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1.
Artigo em Chinês | MEDLINE | ID: mdl-33535350

RESUMO

Silicosis is caused by long-term exposure to dust containing crystalline silica. However, silica exposure, which may lead to autoimmune dysfunction, is associated with autoimmune diseases such as rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus, idiopathic inflammatory myopathy and anti-central granulocyte cytoplasmic antibody associated vasculitis. With silica exposure autoimmune diseases may exist with or without silicosis. This article reviews recent research on silica-associated autoimmune diseases such as the concept, epidemiology, clinical characteristics and potential mechanisms to improve the understanding of the disease and promote the formulation of diagnostic criteria and treatment plans.


Assuntos
Doenças Autoimunes , Exposição Ocupacional , Escleroderma Sistêmico , Silicose , Doenças Autoimunes/induzido quimicamente , Poeira , Humanos , Dióxido de Silício/toxicidade
6.
Autoimmun Rev ; 19(8): 102590, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32561463

RESUMO

OBJECTIVE: To evaluate prevalence and clinical features of immune-related adverse events (irAEs) to immune checkpoint inhibitors (ICIs) in accordance with the gender of treated cancer patients. METHODS: A systematic review of the medical literature was conducted by searching all available clinical data up to December 2019 in several databases using a combination of MESH terms related to immune checkpoint inhibitors, autoimmunity, and gender. Analyzed data were related to all FDA approved ICIs and respective indications in cancer. RESULTS: According to data from the literature, male display a slightly lower frequencies of ICIs-related endocrinopathies compared with females, specifically thyroid dysfunction. On the contrary, ICIs-hypophysitis has been reported at higher rates among males compared with females. ICI-induced Sicca/Sjogren's syndrome showed a more frequent occurrence in men than the idiopathic primary form. No differences in gender distribution seem to arise in hematologic and gastrointestinal-irAEs. Interestingly, the gender distribution of neurologic and vascular ICIs-irAEs appears male-dominant. CONCLUSIONS: The present systematic review highlights for the first time that the distribution of patients experiencing irAEs associated with ICIs changes among the genders according to the specific drug used, the frequency of the cancer and of the autoimmune conditions in the general population.


Assuntos
Antineoplásicos , Doenças Autoimunes , Neoplasias , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/fisiopatologia , Autoimunidade , Feminino , Humanos , