Peróxido de Hidrógeno/toxicidad , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa/genética , Óxido Nítrico Sintasa/metabolismo , Estrés Oxidativo/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Receptores de Factores de Crecimiento Endotelial Vascular , Epitelio Pigmentado de la Retina/citología , Epitelio Pigmentado de la Retina/efectos de los fármacos , Epitelio Pigmentado de la Retina/metabolismo , Sirolimus/toxicidad , PorcinosRESUMEN
BACKGROUND/AIMS: estrogens and phytoestrogens exert hepatoprotection through mechanisms not clearly examined yet. Here, we investigated the protective effects exerted by 17ß-estradiol and genistein against oxidative stress in hepatocytes and hepatic stellate cells (HSCs) and the involvement of specific receptors and the intracellular signalling. METHODS: Huh7.5 and LX-2, alone or in co-culture with Huh7.5, were treated with 17ß-estradiol and genistein alone or in the presence of menadione and of estrogen receptors (ERs) and G protein-coupled-estrogenic-receptors (GPER) blockers. Cell viability, mitochondrial membrane potential and oxidant/antioxidant system were measured by specific kits. Western Blot was used for the analysis of Akt and p38-mitogen-activated-protein kinases (MAPK) activation and α-smooth-muscle actin expression. RESULTS: In Huh7.5, 17ß-estradiol and genistein prevented the effects of peroxidation by modulating Akt and p38MAPK activation. Similar antioxidant and protective findings were obtained in LX-2 of co-culture experiments, only. ERs and GPER blockers were able to prevent the effects of 17ß-estradiol and genistein. CONCLUSION: In Huh7.5 and LX-2, 17ß-estradiol and genistein counteract the effects of peroxidation through the involvement of ERs and GPER and by an intracellular signalling related to Akt and p38MAPK. As concerning LX-2, paracrine factors released by Huh7.5 play a key role in protection against oxidative stress.
Asunto(s)
Antioxidantes/farmacología , Estradiol/farmacología , Genisteína/farmacología , Hepatocitos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Fitoestrógenos/farmacología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Hepatocitos/metabolismo , Humanos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
OBJECTIVES: To investigate the clinical and laboratory patterns of HCV-unrelated cryoglobulinaemic vasculitis (CV), and the factors influencing its outcome. METHODS: Prospective study of all anti-HCV and HCV-RNA negative patients with CV who have been observed since January 2004 in 17 centres participating in the Italian Group for the Study of Cryoglobulinaemias (GISC). RESULTS: 175 enrolled were followed up for 677 person-years. The associated conditions were primary Sjögren's syndrome (21.1%), SLE (10.9%), other autoimmune disorders (10.9%), lymphoproliferative diseases (6.8%), solid tumours (2.3%) and HBsAg positivity (8.6%), whereas 69 patients (39.4%) had essential CV. There were significant differences in age (p<0.001), gender (p=0.002), the presence of purpura (p=0.005), arthralgia (p=0.009), liver abnormalities (p<0.001), sicca syndrome (p<0.001), lymphadenopathy (p=0.003), splenomegaly (p=0.002), and rheumatoid factor titres (p<0.001) among these groups. Type II mixed cryoglobulins were present in 96 cases (54.9%) and were independently associated with purpura and fatigue (odds ratio [OR]4.3; 95% confidence interval [CI] 1.8-10.2; p=0.001; and OR2.8; 95%CI 1.3-6.3; p=0.012). Thirty-one patients died during follow-up, a mortality rate of 46/1000 person-years. Older age (for each additional year, adjusted hazard ratio [aHR] 1.13; 95%CI 1.06-1.20; p<0.001), male gender (aHR 3.45; 95%CI 1.27-9.40; p=0.015), type II MCG (aHR 3.31; 95%CI 0.09-1.38; p=0.047) and HBsAg positivity (aHR 7.84; 95%CI 1.20-36.04; p=0.008) were independently associated with greater mortality. CONCLUSIONS: HCV-unrelated CV is a multifaceted and often disabling disorder. The associated conditions influence its clinical severity, giving rise to significantly different clinical and laboratory profiles and outcomes.
Asunto(s)
Crioglobulinemia/epidemiología , Vasculitis Sistémica/epidemiología , Biomarcadores/sangre , Proteínas del Sistema Complemento/metabolismo , Crioglobulinemia/sangre , Crioglobulinemia/inmunología , Crioglobulinemia/mortalidad , Crioglobulinas/metabolismo , Progresión de la Enfermedad , Femenino , Humanos , Incidencia , Mediadores de Inflamación/sangre , Italia/epidemiología , Estimación de Kaplan-Meier , Modelos Logísticos , Masculino , Análisis Multivariante , Oportunidad Relativa , Prevalencia , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , Vasculitis Sistémica/sangre , Vasculitis Sistémica/inmunología , Vasculitis Sistémica/mortalidad , Factores de TiempoRESUMEN
OBJECTIVE: To evaluate the efficacy and safety in the long term of a retreatment regimen with Rituximab (RTX) alone administered at clinical relapse in cryoglobulinemic vasculitis (CV). METHODS: Thirty patients with severe HCV-related CV, previously enrolled in the multicentre Italian trial on RTX in the treatment of CV, were retrospectively evaluated after the end of the trial. All of them were managed with RTX alone at clinical relapse, if any. Disease activity at the last available follow up was defined as complete remission (absence of active disease), partial remission (response > 50% of at least one manifestation among glomerulonephritis, peripheral neuropathy or skin ulcers) or active disease. RESULTS: The mean follow up after the first RTX cycle was 72.6 (20.4) months. After the end of the trial, 21/30 (70%) patients showed an active follow up [81.7 (10.9) months)], 3/30 (10%) lost follow up and 6/30 (20%) died. 12/21 (57.1%) patients were in complete disease remission, 5/21 (23.8%) showed a partial response and 4/21 (19%) had an active disease. 17/30 (56.7%) patients needed retreatment for relapse with a mean time to retreatment of 22.3 (12.1) months. Treatment survival of this regimen was 7.6 (0.3) years. Recurrent non-severe infections occurred in 3/30, with chronic hypogammaglobulinemia in 2/3 patients. CONCLUSIONS: A long-term regimen of retreatment with RTX alone given at clinical relapse seems to be effective and safe in CV, with a low rate of infections and severe hypogammaglobulinemia.
Asunto(s)
Antirreumáticos/uso terapéutico , Crioglobulinemia/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Rituximab/uso terapéutico , Vasculitis/tratamiento farmacológico , Agammaglobulinemia/tratamiento farmacológico , Agammaglobulinemia/etiología , Crioglobulinemia/etiología , Crioglobulinemia/fisiopatología , Estudios de Seguimiento , Humanos , Italia , Recurrencia , Resultado del Tratamiento , Vasculitis/etiología , Vasculitis/fisiopatologíaRESUMEN
OBJECTIVE: The aim of this study was to validate the classification criteria for cryoglobulinaemic vasculitis (CV). METHODS: Twenty-three centres were involved. New patients with CV (group A) and controls, i.e. subjects with serum cryoglobulins but lacking CV based on the gold standard of clinical judgment (group B) and subjects without cryoglobulins but with clinical features that can be observed in the course of CV (group C), were studied. Positivity of serum cryoglobulins was necessary for CV classification. Sensitivity and specificity of the criteria were calculated by comparing group A vs group B. The group A vs group C comparison was done to demonstrate the possible diagnostic utility of the criteria. RESULTS: The study included 268 patients in group A, 182 controls in group B and 193 controls in group C (small vessel vasculitis, 51.8%). The questionnaire (at least 2/3 positive answers) showed 89.0% sensitivity and 93.4% specificity; the clinical item (at least 3/4 clinical involvement) showed 75.7% sensitivity and 89.0% specificity and the laboratory item (at least 2/3 laboratory data) showed 80.2% sensitivity and 62.4% specificity. The sensitivity and specificity of the classification criteria (at least 2/3 positive items) were 89.9% and 93.5%, respectively. The comparison of group A with group C demonstrated the clinical utility of the criteria in differentiating CV from CV mimickers. CONCLUSION: Classification criteria for CV were validated in a second, large, international study confirming good sensitivity and specificity in a complex systemic disease.
