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1.
BMC Infect Dis ; 21(1): 659, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34233631

RESUMO

BACKGROUND: Pneumocystis pneumonia (PCP) severely menaces modern chemotherapy and immunosuppression. Detailed description of the epidemiology of Pneumocystis jirovecii today is needed to identify candidates for PCP-prophylaxis. METHODS: We performed a 12-year retrospective study of patients with P. jirovecii detected by polymerase chain reaction in Central Norway. In total, 297 patients were included. Comprehensive biological, clinical and epidemiological data were abstracted from patients' medical records. Regional incidence rates and testing trends were also assessed. RESULTS: From 2007 to 2017 we found a 3.3-fold increase in testing for P. jirovecii accompanied by a 1.8-fold increase in positive results. Simultaneously, regional incidence rates doubled from 5.0 cases per 100,000 person years to 10.8. A majority of the study population had predisposing conditions other than human immunodeficiency virus (HIV). Hematological (36.0%) and solid cancers (25.3%) dominated. Preceding corticosteroids were a common denominator for 72.1%. Most patients (74.4%) presented with at least two cardinal symptoms; cough, dyspnea or fever. Main clinical findings were hypoxia, cytopenias and radiological features consistent with PCP. A total of 88 (29.6%) patients required intensive care and 121 (40.7%) suffered at least one complication. In-hospital mortality was 21.5%. Three patients (1.0%) had received prophylaxis. CONCLUSIONS: P. jirovecii is re-emerging; likely due to increasing immunosuppressants use. This opportunistic pathogen threatens the life of heterogenous non-HIV immunosuppressed populations currently at growth. Corticosteroids seem to be a major risk factor. A strategy to increase prophylaxis is called for.


Assuntos
Hospedeiro Imunocomprometido , Imunossupressores/administração & dosagem , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/mortalidade , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Idoso , Feminino , Infecções por HIV/epidemiologia , Neoplasias Hematológicas/epidemiologia , Mortalidade Hospitalar , Humanos , Imunossupressores/uso terapêutico , Incidência , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Pneumocystis carinii/genética , Pneumonia por Pneumocystis/microbiologia , Reação em Cadeia da Polimerase , Estudos Retrospectivos , Fatores de Risco
2.
Molecules ; 26(11)2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34205169

RESUMO

In humans, various sites like cannabinoid receptors (CBR) having a binding affinity with cannabinoids are distributed on the surface of different cell types, where endocannabinoids (ECs) and derivatives of fatty acid can bind. The binding of these substance(s) triggers the activation of specific receptors required for various physiological functions, including pain sensation, memory, and appetite. The ECs and CBR perform multiple functions via the cannabinoid receptor 1 (CB1); cannabinoid receptor 2 (CB2), having a key effect in restraining neurotransmitters and the arrangement of cytokines. The role of cannabinoids in the immune system is illustrated because of their immunosuppressive characteristics. These characteristics include inhibition of leucocyte proliferation, T cells apoptosis, and induction of macrophages along with reduced pro-inflammatory cytokines secretion. The review seeks to discuss the functional relationship between the endocannabinoid system (ECS) and anti-tumor characteristics of cannabinoids in various cancers. The therapeutic potential of cannabinoids for cancer-both in vivo and in vitro clinical trials-has also been highlighted and reported to be effective in mice models in arthritis for the inflammation reduction, neuropathic pain, positive effect in multiple sclerosis and type-1 diabetes mellitus, and found beneficial for treating in various cancers. In human models, such studies are limited; thereby, further research is indispensable in this field to get a conclusive outcome. Therefore, in autoimmune disorders, therapeutic cannabinoids can serve as promising immunosuppressive and anti-fibrotic agents.


Assuntos
Doenças Autoimunes do Sistema Nervoso/metabolismo , Endocanabinoides/metabolismo , Receptores de Canabinoides/metabolismo , Animais , Doenças Autoimunes do Sistema Nervoso/tratamento farmacológico , Citocinas/metabolismo , Endocanabinoides/farmacologia , Endocanabinoides/uso terapêutico , Humanos , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Leucócitos/metabolismo , Receptores de Canabinoides/efeitos dos fármacos , Linfócitos T/metabolismo
3.
BMJ Case Rep ; 14(7)2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34290027

RESUMO

Autoimmune hepatitis (AIH) is a rare chronic liver disease with a non-specific clinical presentation. Its physiopathology is not fully understood and, if untreated, can progress to cirrhosis and even fulminant liver failure. Here, we describe a case of a 73-year-old patient with an 11-month history suggestive of liver disease, who was concomitantly diagnosed with AIH and the extremely rare postinfantile giant cell hepatitis (PIGCH). Despite standard immunosuppressive therapy, the patient presented a severe clinical course, culminating in acute-on-chronic liver failure and death. This case reminds physicians of the importance of an early diagnosis, close monitoring and timely treatment of AIH. It also highlights the significant role in prognosis of the specific histological pattern of PIGCH, which has been mainly associated with a serious clinical outcome and unpredictable response to immunosuppressive therapy. Triggers of both AIH and PIGCH, such as viral infections, must be excluded, given their treatment implications.


Assuntos
Hemocromatose , Hepatite Autoimune , Idoso , Hepatite Autoimune/complicações , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Prognóstico
4.
Paediatr Drugs ; 23(4): 331-347, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34244988

RESUMO

Childhood-onset systemic lupus erythematosus (cSLE) is a prototype of a multisystemic, inflammatory, heterogeneous autoimmune condition. This disease is characterized by simultaneous or sequential organ and system involvement, with unpredictable flare and high levels of morbidity and mortality. Racial/ethnic background, socioeconomic status, cost of medications, difficulty accessing health care, and poor adherence seem to impact lupus outcomes and treatment response. In this article, the management of cSLE patients is updated. Regarding pathogenesis, a number of potential targets for drugs have been studied. However, most treatments in pediatric patients are off-label drugs with recommendations based on inadequately powered studies, therapeutic consensus guidelines, or case series. Management practices for cSLE patients include evaluations of disease activity and cumulative damage scores, routine non-live vaccinations, physical activity, and addressing mental health issues. Antimalarials and glucocorticoids are still the most common drugs used to treat cSLE, and hydroxychloroquine is recommended for nearly all cSLE patients. Disease-modifying antirheumatic drugs (DMARDs) should be standardized for each patient, based on disease flare and cSLE severity. Mycophenolate mofetil or intravenous cyclophosphamide is suggested as induction therapy for lupus nephritis classes III and IV. Calcineurin inhibitors (cyclosporine, tacrolimus, voclosporin) appear to be another good option for cSLE patients with lupus nephritis. Regarding B-cell-targeting biologic agents, rituximab may be used for refractory lupus nephritis patients in combination with another DMARD, and belimumab was recently approved by the US Food and Drug Administration for cSLE treatment in children aged > 5 years. New therapies targeting CD20, such as atacicept and telitacicept, seem to be promising drugs for SLE patients. Anti-interferon therapies (sifalimumab and anifrolumab) have shown beneficial results in phase II randomized control trials in adult SLE patients, as have some Janus kinase inhibitors, and these could be alternative treatments for pediatric patients with severe interferon-mediated inflammatory disease in the future. In addition, strict control of proteinuria and blood pressure is required in cSLE, especially with angiotensin-converting enzyme inhibitor and angiotensin receptor blocker use.


Assuntos
Gerenciamento Clínico , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Idade de Início , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Criança , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Imunoterapia/métodos , Lúpus Eritematoso Sistêmico/imunologia , Ácido Micofenólico/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
BMC Nephrol ; 22(1): 251, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34229622

RESUMO

BACKGROUND: The ongoing coronavirus pandemic has major impacts on both patients and healthcare systems worldwide, thus creating new realities. Patients on maintenance dialysis listed for renal transplantation are a vulnerable subgroup with many comorbidities and recurring contacts with the healthcare system. Due to the COVID-19 pandemic transplant numbers have dropped considerably, further increasing waiting times in this high-risk population. On the other hand, knowledge of the severity of SARS-CoV-2 infection in immunocompromised patients, development and persistence of neutralising antibodies in such patients is just emerging. It is unclear how best to address the dilemma of postponing the life-saving transplantation. CASE PRESENTATION: We present a case report of a successful kidney transplantation only 65 days after the recipient was hospitalized for treatment of COVID-19 pneumonia. In a follow up of 9 months, we observed no signs of recurrent disease and transplant function is excellent. Monitoring SARS-CoV-2 antibody response demonstrates stable IgG levels. CONCLUSION: This reassuring case provides guidance to transplant centers how to proceed with kidney transplantation safely during the pandemic. Careful consideration of risks and benefits of the organ offer, full recovery from COVID-19 symptoms and the presence of a positive SARS-CoV-2 IgG antibody test, qualifies for kidney transplantation.


Assuntos
Anticorpos Antivirais/imunologia , COVID-19/imunologia , Falência Renal Crônica/cirurgia , Transplante de Rim , Idoso , COVID-19/complicações , Teste Sorológico para COVID-19 , Feminino , Rejeição de Enxerto/prevenção & controle , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Imunossupressores/uso terapêutico , Falência Renal Crônica/complicações , Diálise Renal , SARS-CoV-2
6.
Sci Rep ; 11(1): 11462, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34075090

RESUMO

An excessive immune response known as cytokine storm is the hallmark of severe COVID-19. The cause of this cytokine rampage is yet not known. Based on recent epidemiological evidence, we hypothesized that CD80/86 signaling is essential for this hyperinflammation, and that blocking this proinflammatory axis could be an effective therapeutic approach to protect against severe COVID-19. Here we provide exploratory evidence that abatacept, a drug that blocks CD80/86 co-stimulation, produces changes at the systemic level that are highly antagonistic of the proinflammatory processes elicited by COVID-19. Using RNA-seq from blood samples from a longitudinal cohort of n = 38 rheumatic patients treated with abatacept, we determined the immunological processes that are significantly regulated by this treatment. We then analyzed available blood RNA-seq from two COVID19 patient cohorts, a very early cohort from the epicenter of the pandemic in China (n = 3 COVID-19 cases and n = 3 controls), and a recent and larger cohort from the USA (n = 49 severe and n = 51 mild COVD-19 patients). We found a highly significant antagonism between SARS-CoV-2 infection and COVID-19 severity with the systemic response to abatacept. Analysis of previous single-cell RNA-seq data from bronchoalveolar lavage fluid from mild and severe COVID-19 patients and controls, reinforce the implication of the CD80/86 proinflammatory axis. Our functional results further support abatacept as a candidate therapeutic approach to prevent severe COVID-19.


Assuntos
Abatacepte/farmacologia , COVID-19/tratamento farmacológico , Síndrome da Liberação de Citocina/prevenção & controle , Imunossupressores/farmacologia , SARS-CoV-2/imunologia , Transdução de Sinais/efeitos dos fármacos , Abatacepte/uso terapêutico , Idoso , Artrite Reumatoide/sangue , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Antígeno B7-1/metabolismo , Antígeno B7-2/metabolismo , Líquido da Lavagem Broncoalveolar/citologia , COVID-19/sangue , COVID-19/complicações , COVID-19/imunologia , China , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/virologia , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , RNA-Seq , Índice de Gravidade de Doença , Transdução de Sinais/imunologia , Análise de Célula Única , Espanha , Estados Unidos , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/imunologia
7.
Rev Saude Publica ; 55: 33, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34076208

RESUMO

OBJECTIVE: To estimate the prevalence and variability of nonadherence to immunosuppressives and nonpharmacological treatment across kidney transplantation centers and two health access-disparate regions in Brazil. METHODS: In a cross-sectional design, a random multistage sample of 1,105 patients was included, based on center transplantation activity (low/moderate/high) and region (R1: North/Northeast/Mid-West; and R2: South/Southeast). Nonadherence to immunosuppressives (implementation phase) was assessed using the Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS)©. Self-report questionnaires assessed nonadherence to physical activity, smoking cessation, alcohol intake, and appointment keeping. We compared regions using the adjusted-χ2 or t-test. RESULTS: Most patients were men (58.5%), white (51.4%), and had a mean age of 47.5 (SD = 12.6) years. Regarding kidney transplantation centers, 75.9% were from R2 and 38.2% had low activity. The patients in R2 were older, white-majority, had more frequently steady partners, and received peritoneal dialysis. Nonadherence to immunosuppressives ranged from 11-65.2%; 44.5-90% to physical activity; 0-23.7% to appointment keeping; and 0-14% to smoking cessation. The total prevalence of nonadherence and by region (R1 versus R2) were: for immunosuppressives, 39.7% (44.9% versus 38.1%, p = 0.18); for smoking, 3.9% (1% versus 5%, p < 0.001); for physical activity, 69.1% (71% versus 69%, p = 0.48); for appointment keeping, 13% (12.7% versus 12%, p = 0.77); and for alcohol consumption, 0%. CONCLUSION: Despite differences among centers and high variability, only the nonadherence to smoking cessation was higher in the region with greater access to kidney transplantation. We suppose that differences in healthcare access may have been overcome by other positive aspects of the post kidney transplantation treatment.


Assuntos
Transplante de Rim , Brasil , Estudos Transversais , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Adesão à Medicação , Pessoa de Meia-Idade
8.
Int J Mol Sci ; 22(11)2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34063776

RESUMO

Calcineurin inhibitors are highly efficacious immunosuppressive agents used in pediatric kidney transplantation. However, calcineurin inhibitor nephrotoxicity (CNIT) has been associated with the development of chronic renal allograft dysfunction and decreased graft survival. This study evaluated 37 formalin-fixed paraffin-embedded biopsies from pediatric kidney transplant recipients using gene expression profiling. Normal allograft samples (n = 12) served as negative controls and were compared to biopsies exhibiting CNIT (n = 11). The remaining samples served as positive controls to validate CNIT marker specificity and were characterized by other common causes of graft failure such as acute rejection (n = 7) and interstitial fibrosis/tubular atrophy (n = 7). MiRNA profiles served as the platform for data integration. Oxidative phosphorylation and mitochondrial dysfunction were the top molecular pathways associated with overexpressed genes in CNIT samples. Decreased ATP synthesis was identified as a significant biological function in CNIT, while key toxicology pathways included NRF2-mediated oxidative stress response and increased permeability transition of mitochondria. An integrative analysis demonstrated a panel of 13 significant miRNAs and their 33 CNIT-specific gene targets involved with mitochondrial activity and function. We also identified a candidate panel of miRNAs/genes, which may serve as future molecular markers for CNIT diagnosis as well as potential therapeutic targets.


Assuntos
Biomarcadores/metabolismo , Inibidores de Calcineurina/toxicidade , Sobrevivência de Enxerto/genética , Nefropatias/induzido quimicamente , Nefropatias/genética , Transcriptoma/genética , Biópsia/métodos , Inibidores de Calcineurina/uso terapêutico , Criança , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/genética , Humanos , Imunossupressores/uso terapêutico , Imunossupressores/toxicidade , Rim/efeitos dos fármacos , Rim/metabolismo , Transplante de Rim/efeitos adversos , MicroRNAs/genética , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Transplantados , Transplante Homólogo/métodos
9.
Saudi J Kidney Dis Transpl ; 32(1): 218-222, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34145134

RESUMO

Underlying comorbid illness is a known risk factor for severe coronavirus disease-2019 (COVID-19). Clinical course of COVID-19 in children with primary kidney disease is not well understood. We present the clinical profile and management of COVID-19 in three children at a COVID hospital in India. These children had nephrotic syndrome, hemolytic uremic syndrome, and chronic kidney disease, respectively. The first two were immunosuppressed, mandating to stop their immunosuppressive medications temporarily. Both had mild course of illness. Third child presented with respiratory distress requiring oxygen support, falling into moderate disease. Renal functions were normal in all of them. They all responded well to oral azithromycin and supportive management. None of them received chloroquine, corticosteroids, or monoclonal antibodies. All three recovered without complications.


Assuntos
COVID-19/complicações , COVID-19/terapia , Síndrome Hemolítico-Urêmica/complicações , Síndrome Nefrótica/complicações , Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Criança , Pré-Escolar , Feminino , Síndrome Hemolítico-Urêmica/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Masculino , Síndrome Nefrótica/tratamento farmacológico , Oxigenoterapia , SARS-CoV-2
10.
J Wound Care ; 30(6): 492-496, 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34121430

RESUMO

OBJECTIVE: Stevens-Johnson syndrome (SJS) and its more severe counterpart, toxic epidermal necrolysis (TEN), are skin hypersensitivity reactions defined by epidermal blistering and necrosis. The exact pathophysiology of SJS/TEN is yet to be deciphered, but a number of risk factors have been identified including adverse drug reactions. The diagnosis of SJS/TEN is made on a clinical basis, and treatment consists of supportive care and occasionally immunosuppressants, such as cyclosporin, high-dose intravenous immunoglobulins and/or corticosteroids. Mortality rates can reach 20-25% in adults but are reduced with early intervention. To identify optimal treatment regimens, to better understand the patient cohort affected, and to help identify key risk factors for mortality, we report our experience with the treatment and management of SJS/TEN patients. METHODS: A retrospective review of consecutive patients with SJS and/or TEN admitted to a single burns centre in Germany, between 2008 and 2018, was conducted. The primary outcomes of demographics, clinical course, treatment and patient-reported outcomes were recorded and compared with a control group of patients with burns without a diagnosis of SJS/TEN. RESULTS: A total of 23 patients with SJS/TEN met the inclusion criteria: 17 (74%) with TEN; four (17%) with SJS/TEN overlap; and two (9%) with SJS. Of the patients, 14 (61%) were female and nine (39%) were male. Patient age ranged from 32-78 years (mean: 52 years). A matched cohort of 23 patients with burns served as the control group. All patients received standard of care with a multidisciplinary team. Compared with the control group, SJS/TEN patients had higher mortality rates (n=6, 26% versus n=8, 35%, respectively). The average age of death was 69 years in SJS/TEN patients versus 63 years in control group patients. Age and SCORTEN scores were significant predictors of mortality. CONCLUSIONS: SJS and TEN are rare but extreme reactions of the skin and mucosa, associated with high disease mortality rates. This 10-year single-centre retrospective review contributes to the bank of information for reviews evaluating the management of SJS/TEN patients.


