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The development of intravenous IgG (IVIG) formulations in the 1970s enabled expanded use for treating primary antibody deficiency syndromes and autoimmune conditions. Recent advancements include the use of IVIG in secondary immune deficiencies related to hematologic malignancies and stem cell transplantation, along with the newly emerging prophylactic applications following chimeric antigen receptor T-cell (CAR-T) therapies. Novel therapeutic areas such as bispecific antibodies (BsAbs) for lymphoma and myeloma have increased the use of IgG, given the associated risks of infections. Today, the concept of a rational personalized clinical use of IgG in the context of evolving clinical indications in high-income countries (HIC) is emerging, as unmet challenges in line with managing shortages due to increasing demands globally. The current work aims to review and link the indications for IgG to their characteristics and formulations, their dose, route and frequency of administrations and duration of therapy to meet the needs of individual patients. It will also explore the means to rationalize and monitor IgG use in HIC in the time of shortage, while explaining pragmatic strategies to improve supply and use in low- and middle-income countries (LMIC).
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PURPOSE OF REVIEW: The main purpose of this review is to present newly reported cutaneous manifestations of systemic vasculitis, updates in investigations to verify systemic involvement in cases with cutaneous vasculitis and new therapeutic guidelines. The spectrum of COVID-19-related vasculitis is also covered. RECENT FINDINGS: Only a few reports highlighted new cutaneous presentations or associations with some systemic vasculitic entities. For example, the association of inflammatory disorders with Takayasu arteritis, the importance of considering Kawasaki disease in febrile children with erythema nodosum, the development of necrotic ulcers on fingers and toes in Behçet's disease and the possible presence of polyarteritis nodosa-like pathological features in vulvar ulcers of Behçet's disease. New attempts to classify cutaneous manifestations of giant cell arteritis (GCA) and antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and the diagnostic investigations for cutaneous vasculitis cases to verify systemic involvement are discussed. Treatment of systemic vasculitis with cutaneous vasculitis should be tailored according to disease status. A plethora of reports in the past 2 years focused on the broad spectrum of COVID-19 vasculitic manifestations. SUMMARY: Although newly reported cutaneous manifestations of systemic vasculitis are relatively uncommon, the plethora of reports in the past 2 years on COVID-19 vasculitis necessitates the expansion of the classification of vasculitis associated with probable cause to include severe acute respiratory syndrome coronavirus-2 (SARS-Cov-2) vasculitis.
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Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , COVID-19 , Enfermedades Cutáneas Vasculares , Arteritis de Takayasu , Humanos , SARS-CoV-2 , Arteritis de Takayasu/complicaciones , Arteritis de Takayasu/diagnósticoRESUMEN
INTRODUCTION: Direct-acting antiviral agents (DAAs) have modified the management of chronic hepatitis C virus (HCV) infection, including HCV-related cryoglobulinemic vasculitis (CryoVas). However, patients might experience vasculitis relapse, and no reliable predictors of CryoVas relapse after sustained virologic response (SVR) have been established. We aimed to describe HCV-CryoVas relapse rates and factors associated with it. METHODS: An international multicenter cohort where patients with HCV-CryoVas from Egypt, France, and Italy treated with DAA were analyzed retrospectively. Factors associated with relapse-free survival were evaluated in a multivariate-adjusted model. RESULTS: Of 913 patients, 911 (99.8%) obtained SVR. After 35 months of the median follow-up, 798 patients (87.4%) had sustained remission of vasculitis, while 115 (12.6%) experienced CryoVas relapse. By the time of relapse, skin involvement was present in 100%, renal involvement in 85.2%, and peripheral neuropathy in 81.7%. Relapses were treated with glucocorticoids in 90.9%, associated with plasma exchange, cyclophosphamide, or rituximab in 50%, 37.3%, and 6.4%, respectively. The cumulative incidence of CryoVas relapse was 0.7% (95% CI 0.3-1.4), 12.3% (95% CI 10.2-14.6), and 13.1% (95% CI 11.0-15.5) at 12, 24, and 36 months after DAA treatment, respectively. Independent baseline risk factors associated with CryoVas relapse were male sex, skin ulcers, kidney involvement at baseline, and peripheral neuropathy at the end of DAA treatment. Death occurred in 11 relapsers, mainly due to infections. DISCUSSION: A substantial proportion of patients with CryoVas experience relapse after DAA-induced SVR. Relapses are moderate-to-severe and affect survival after 24 months, mainly due to infections. Independent risk factors for relapse or death were found.
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Crioglobulinemia , Hepatitis C Crónica , Hepatitis C , Vasculitis , Antivirales/uso terapéutico , Crioglobulinemia/complicaciones , Crioglobulinemia/etiología , Hepacivirus , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Interferones/uso terapéutico , Masculino , Recurrencia , Estudios Retrospectivos , Respuesta Virológica Sostenida , Vasculitis/tratamiento farmacológicoRESUMEN
Autoimmune rheumatic disorders (ARD) represent a wide spectrum of disorders that affect in priority the joints, bones, muscles, and connective tissues. Examples of ARD include rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrome, polymyositis, systemic sclerosis, antiphospholipid syndrome and mixed connective tissue disease. Patients with ARD often require transfusion of red cell concentrates (RCC) or other blood-derived components. The presence of an autoimmune background, often complicated by the use of immunosuppressive medications, renders these patients quite vulnerable. Exposing them to RCC, when indicated, can trigger transfusion-related immunomodulation that can be aggravated by the role played by the donor microbiome, and the complement activation and the immune dysregulation induced by iron, leading to an amplification of the immune problems. Furthermore, patients are challenged by the transfused extracellular vesicles which could have a potentially negative role, particularly in patients with antiphospholipid syndrome. Despite the very vigorous screening, transfusion transmissible infections can still represent a risk to these patients, particularly in cytomegalovirus seronegative patients or when dormant pathogens are activated in the immunosuppressed transfusion recipient. The ARD population is also more at risk for transfusion-related reactions. One, therefore, has to consider a restrictive transfusion strategy if possible and, if needed, resort to the numerous blood bank procedures to reduce the immunogenicity of blood products or use safer, more targeted, industrial plasma-derived products subjected to purification and pathogen reduction technologies.
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Síndrome Antifosfolípido , Artritis Reumatoide , Enfermedades Autoinmunes , Carcinoma de Células Renales , Neoplasias Renales , Humanos , Enfermedades Autoinmunes/tratamiento farmacológico , Transfusión Sanguínea/métodosRESUMEN
The COVID-19 pandemic caused by the SARS-CoV-2 virus has significantly disrupted and burdened the diagnostic workup and delivery of care, including transfusion, to cancer patients across the globe. Furthermore, cancer patients suffering from solid tumors or hematologic malignancies were more prone to the infection and had higher morbidity and mortality than the rest of the population. Major signaling pathways have been identified at the intersection of SARS-CoV-2 and cancer cells, often leading to tumor progression or alteration of the tumor response to therapy. The reactivation of oncogenic viruses has also been alluded to in the context and following COVID-19. Paradoxically, certain tumors responded better following the profound infection-induced immune modulation. Unveiling the mechanisms of the virus-tumor cell interactions will lead to a better understanding of the pathophysiology of both cancer progression and virus propagation. It would be challenging to monitor, through the different cancer registries, retrospectively, the response of patients who have been previously exposed to the virus in contrast to those who have not contracted the infection.