Asunto(s)
Crioglobulinemia/clasificación , Vasculitis Sistémica/clasificación , Adulto , Anciano , Estudios de Casos y Controles , Crioglobulinemia/complicaciones , Crioglobulinemia/diagnóstico , Femenino , Hepatitis C/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Encuestas y Cuestionarios , Vasculitis Sistémica/diagnóstico , Vasculitis Sistémica/etiologíaRESUMEN
OBJECTIVES: Early treatment of inflammatory arthritis (IA) leads to reduced disease activity, reduced joint damage, decreased functional impairment and increased chance of remission. However, delay often occurs from referral to rheumatology appointment. This survey evaluated whether a preliminary triage carried out by healthcare workers without formal medical training could be effective in identifying patients with or without early IA. METHODS: Patients were recruited during their first call to our centre, before their first visit. A simple questionnaire, including three questions and aimed at investigating the presence of sign and symptoms of IA was developed. The same survey was administered twice: the first time, during patient's first call to our centre (telephone survey), and the second time, during their first visit with the rheumatologist (Ambulatory visit survey). We compared the outcomes of the survey with the actual diagnosis made by the rheumatologist following standard medical examination. RESULTS: In total 484 patients were included in the study, and 34/484 (7.02%) were confirmed to have early IA. The telephone survey was able to detect the non-early IA patients in 99.5% of cases; the same result was reported for the ambulatory visit survey. The median time required to complete the questionnaire was 1 minute in both surveys. CONCLUSIONS: The adoption of a simple survey, also administered by non-medical personnel, may effectively contribute to the early detection of IA.
Asunto(s)
Artritis/diagnóstico , Artritis/inmunología , Encuestas de Atención de la Salud , Tamizaje Masivo/métodos , Encuestas y Cuestionarios , Triaje/métodos , Adulto , Anciano , Atención Ambulatoria/métodos , Diagnóstico Precoz , Femenino , Humanos , Masculino , Persona de Mediana Edad , TeléfonoRESUMEN
Objective: Hepatitis B virus (HBV) infection causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Furthermore, about 20% of the patients develop extrahepatic manifestations such as cryoglobulinemic vasculitis (CV), polyarteritis nodosa, non-rheumatoid arthritis, glomerulonephritis and non-Hodgkin lymphoma. This review analyzed literature data on clinical manifestations of HBV-related CV and the impact of antiviral therapy with analoques nucleotide. Methods: A PubMed search was performed to select eligible studies in the literature, up to July 2022. Results: Some studies have analyzed clinical manifestations in HBV-related CV and have investigated the role of antiviral therapy with nucleotides analogues (NAs). Clinical manifestations of CV vary from mild to moderate (purpura, asthenia and arthralgias) to severe (leg ulcers, peripheral neuropathy, glomerulonephritis, and non-Hodking lymphoma). NAs therapy leads to suppression of HBV-DNA; therefore, it is capable of producing clinical response in the majority of patients with mild to moderate symptoms. Conclusion: Antiviral therapy with NAs is the first choice for HBV suppression and control of mild to moderate disease. In severe vasculitis (glomerulonephritis, progressive peripheral neuropathy and leg ulcers), rituximab alone or with plasma-exchange is always indicated in combination with antiviral therapy.
RESUMEN
Seasonal influenza is a frequent cause of hospitalization and mortality among patients with systemic autoimmune diseases. Despite this evidence, vaccination coverage is generally much lower than the minimum 75% target proposed by the WHO. Therefore, an active campaign was implemented in the years 2019/2020 and 2020/2021 within the Rheumatology Department of the Niguarda Hospital (Milan, Italy) to improve the vaccination coverage in patients with inflammatory arthritis. This study aims to evaluate the vaccination coverage in the 2019/2020 and 2020/2021 (active campaigns) seasons and to compare these results with the 2018/2019 season. A monocenter observational study was conducted among adult patients with rheumatoid arthritis, spondylarthritis, or psoriatic arthropathy, who were referred to the Rheumatology Department of the Niguarda Hospital. Patients were given a questionnaire to investigate previous years' vaccination coverage and to propose an influenza vaccine for the 2020/2021 season. Compared with 2018/2019, a trend for increase in vaccination coverage was reported in 2019/2020 season (+ 10.7%, p = 0.055; 45.5% of coverage) and a statistically significant increase was reported in 2020/2021 (+ 31.2%, p < 0.001; 65.9% of coverage). The increase was also significant when comparing the 2020/2021 and 2019/2020 seasons (+ 20.5%, p < 0.001). The greatest increase in vaccination coverage was observed among under-65-year-old patients. Obtained results support the implementation of active vaccination campaigns to increase vaccination coverage among patients with systemic autoimmune diseases and highlight the importance of external factors (such as the COVID-19 pandemic) in directing the patient to adopt preventive measures to avoid infections and related complications.
Asunto(s)
Artritis Reumatoide , COVID-19 , Vacunas contra la Influenza , Gripe Humana , Adulto , Humanos , Gripe Humana/prevención & control , Estaciones del Año , Cobertura de Vacunación , Pandemias , Vacunación , Italia , Programas de InmunizaciónRESUMEN
Cryoglobulinemic vasculitis (CV) or mixed cryoglobulinemic syndrome (MCS) is a systemic small-vessel vasculitis characterized by the proliferation of B-cell clones producing pathogenic immune complexes, called cryoglobulins. It is often secondary to hepatitis C virus (HCV), autoimmune diseases, and hematological malignancies. CV usually has a mild benign clinical course, but severe organ damage and life-threatening manifestations can occur. Recently, evidence in favor of rituximab (RTX), an anti-CD 20 monoclonal antibody, is emerging in CV: nevertheless, questions upon the safety of this therapeutic approach, especially in HCV patients, are still being issued and universally accepted recommendations that can help physicians in MCS treatment are lacking. A Consensus Committee provided a prioritized list of research questions to perform a systematic literature review (SLR). A search was made in Medline, Embase, and Cochrane library, updated to August 2021. Of 1227 article abstracts evaluated, 27 studies were included in the SLR, of which one SLR, 4 RCTs, and 22 observational studies. Seventeen recommendations for the management of mixed cryoglobulinemia with rituximab from the Italian Study Group of Cryoglobulinemia (GISC) were developed to give a valuable tool to the physician approaching RTX treatment in CV.
Asunto(s)
Crioglobulinemia , Hepatitis C , Vasculitis , Humanos , Rituximab/uso terapéutico , Crioglobulinemia/tratamiento farmacológico , Crioglobulinemia/complicaciones , Consenso , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Hepacivirus , Vasculitis/tratamiento farmacológico , Vasculitis/complicacionesRESUMEN
OBJECTIVE: To evaluate the potential role of CC chemokine receptor 5 (CCR5)Δ32 polymorphism in the susceptibility to and clinical expression of Behçet's disease (BD) in a cohort of Italian patients. METHODS: One hundred and ninety-six consecutive Italian patients satisfying the ISG criteria for BD were followed up for 8 years, and 180 healthy age- and sex-matched blood donors were molecularly genotyped for the CCR5Δ32 polymorphism. A standard microlymphocytotoxicity technique was used to serotype HLA-B51. The patients were subgrouped on the basis of the presence or absence of clinical manifestations. RESULTS: The distribution of the CCR5Δ32 genotype differed between BD patients and controls (P = 0.02). The CCR5Δ32 allele was more common in BD patients than in controls [P = 0.02, odds ratio (OR) 2.28 (95% CI 1.1, 4.8)]. Carriers of the CCR5Δ32 allele (Δ32/Δ32 + CCR5/Δ32) were significantly more common in BD patients than in controls [P = 0.02, OR 2.37 (95% CI 1.1, 5.1)]. Population-attributable risk was 7.1%. In categorizing patients according to gender, the association between CCR5Δ32 polymorphism and BD was similar in females and males (ORs 2.76 and 2.0, respectively). No significant differences were found when the frequencies of clinical manifestations were compared between CC5RΔ32 allele carriers and non-carriers. CONCLUSION: CCR5Δ32 polymorphism is associated with an increased susceptibility to develop BD. Chemokines may have a role in the pathophysiology of BD.
Asunto(s)
Síndrome de Behçet/genética , Predisposición Genética a la Enfermedad/genética , Polimorfismo Genético/genética , Receptores CCR5/genética , Adulto , Síndrome de Behçet/etnología , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Antígenos HLA-B/genética , Heterocigoto , Homocigoto , Humanos , Italia/etnología , MasculinoRESUMEN
OBJECTIVES: To investigate potential associations between the PlA1/A2 polymorphism of the platelet glycoprotein receptor IIIA (GpIIIa) gene and venous thrombosis and other clinical manifestations in Italian patients with Behçet's disease (BD). METHODS: Two hundred consecutive Italian patients satisfying the International Study Group criteria for BD who were followed up for seven years and 241 healthy Italian age- and gender-matched blood donors were molecularly genotyped for the PlA1/A2 polymorphism of the platelet GpIIIa gene; 118 and 117 of the 200 BD patients were also respectively genotyped for factor V Leiden and prothrombin gene G20210A polymorphisms. A standard microlymphocytotoxicity technique was used to type serological HLA class B51. The patients were grouped on the basis of the presence or absence of clinical manifestations. The diagnoses of deep vein thrombosis (DVT) and superficial thrombophlebitis were initially made clinically, and then confirmed by means of ultrasonography or contrast venography. The distribution of the PlA1/A2 genotype was investigated, and odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: The allele and genotype frequency of the PlA1/A2 polymorphism were not significantly different in the BD patients and controls, but the PlA2 allele was significantly more frequent in the BD patients with DVT than the controls (p=0.023; Pcorr=0.046; OR 2.0, 95% CI 1.1-3.7). There were no associations between thrombotic events and the PlA1/A2 polymorphism in the BD patients carrying factor V Leiden or prothrombin gene G20210A mutations. The PlA2 allele was significantly less frequent in the BD patients with genital genital ulcers than in those without (26.9% vs. 43.2%; p=0.022; P corr 0.044; OR 0.48, CI 0.27-0.88). CONCLUSIONS: The PlA1/A2 polymorphism of the GpIIIa gene was associated with DVT in our Italian BD patients, but does not seem to increase the risk of DVT due to factor V Leiden or prothrombin gene G20210A mutations. There was a negative association between the A2 allele and genital ulcers.
Asunto(s)
Antígenos de Plaqueta Humana/genética , Síndrome de Behçet , Plaquetas/fisiología , Integrina beta3/genética , Trombosis de la Vena , Adolescente , Adulto , Síndrome de Behçet/sangre , Síndrome de Behçet/complicaciones , Síndrome de Behçet/genética , Factor V/genética , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Polimorfismo Genético , Protrombina/genética , Trombosis de la Vena/sangre , Trombosis de la Vena/complicaciones , Trombosis de la Vena/genética , Adulto JovenRESUMEN
Hepatitis B virus (HBV) chronic infection causes progressive liver damage, although about 20% of patients develop extrahepatic manifestations such as cryoglobulinemic vasculitis (CV). Clinical manifestations range from mild to moderate (purpura, asthenia, arthralgia) to severe (leg ulcers, peripheral neuropathy, glomerulonephritis, non-Hodgkin lymphoma). A comprehensive review of therapeutic options for HBV-related CV is lacking. Nucleos(t)ide analogues (NA) suppress HBV replication in 90-100% of cases and induce clinical response in most patients with mild-to-moderate CV. Plasma exchange can be performed in patients with severe CV and should be considered in severe or life-threatening cases combined with high doses of corticosteroids and antiviral treatment. A cautious use of rituximab can be considered only in association with NA treatment in refractory cases. A review of the literature and an analysis of data collected by six centers of the Italian Group for the Study of Cryoglobulinemia on 18 HBV-CV nucleotide/nucleoside analogues (NAs)-treated patients were carried out.
Asunto(s)
Crioglobulinemia/etiología , Crioglobulinemia/terapia , Virus de la Hepatitis B , Hepatitis B/complicaciones , Vasculitis/etiología , Vasculitis/terapia , Anciano , Terapia Combinada , Crioglobulinemia/diagnóstico , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Femenino , Estudios de Seguimiento , Hepatitis B/virología , Humanos , Italia , Masculino , Persona de Mediana Edad , Nucleósidos/análogos & derivados , Nucleósidos/uso terapéutico , Fenotipo , Resultado del Tratamiento , Vasculitis/diagnósticoRESUMEN
Rituximab (RTX) represents a milestone in the treatment of mixed cryoglobulinemic vasculitis (MCV). Despite usually well-tolerated, RTX may induce different types of adverse drug reactions, including exacerbation of vasculitis. Recently, RTX biosimilar CT-P10 has been approved in Europe for the treatment of rheumatoid arthritis, but no data are available about effectiveness and safety of CT-P10 in the treatment of MCV. In this multicenter open-label study, we analyzed the safety of CT-P10 in patients with MCV treated in first-line or after a shift by RTX originator. Fifty-one consecutive MCV patients (females/males 35/16, median age 68 years, median disease duration 42 months, 51% HCV positive) were included in the study between July and December 2018 and were treated with CT-P10 (group 1). Safety and effectiveness of CT-P10 were compared with a retrospective group (group 2) including 75 consecutive patients treated with RTX originator between July 2017 and July 2018. Thirty-six patients were treated with CT-P10 for the first time, while the other 15 switched from RTX originator. RTX was administrated with high or dosage schemes (375 mg/m2 four times a week apart/1000 mg twice one week apart or 250 mg/m2 twice one week apart). During a month period after the last infusion, 13/51 adverse events (AE) were observed in group 1 and 17/75 in group 2 (p not significant). Among them, 7/13 and 6/17 (in group 1 and 2, respectively) could be considered immune-mediated AE (p not significant). At univariate analysis patients with IM-AE were more frequently males (p = 0.04) and with a lower disease duration (p = 0.03), but both the parameters were not significant at logistic regression. About clinical response after 6 months by the end of the treatment, no differences were observed between patients treated with originator and CT-P10 regarding the response to the therapy. No differences were observed in safety and effectiveness between patients naïve at RTX or switching from originator. Despite the higher prevalence of immune-mediated AE among patients treated with CT-P10 than originator, we have observed no significant differences between the 2 groups. The use of a low-dosage regimen is more common in group 1 than in group 2, representing a possible bias of the study, possibly influencing the appearance of AE. Considering the cost/efficacy ratio of biosimilars, their use could be helpful to treat a large number of MCV patients with an effectiveness and safety comparable to originator. Multicenter studies including a large number of patients and the new RTX biosimilars could be useful to fully elucidate the possible risk of immune-mediated adverse events with biosimilar drugs. Considering the cost/efficacy ratio of CT-P10, its use could help to treat a large number of MCV patients with an effectiveness and safety comparable to originator.