Assuntos
Corticosteroides/uso terapêutico , Queimaduras/terapia , Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/uso terapêutico , Síndrome de Stevens-Johnson/tratamento farmacológico , Cicatrização , Adulto , Idoso , Unidades de Queimados , Queimaduras/mortalidade , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Síndrome de Stevens-Johnson/mortalidade , Resultado do Tratamento
11.
Clin Rheumatol ; 40(8): 3185-3193, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34080081

RESUMO

OBJECTIVE: This study systematically compares the efficacy and adverse events of mycophenolate mofetil (MMF) and cyclophosphamide (CYC) in patients with systemic sclerosis-related interstitial lung disease (SSc-ILD). METHODS: The EMBASE and PubMed databases were systematically searched to find all relevant studies. Quality assessment, study selection, and data extraction were independently conducted by two reviewers. The mean changes in forced vital capacity (FVC)% and diffusing capacity for carbon monoxide (DLco)% of the patients were selected to be primary outcome measures. Stata software was used for the pooled analysis. RESULTS: Among 284 titles screened from multiple databases, six studies met the inclusion criteria (one randomized controlled trial, three prospective observational studies, and two retrospective observational studies). The summary weighted mean difference (WMD) of FVC change in the MMF group compared with the CYC group was - 1.17 (95% CI: - 2.713, 0.373; P = 0.137), and the summary WMD of DLco change in the MMF group compared with the CYC group was 2.245 (95% CI: 0.258, 4.232; P = 0.027). Studies enrolled showed that adverse events were less common in the MMF group. CONCLUSIONS: The efficacy of MMF with respect to FVC and DLco improvement is comparable to that of CYC, and MMF is preferred on the basis of the occurrence of adverse events. Key Points • A systematic review and meta-analysis was conducted to compare the efficacy and adverse events of mycophenolate mofetil and cyclophosphamide in patients with systemic sclerosis-related interstitial lung disease. • The efficacy of MMF with respect to FVC and DLco improvement is comparable to that of CYC, and MMF is preferred on the basis of the occurrence of adverse events.


Assuntos
Doenças Pulmonares Intersticiais , Escleroderma Sistêmico , Ciclofosfamida/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Ácido Micofenólico/uso terapêutico , Estudos Observacionais como Assunto , Estudos Retrospectivos , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/tratamento farmacológico , Resultado do Tratamento
12.
J Immunother Cancer ; 9(6)2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34117116

RESUMO

SARS-CoV-2 is the virus responsible for the COVID-19 pandemic. COVID-19 has highly variable disease severity and a bimodal course characterized by acute respiratory viral infection followed by hyperinflammation in a subset of patients with severe disease. This immune dysregulation is characterized by lymphocytopenia, elevated levels of plasma cytokines and proliferative and exhausted T cells, among other dysfunctional cell types. Immunocompromised persons often fare worse in the context of acute respiratory infections, but preliminary data suggest this may not hold true for COVID-19. In this review, we explore the effect of SARS-CoV-2 infection on mortality in four populations with distinct forms of immunocompromise: (1) persons with hematological malignancies (HM) and hematopoietic stem cell transplant (HCT) recipients; (2) solid organ transplant recipients (SOTRs); (3) persons with rheumatological diseases; and (4) persons living with HIV (PLWH). For each population, key immunological defects are described and how these relate to the immune dysregulation in COVID-19. Next, outcomes including mortality after SARS-CoV-2 infection are described for each population, giving comparisons to the general population of age-matched and comorbidity-matched controls. In these four populations, iatrogenic or disease-related immunosuppression is not clearly associated with poor prognosis in HM, HCT, SOTR, rheumatological diseases, or HIV. However, certain individual immunosuppressants or disease states may be associated with harmful or beneficial effects, including harm from severe CD4 lymphocytopenia in PLWH and possible benefit to the calcineurin inhibitor ciclosporin in SOTRs, or tumor necrosis factor-α inhibitors in persons with rheumatic diseases. Lastly, insights gained from clinical and translational studies are explored as to the relevance for repurposing of immunosuppressive host-directed therapies for the treatment of hyperinflammation in COVID-19 in the general population.


Assuntos
COVID-19 , Reposicionamento de Medicamentos , Hospedeiro Imunocomprometido , Imunossupressores/uso terapêutico , Imunoterapia , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/terapia , Comorbidade , Reposicionamento de Medicamentos/métodos , Reposicionamento de Medicamentos/estatística & dados numéricos , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Humanos , Hospedeiro Imunocomprometido/fisiologia , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Imunoterapia/estatística & dados numéricos , Mortalidade , Pandemias , Prognóstico , Doenças Reumáticas/epidemiologia , SARS-CoV-2/fisiologia , Transplantados/estatística & dados numéricos
13.
Int J Mol Sci ; 22(11)2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34071155

RESUMO

Myasthenia gravis (MG) is an autoimmune disease in which immunoglobulin G (IgG) antibodies (Abs) bind to acetylcholine receptors (AChR) or to functionally related molecules in the postsynaptic membrane at the neuromuscular junction. IgG crystallizable fragment (Fc)-mediated effector functions, such as antibody-dependent complement deposition, contribute to disease development and progression. Despite progress in understanding Ab-mediated disease mechanisms, immunotherapy of MG remained rather unspecific with corticosteroids and maintenance with immunosuppressants as first choice drugs for most patients. More specific therapeutic IgG Fc-based platforms that reduce serum half-life or effector functions of pathogenic MG-related Abs are currently being developed, tested in clinical trials or have recently been successfully translated into the clinic. In this review, we illustrate mechanisms of action and clinical efficacies of emerging Fc-mediated therapeutics such as neonatal Fc receptor (FcRn)-targeting agents. Furthermore, we evaluate prospects of therapies targeting classical Fc receptors that have shown promising therapeutic efficacy in other antibody-mediated conditions. Increased availability of Fc- and Fc receptor-targeting biologics might foster the development of personalized immunotherapies with the potential to induce sustained disease remission in patients with MG.


Assuntos
Miastenia Gravis/tratamento farmacológico , Receptores Fc/química , Receptores Fc/efeitos dos fármacos , Animais , Autoanticorpos/imunologia , Antígenos de Histocompatibilidade Classe I , Humanos , Fragmentos Fc das Imunoglobulinas/farmacologia , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Imunoglobulina G/imunologia , Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Imunoterapia , Miastenia Gravis/fisiopatologia , Medicina de Precisão , Receptores Colinérgicos/imunologia
14.
Medicine (Baltimore) ; 100(22): e25688, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087822

RESUMO

RATIONALE: Hydroxychloroquine has excellent anti-inflammatory and immunomodulatory effects as one of the antimalarial drugs. In particular, hydroxychloroquine was once widely used as a treatment for the new coronavirus pneumonia epidemic in 2020. Retinopathy caused by hydroxychloroquine is normally irreversible, but little attention has been paid to it. PATIENT CONCERNS: A 38-year-old young Chinese woman was taking oral hydroxychloroquine 400 mg daily to control lupus disease activity for six years after the diagnosis of systemic lupus erythematosus (SLE). She did not have any history of eye disease and was admitted to the hospital with a sudden blurring of both eyes. DIAGNOSES: The diagnosis of retinal macular degeneration caused by hydroxychloroquine was made after excluding other interfering diseases based on the patient's long-term use of hydroxychloroquine and the results of the eye examination. INTERVENTIONS: The patient was discontinued from hydroxychloroquine. To control the recurrence of SLE, she was given intravenous methylprednisolone, oral tacrolimus and mycophenolate. Meanwhile, she was asked to take extra care of her eyes and to come to the hospital every three months to have her vision checked. OUTCOMES: The patient's blurred vision improved one week later. Three months later, her vision examination showed no further decline (0.4 in the right eye and 0.6 in the left eye). Meanwhile, the SLE disease activity index (SLEDAI) decreased from six points to five points currently. LESSONS: Retinopathy caused by hydroxychloroquine is irreversible and there is no particularly effective treatment. Discontinuation of hydroxychloroquine, better daily eye protection, and regular vision checks are the keys to preventing retinopathy. Although hydroxychloroquine causing retinal toxicity was mentioned several years ago, the rate and severity of retinal toxicity require further research. How to get more patients to take care of their eyes requires continuous and increased education by doctors.


Assuntos
Anti-Inflamatórios/efeitos adversos , Hidroxicloroquina/efeitos adversos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Doenças Retinianas/induzido quimicamente , Adulto , Anti-Inflamatórios/uso terapêutico , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Imunossupressores/uso terapêutico , Acuidade Visual
15.
BMJ Case Rep ; 14(6)2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34155028

RESUMO

Acquired haemophilia A (AHA) is a rare and possibly fatal autoimmune disorder that is challenging to treat. Although a majority of cases are idiopathic, AHA can also be associated with an underlying malignancy, autoimmune disorder, pregnancy, infection or certain medications. The diagnosis and treatment of AHA require a specialist with both clinical and laboratory expertise. The goal of treatment is aimed at achieving haemostasis as well as eradicating factor inhibitors. We present a patient with AHA and life-threatening haemorrhage who was successfully treated with a combination of haemostatic agents and a triple-drug immunosuppressive regimen. In reviewing recent studies and published guidelines, we advocate that a newer agent, emicizumab, can potentially be incorporated into the treatment protocol for AHA given its promising performance in the realm of congenital haemophilia.


Assuntos
Hemofilia A , Hemostáticos , Feminino , Hemofilia A/diagnóstico , Hemofilia A/tratamento farmacológico , Hemorragia , Hemostáticos/uso terapêutico , Humanos , Imunossupressão , Imunossupressores/uso terapêutico , Gravidez
16.
Autoimmun Rev ; 20(8): 102872, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34118459

RESUMO

OBJECTIVE: To describe the prevalence, clinical presentation and current treatment regimens of inflammatory bowel disease (IBD) in patients with primary immunodeficiency disorders (PIDs). METHODS: A systematic review was conducted. The following databases were searched: MEDLINE, Embase, Web of Science, the Cochrane Library and Google Scholar. RESULTS: A total of 838 articles were identified, of which 36 were included in this review. The prevalence of IBD in PIDs ranges between 3.4% and 61.2%, depending on the underlying PID. Diarrhea and abdominal pain were reported in 64.3% and 52.4% of the patients, respectively. Colon ulceration was the most frequent finding on endoscopic evaluation, while cryptitis, granulomas, ulcerations and neutrophilic/lymphocytic infiltrates were the most frequently reported histopathological abnormalities. Described treatment regimens included oral corticosteroids and other oral immunosuppressive agents, including mesalazine, azathioprine and cyclosporin, leading to clinical improvement in the majority of patients. In case of treatment failure, biological therapies including TNF- α blocking agents, are considered. CONCLUSIONS: The overall prevalence of IBD in patients with PID is high, but varies between different PIDs. Physicians should be aware of these complications and focus on characteristic symptoms to reduce diagnostic delay and delay in initiation of treatment. Treatment of IBD in PIDs depends on severity of symptoms and may differ between various PIDs based on distinct underlying pathogenesis. An individualized diagnostic and therapeutic approach is therefore warranted.


Assuntos
Doenças Inflamatórias Intestinais , Doenças da Imunodeficiência Primária , Azatioprina , Diagnóstico Tardio , Humanos , Imunossupressores/uso terapêutico , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/tratamento farmacológico
17.
Rheumatol Int ; 41(8): 1523-1529, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34100115

RESUMO

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) are systemic autoimmune diseases that may lead to renal failure due to the infiltration of mononuclear cells and the destruction of small- and medium-sized blood vessels. It has been shown that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may trigger the presentation or exacerbation of autoimmune diseases. Crescentic glomerulonephritis (GN) has rarely been reported in patients with Coronavirus disease-2019 (COVID-19). We present rare two cases with AAV after a recent diagnosis of COVID-19. The first case was 26-year-old male patient, who was presented with acute kidney injury after COVID-19. Serum creatinine increased and active urine sediment was seen. Serological evaluation showed anti-myeloperoxidase antibody was at a level of 80.6 U/mL. Kidney biopsy showed necrotizing GN with cellular crescents. Methylprednisolone, cyclophosphamide and plasma exchange were administered. He was discharged with hemodialysis. Second case was a 36-year-old female who was hospitalized because of fever, cough and dyspnea. After she was diagnosed with COVID-19, she had total hearing loss, with cavitary lesions on bilateral lung parenchyma and an acute kidney injury. Serological evaluation showed an elevated anti-proteinase-3 with a level of 1:32. Kidney biopsy showed necrotizing GN with cellular crescents. Renal function improved after methylprednisolone and cyclophosphamide treatment. With a systematic review of the literature, we found four cases of new-onset AAV due to COVID-19. Herein, we discuss two cases and provide a literature review on cases of new-onset pauci-immune GN after COVID-19 infection.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , COVID-19/imunologia , SARS-CoV-2/imunologia , Adulto , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia , COVID-19/diagnóstico , COVID-19/virologia , Feminino , Interações Hospedeiro-Patógeno , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Troca Plasmática , Diálise Renal , SARS-CoV-2/patogenicidade , Resultado do Tratamento
18.
Rheumatol Int ; 41(8): 1441-1445, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34142203