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COVID-19 , Neoplasias , Humanos , Neoplasias/terapia , Pandemias , Estudios Retrospectivos , SARS-CoV-2RESUMEN
Platelets are at the crossroads between thrombosis and inflammation. When activated, platelets can shed bioactive extracellular vesicles [pEVs] that share the hemostatic potential of their parent cells and act as bioactive shuttles of their granular contents. In a viral infection, platelets are activated, and pEVs are generated with occasional virion integration. Both platelets and pEVs are engaged in a bidirectional interaction with neutrophils and other cells of the immune system and the hemostatic pathways. Severe COVID-19 infection is characterized by a stormy thromboinflammatory response with platelets and their EVs at the center stage of this reaction. This review sheds light on the interactions of platelets, pEVS and SARS-CoV-2 infection and prognostic and potential therapeutic role of pEVs. The review also describes the role of pEVs in the rare adenovirus-based COVID-19 vaccine-induced thrombosis thrombocytopenia.
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COVID-19 , Vesículas Extracelulares , Hemostáticos , Trombosis , Plaquetas/metabolismo , Vacunas contra la COVID-19 , Vesículas Extracelulares/metabolismo , Hemostáticos/metabolismo , Humanos , SARS-CoV-2RESUMEN
OBJECTIVES: To investigate survival of IL-1 inhibitors in monogenic autoinflammatory disorders (mAID) through drug retention rate (DRR) and identify potential predictive factors of drug survival from a real-life perspective. PATIENTS AND METHODS: Multicentre retrospective study analysing patients affected by the most common mAID treated with anakinra or canakinumab. Survival curves were analysed with the Kaplan-Meier method. Statistical analysis included a Cox-proportional hazard model to detect factors responsible for drug discontinuation. RESULTS: Seventy-eight patients for a total of 102 treatment regimens were enrolled. The mean treatment duration was 29.59 months. The estimated DRR of IL-1 inhibitors at 12, 24 and 48 months of follow-up was 75.8%, 69.7% and 51.1%, respectively. Patients experiencing an adverse event had a significantly lower DRR (P=0.019). In contrast, no significant differences were observed between biologic-naïve patients and those previously treated with biologic drugs (P=0.985). Patients carrying high-penetrance mutations exhibited a significantly higher DRR compared with those with low-penetrance variants (P=0.015). Adverse events were the only variable associated with a higher hazard of treatment withdrawal [hazard ratio (HR) 2.573 (CI: 1.223, 5.411), P=0.013] on regression analysis. A significant glucorticoid-sparing effect was observed (P<0.0001). CONCLUSIONS: IL-1 inhibitors display an excellent long-term effectiveness in terms of DRR, and their survival is not influenced by the biologic line of treatment. They display a favourable safety profile, which deserves, however, a close monitoring given its impact on treatment continuation. Special attention should be paid to molecular diagnosis and mutation penetrance, as patients carrying low-penetrance variants are more likely to interrupt treatment.
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Anticuerpos Monoclonales Humanizados/farmacología , Enfermedades Autoinflamatorias Hereditarias/tratamiento farmacológico , Proteína Antagonista del Receptor de Interleucina 1/farmacología , Sistema de Registros , Adulto , Antirreumáticos/farmacología , Femenino , Estudios de Seguimiento , Humanos , Interleucina-1beta , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: To study the safety of extended monthly intravitreal infliximab injections in patients with active posterior uveitis in Behcet's disease. METHODS: This is a prospective, interventional, noncomparative, open-label, pilot study of 9 monthly intravitreal infliximab injections (1 mg/0.05 mL) for 22 eyes of 16 patients with active posterior uveitis in Behcet's disease. Control of inflammation and visual outcomes were assessed, and ocular complications were monitored during the study period. RESULTS: Successful treatment was achieved in 7 eyes (35%), and failure was encountered in 13 eyes (65%). Only seven eyes of six patients (35%) had completed the study and achieved complete resolution of inflammation with improved best-corrected visual acuity and no complications. Failure was either because of inability to control the inflammation in nine eyes (45%) or development of exacerbation of inflammation in four eyes (20%). Four eyes developed severe immunological reaction from the drug after first (n = 1), second (n = 2), and third (n = 1) injections and had to discontinue the injections. Kaplan-Meier survival analysis showed that the mean estimated time to failure was 3.3 ± 0.2 months, and all failed eyes required revision of their systemic immunotherapy to control the ocular inflammation. CONCLUSION: Intravitreal infliximab for active posterior uveitis in Behcet's disease was associated with a high complication rate and failure to control inflammation in most eyes. It should not be considered a substitute to systemic therapy.
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Síndrome de Behçet/tratamiento farmacológico , Infliximab/administración & dosificación , Uveítis Posterior/etiología , Agudeza Visual , Adulto , Síndrome de Behçet/complicaciones , Síndrome de Behçet/diagnóstico , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Intravítreas , Masculino , Proyectos Piloto , Estudios Prospectivos , Factores de Tiempo , Resultado del Tratamiento , Inhibidores del Factor de Necrosis Tumoral/administración & dosificación , Uveítis Posterior/diagnóstico , Uveítis Posterior/tratamiento farmacológico , Adulto JovenRESUMEN
Avascular necrosis (AVN) is a devastating condition that is rarely reported in patients with immune thrombocytopenia (ITP). Treatment with steroids remains a major risk factor for developing AVN. However, the incidence of AVN in patients with ITP requiring corticosteroid therapy is much less than that observed with other clinical conditions requiring corticosteroids. ITP is a bleeding disorder but can be also be a pro-thrombotic state via different mechanisms and thus could result in AVN. Among the possible causes of this pro-thrombotic state is the presence of antiphospholipid antibodies (aPLs). In this case, we report a patient with refractory ITP who developed multifocal AVN around the time she acquired new aPLs. We also discuss different mechanisms by which risk of thrombosis is increased in ITP and the relationship between ITP, aPLs and antiphospholipid syndrome.
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Anticuerpos Antifosfolípidos/inmunología , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/inmunología , Púrpura Trombocitopénica Idiopática/complicaciones , Púrpura Trombocitopénica Idiopática/inmunología , Enfermedades Vasculares/complicaciones , Enfermedades Vasculares/patología , Adulto , Anticuerpos Antifosfolípidos/sangre , Síndrome Antifosfolípido/sangre , Síndrome Antifosfolípido/diagnóstico , Biomarcadores , Femenino , Humanos , Imagen por Resonancia Magnética , Necrosis , Osteonecrosis , Recuento de Plaquetas , Púrpura Trombocitopénica Idiopática/sangre , Púrpura Trombocitopénica Idiopática/diagnósticoRESUMEN
Our microbiota is determined by many variables including ABO blood groups. The microbiota is not only confined to the gut and skin but is also recoverable from blood of healthy donors. The microbiota shape our immune system through cross reactivity with antigens, the expression of direct molecular patterns, the release of cytokines, the effects on nutrients and micronutrients and even through an interplay with epigenetics. It is likely, therefore, that a donor's microbiota could alter the antigenicity of blood and its components and potentially contribute to transfusion-related immune modulation [TRIM]. It could also potentially transmit infections. The recipient's microbiome contributes, on the other hand, to the tolerance to transfused blood, or to the development of transfusion reactions. Cancer patients are a particularly vulnerable population, often immunosuppressed with a significantly altered microbiota. They are more at risk for transmission of "dormant" bacteria via blood transfusion. Furthermore, chemotherapy and radiation induce mucositis that likely results in significant translocation of gut microbiota and abnormal immune reactions to transfused blood. It is therefore relevant to revisit transfusion thresholds and consider transfusion-saving strategies in cancer patients.
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Transfusión Sanguínea/métodos , Microbiota/inmunología , Neoplasias/terapia , HumanosRESUMEN
PURPOSE: To assess the safety and efficacy of intravitreal infliximab (1 mg/0.05 mL) in patients with refractory posterior uveitis in Behcet's disease. METHODS: Twenty patients were included in this study. Best corrected visual acuity (BCVA), vitreous haze (graded 0-4), vasculitis, retinitis, and papillopathy (presence or absence) were assessed at baseline, Day 1 and Week 2, 4, 6, 8, 12, and 18. Optical coherence tomography (OCT) central foveal thickness, fluorescein angiography, and flash electroretinogram were done at baseline and 4, 12, and 18 weeks. RESULTS: Mean baseline logMAR BCVA was 0.94 (20/160), had improved significantly by Week 2 to 0.6 (20/80) (P < 0.0001), and reached 0.36 (20/40) by Weeks 18 with three injections (P < 0.0001). Mean central foveal thickness OCT decreased significantly from baseline 361 µm to 180 µm at the end of follow-up (P < 0.0001). Profound decrease in mean vitreous haze gradings from two to 0.2 by the end follow-up (P < 0.05). There was a significant reduction in the number of patients with vasculitis (15 at baseline to 1 weeks at 18 weeks), retinitis (nine at baseline to none at 4 weeks), and papillitis (two at baseline to none at 4 weeks) (P < 0.05). No significant electrophysiological changes or ocular adverse inflammatory reactions were observed during the study period. CONCLUSION: Intravitreal infliximab appeared to be safe and effective in treating uveitis in Behcet's disease and should be considered as an alternative to systemic therapies.
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Anticuerpos Monoclonales/uso terapéutico , Síndrome de Behçet/complicaciones , Infliximab/uso terapéutico , Uveítis/tratamiento farmacológico , Adulto , Femenino , Angiografía con Fluoresceína , Estudios de Seguimiento , Humanos , Inyecciones Intravítreas , Masculino , Tomografía de Coherencia Óptica , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Agudeza VisualRESUMEN
Rheumatologic manifestations not only are encountered in leprosy but also can be the first and even the sole presenting manifestation. The hallmark of leprosy is skin and peripheral nerve affection; however, it can affect a wide range of other organs, with the joints being the commonest. We have searched PubMed with the key words leprosy, arthritis, vasculitis, rheumatic diseases, and autoantibodies in a proper combination. Relevant studies were retrieved from scanning of their abstracts. The relevant references provided in these articles were also selected and reviewed. We summarize the clinical and laboratory manifestations that make leprosy masquerade as a systemic rheumatic disease. Moreover, we report 4 Egyptian patients who presented with rheumatologic manifestations, namely, arthritis and vasculitis that turned out to be leprosy related.
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Autoinmunidad/inmunología , Lepra , Enfermedades Reumáticas , Diagnóstico Diferencial , Humanos , Lepra/diagnóstico , Lepra/inmunología , Enfermedades Reumáticas/diagnóstico , Enfermedades Reumáticas/inmunologíaRESUMEN
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.
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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
The treatment of HCV and its sequelae are used to be predominantly based on Interferon (IFN). However, this was associated with significant adverse events as a result of its immunostimulant capabilities. Since their introduction, the directly acting antiviral drugs (DAAs), have become the standard of care to treat of HCV and its complications including mixed cryoglobulinemic vasculitis (MCV). In spite of achieving sustained viral response (SVR), there appeared many reports describing unwelcome complications such as hepatocellular and hematological malignancies as well as relapses. Prolonged inflammation induced by a multitude of factors, can lead to DNA damage and affects BAFF and APRIL, which serve as markers of B-cell proliferation. We compared, head-to-head, three antiviral protocols for HCV-MCV treatment As regards the treatment response and relapse, levels of BAFF and APRIL among pegylated interferon α-based and free regimens (Sofosbuvir + Ribavirin; SOF-RIBA, Sofosbuvir + Daclatasvir; SOF-DACLA). Regarding clinical response HCV-MCV and SVR; no significant differences could be identified among the 3 different treatment protocols, and this was also independent form using IFN. We found no significant differences between IFN-based and free regimens DNA damage, markers of DNA repair, or levels of BAFF and APRIL. However, individualized drug-to-drug comparisons showed many differences. Those who were treated with IFN-based protocol showed decreased levels of DNA damage, while the other two IFN-free groups showed increased DNA damage, being the worst in SOF-DACLA group. There were increased levels of BAFF through follow-up periods in the 3 protocols being the best in SOF-DACLA group (decreased at 24 weeks). In SOF-RIBA, CGs relapsed significantly during the follow-up period. None of our patients who were treated with IFN-based protocol had significant clinico-laboratory relapse. Those who received IFN-free DAAs showed a statistically significant relapse of constitutional manifestations. Our findings suggest that IFN-based protocols are effective in treating HCV-MCV similar to IFN-free protocols. They showed lower levels of DNA damage and repair. We believe that our findings may offer an explanation for the process of lymphoproliferation, occurrence of malignancies, and relapses by shedding light on such possible mechanisms.
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Antivirales , Crioglobulinemia , Vasculitis , Humanos , Crioglobulinemia/tratamiento farmacológico , Crioglobulinemia/etiología , Antivirales/uso terapéutico , Masculino , Vasculitis/tratamiento farmacológico , Vasculitis/virología , Persona de Mediana Edad , Femenino , Anciano , Hepacivirus/efectos de los fármacos , Ribavirina/uso terapéutico , Sofosbuvir/uso terapéutico , Imidazoles/uso terapéutico , Valina/análogos & derivados , Valina/uso terapéutico , Pirrolidinas/uso terapéutico , Factor Activador de Células B , Interferón-alfa/uso terapéutico , Quimioterapia Combinada , Hepatitis C/tratamiento farmacológico , Hepatitis C/complicaciones , Hepatitis C/virología , Resultado del Tratamiento , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/virología , CarbamatosRESUMEN
INTRODUCTION: This study aims to characterize ocular manifestations of juvenile Behçet's disease (jBD). METHODS: This was a registry-based observational prospective study. All subjects with jBD from the Autoinflammatory Diseases Alliance (AIDA) Network BD Registry showing ocular manifestations before 18 years were enrolled. RESULTS: We included 27 of 1000 subjects enrolled in the registry (66.7% male patients, 45 affected eyes). The median (interquartile range [IQR]) age at ocular involvement was 14.2 (4.7) years. Uveitis affected 91.1% of eyes (anterior 11.1%, posterior 40.0%, panuveitis 40.0%), retinal vasculitis 37.8% and other manifestations 19.8%. Later onset (p = 0.01) and male predominance (p = 0.04) characterized posterior involvement. Ocular complications occurred in 51.1% of eyes. Patients with complications had earlier onset (p < 0.01), more relapses (p = 0.02) and more prolonged steroidal treatment (p = 0.02). The mean (standard deviation [SD]) central macular thickness (CMT) at the enrolment and last visit was 302.2 (58.4) and 293.3 (78.2) µm, respectively. Fluorescein angiography was pathological in 63.2% of procedures, with a mean (SD) Angiography Scoring for Uveitis Working Group (ASUWOG) of 17.9 (15.5). At the last visit, ocular damage according to the BD Overall Damage Index (BODI) was documented in 73.3% of eyes. The final mean (SD) best corrected visual acuity (BCVA) logMAR was 0.17 (0.47) and blindness (BCVA logMAR < 1.00 or central visual field ≤ 10°) occurred in 15.6% of eyes. At multivariate regression analysis, human leukocyte antigen (HLA)-B51 + independently predicted a + 0.35 change in the final BCVA logMAR (p = 0.01), while a higher BCVA logMAR at the first assessment (odds ratio [OR] 5.80; p = 0.02) independently predicted blindness. CONCLUSIONS: The results of this study may be leveraged to guide clinical practice and future research on this rare sight-threatening condition.
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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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OBJECTIVE: We aimed to evaluate the clinical usefulness of the systemic score in the prediction of life-threatening evolution in Still disease. We also aimed to assess the clinical relevance of each component of the systemic score in predicting life-threatening evolution and to derive patient subsets accordingly. METHODS: A multicenter, observational, prospective study was designed including patients included in the Gruppo Italiano Di Ricerca in Reumatologia Clinica e Sperimentale Adult-Onset Still Disease Study Group and the Autoinflammatory Disease Alliance Network Still Disease Registry. Patients were assessed to see if the variables to derive the systemic score were available. The life-threatening evolution was defined as mortality, whatever the clinical course, and/or macrophage activation syndrome, a secondary hemophagocytic lymphohistiocytosis associated with a poor prognosis. RESULTS: A total of 597 patients with Still disease were assessed (mean ± SD age 36.6 ± 17.3 years; male 44.4%). The systemic score, assessed as a continuous variable, significantly predicted the life-threatening evolution (odds ratio [OR] 1.24; 95% confidence interval [CI] 1.07-1.42; P = 0.004). A systemic score ≥7 also significantly predicted the likelihood of a patient experiencing life-threatening evolution (OR 3.36; 95% CI 1.81-6.25; P < 0.001). Assessing the clinical relevance of each component of the systemic score, liver involvement (OR 1.68; 95% CI 1.48-2.67; P = 0.031) and lung disease (OR 2.12; 95% CI 1.14-4.49; P = 0.042) both significantly predicted life-threatening evolution. The clinical characteristics of patients with liver involvement and lung disease were derived, highlighting their relevance in multiorgan disease manifestations. CONCLUSION: The clinical utility of the systemic score was shown in identifying Still disease at a higher risk of life-threatening evolution in a large cohort. Furthermore, the clinical relevance of liver involvement and lung disease was highlighted.
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Sistema de Registros , Enfermedad de Still del Adulto , Humanos , Masculino , Femenino , Adulto , Estudios Prospectivos , Persona de Mediana Edad , Enfermedad de Still del Adulto/diagnóstico , Enfermedad de Still del Adulto/complicaciones , Adulto Joven , Índice de Severidad de la Enfermedad , Pronóstico , Progresión de la Enfermedad , Síndrome de Activación Macrofágica/diagnósticoRESUMEN
Objective: Inflammation has been associated with an increased risk for cancer development, while innate immune system activation could counteract the risk for malignancies. Familial Mediterranean fever (FMF) is a severe systemic inflammatory condition and also represents the archetype of innate immunity deregulation. Therefore, the aim of this study is to investigate the risk for cancer development in FMF. Methods: The risk ratio (RR) for malignancies was separately compared between FMF patients and fibromyalgia subjects, Still's disease patients and Behçet's disease patients. Clinical variables associated with cancer development in FMF patients were searched through binary logistic regression. Results: 580 FMF patients and 102 fibromyalgia subjects, 1012 Behçet's disease patients and 497 Still's disease patients were enrolled. The RR for the occurrence of malignant neoplasms was 0.26 (95% Confidence Interval [CI.] 0.10-0.73, p=0.006) in patients with FMF compared to fibromyalgia subjects; the RR for the occurrence of malignant cancer was 0.51 (95% CI. 0.23-1.16, p=0.10) in FMF compared to Still's disease and 0.60 (95% CI. 0.29-1.28, p=0.18) in FMF compared to Behçet's disease. At logistic regression, the risk of occurrence of malignant neoplasms in FMF patients was associated with the age at disease onset (ß1 = 0.039, 95% CI. 0.001-0.071, p=0.02), the age at the diagnosis (ß1 = 0.048, 95% CI. 0.039-0.085, p=0.006), the age at the enrolment (ß1 = 0.05, 95% CI. 0.007-0.068, p=0.01), the number of attacks per year (ß1 = 0.011, 95% CI. 0.001- 0.019, p=0.008), the use of biotechnological agents (ß1 = 1.77, 95% CI. 0.43-3.19, p=0.009), the use of anti-IL-1 agents (ß1 = 2.089, 95% CI. 0.7-3.5, p=0.002). Conclusions: The risk for cancer is reduced in Caucasic FMF patients; however, when malignant neoplasms occur, this is more frequent in FMF cases suffering from a severe disease phenotype and presenting a colchicine-resistant disease.