RESUMO

Patients with rheumatic and musculoskeletal (RMD) diseases may be at higher risks for COVID-19 infection. Data on the safety of the adenoviral vector-borne ChAdOx1 nCoV-19 and the heat-inactivated BBV152 Vaccines in this group are limited. 724 patients with RMD who had received at least one dose of either the ChAdOx1 or the BBV152 were audited to find out post-vaccination adverse effect (AE) or disease flares. The AE rates in patients with autoimmune rheumatic disease (AIRD) were compared with those with non-AIRD RMDs. The mean age of the cohort was 59.9 (± 10.43) years with a female (n = 581; 80.24%) majority. 523 (70.8%) had AIRD. The ChAdOx1 and the BBV152 vaccines were received by 624 (86.18%) and 77 (10.63%), respectively. 23 (3.17%) were unaware of which vaccine they had received. 238 (32.87%) of patients had at least one comorbidity. 436 (60.22%) participants [306 (59.64%) of those with AIRD and 130 (61.61%) with other RMDs] had at least one adverse effect (AE). Four patients reported flare of arthritis that resolved within 5 days. No patient had any severe AE or required hospitalization. All AEs were self-limiting. Both the ChAdOx1 and the BBV152 vaccines appear safe in RMDs. AEs do not differ between patients with AIRD or non-AIRD. This information can help negate vaccine hesitancy amongst all stakeholders.


Assuntos
Autoimunidade , Vacinas contra COVID-19/administração & dosagem , Doenças Reumáticas/imunologia , Idoso , Autoimunidade/efeitos dos fármacos , Vacinas contra COVID-19/efeitos adversos , Estudos Transversais , Feminino , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Doenças Reumáticas/diagnóstico , Doenças Reumáticas/tratamento farmacológico , Vacinação , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/efeitos adversos
19.
Medicine (Baltimore) ; 100(24): e26377, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-34128898

RESUMO

INTRODUCTION: On the basis of the results of the IMBRAVE-150 trial, the combination of atezolizumab, a programmed cell death ligand 1 (PD-L1) antibody, as well as bevacizumab, a vascular endothelial growth factor (VEGF) antibody, represents a promising novel first-line therapy in patients with advanced hepatocellular carcinoma (HCC). Despite favorable safety data, serious adverse events have been described. However, central nervous system complications such as encephalitis have rarely been reported. We present the case of a 70-year-old woman with hepatitis C virus (HCV)-related liver cirrhosis and advanced HCC who developed severe encephalitis after only one cycle of atezolizumab/bevacizumab. PATIENT CONCERNS: Ten days after administration, the patient presented with confusion, somnolence, and emesis. Within a few days, the patient's condition deteriorated, and mechanical ventilation became necessary. DIAGNOSIS: Cerebrospinal fluid (CSF) analysis showed increased cell count and elevated protein values. Further work-up revealed no signs of an infectious, paraneoplastic, or other autoimmune cause. INTERVENTION: Suspecting an atezolizumab/bevacizumab-related encephalitis, we initiated a high-dose steroid pulse therapy as well as repeated plasmapheresis, which resulted in clinical improvement and remission of CSF abnormalities. OUTCOME: Despite successful weaning and transfer to a rehabilitation ward, the patient died of progressive liver cancer 76 days after initial treatment with atezolizumab/bevacizumab, showing no response. CONCLUSION: This case illustrates that rapid immunosuppressive treatment with prednisolone can result in remission even of severe encephalitis. We discuss this case in the context of available literature and previously reported cases of atezolizumab-induced encephalitis in different tumor entities, highlighting the diagnostic challenges in oncologic patients treated with immune checkpoint-inhibitors.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Bevacizumab/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Encefalite/induzido quimicamente , Neoplasias Hepáticas/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Encefalite/terapia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Plasmaferese , Prednisolona/uso terapêutico
20.
BMJ Case Rep ; 14(6)2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34183316

RESUMO

Severe cases of the new COVID-19 are being reported in immunosuppressed patients. The risk seems to depend on the type of immunosuppressive agents used and it is particularly important in patients under the long-lasting effect of rituximab. Information regarding the best therapeutic approach to these patients is scarce and further studies are needed. We present a case of a young woman with rheumatoid arthritis treated with rituximab (last administration 4 months before her admission). She presented with a deteriorating and prolonged SARS-CoV-2 infection, with persistent fever, significant elevation of inflammatory markers and radiological progression. Glucocorticoids and antibiotic therapy were initiated, with no response. Intravenous immunoglobulin was then used with a rapid and exuberant response, anticipating a promising role of this therapy in immunosuppressed patients with COVID-19 under the effect of rituximab.


Assuntos
COVID-19 , Imunoglobulinas Intravenosas , Feminino , Humanos , Imunossupressores/uso terapêutico , Rituximab/uso terapêutico , SARS-CoV-2
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