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Fiebre Mediterránea Familiar , Neoplasias , Sistema de Registros , Humanos , Fiebre Mediterránea Familiar/complicaciones , Fiebre Mediterránea Familiar/epidemiología , Neoplasias/epidemiología , Neoplasias/etiología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Factores de Riesgo , Estudios de Cohortes , Adulto Joven , Fibromialgia/epidemiología , Fibromialgia/etiología , Síndrome de Behçet/epidemiología , Síndrome de Behçet/complicacionesRESUMEN
INTRODUCTION: Since many biological drug patents have expired, biosimilar agents (BIOs) have been developed; however, there are still some reservations in their use, especially in childhood. The aim of the current study is to evaluate the efficacy and safety of tumor necrosis factor (TNF) inhibitors BIOs as treatment for pediatric non-infectious uveitis (NIU). METHODS: Data from pediatric patients with NIU treated with TNF inhibitors BIOs were drawn from the international AutoInflammatory Disease Alliance (AIDA) registries dedicated to uveitis and Behçet's disease. The effectiveness and safety of BIOs were assessed in terms of frequency of relapses, risk for developing ocular flares, best-corrected visual acuity (BCVA), glucocorticoids (GCs)-sparing effect, drug survival, frequency of ocular complications, and adverse drug event (AE). RESULTS: Forty-seven patients (77 affected eyes) were enrolled. The BIOs employed were adalimumab (ADA) (89.4%), etanercept (ETA) (5.3%), and infliximab (IFX) (5.3%). The number of relapses 12 months prior to BIOs and at last follow-up was 282.14 and 52.43 per 100 patients/year. The relative risk of developing ocular flares before BIOs introduction compared to the period following the start of BIOs was 4.49 (95% confidence interval [CI] 3.38-5.98, p = 0.004). The number needed to treat (NNT) for ocular flares was 3.53. Median BCVA was maintained during the whole BIOs treatment (p = 0.92). A significant GCs-sparing effect was observed throughout the treatment period (p = 0.002). The estimated drug retention rate (DRR) at 12-, 24-, and 36-month follow-up were 92.7, 83.3, and 70.8%, respectively. The risk rate for developing structural ocular complications was 89.9/100 patients/year before starting BIOs and 12.7/100 patients/year during BIOs treatment, with a risk ratio of new ocular complications without BIOs of 7.1 (CI 3.4-14.9, p = 0.0003). Three minor AEs were reported. CONCLUSIONS: TNF inhibitors BIOs are effective in reducing the number of ocular uveitis relapses, preserving visual acuity, allowing a significant GCs-sparing effect, and preventing structural ocular complications. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT05200715.
RESUMEN
Behcet's disease is a chronic multi-system disorder of unknown etiology with protean manifestations. Venous thromboembolism is more common than arterial thrombosis, with deep vein thrombosis being the most frequent. Endothelial dysfunction resulting from vascular inflammation is considered to be an important factor of thrombosis, although the endothelial injury itself cannot completely explain the hypercoagulable state of the disease because other vasculitis syndromes do not increase the risk of thrombosis. The aim of this study is to evaluate the prevalence of activated protein C resistance (APC-R) in Egyptian patients with Behcet's disease. Also, to detect hyperhomocysteinemia in selected cases (with vascular complications) to assess their relationship with thromboembolic complications. The APC resistance ratio mean in the group of patients with vascular involvement was 2.6 ± 0.8 which was less than the group with no vascular involvement 2.8 ± 0.6, with non- significant P-value (0.5). There was more incidence of ocular lesions in the group of patients with high homocysteine level than the group of patients with normal homocytsteine level with significant P-value (0.08).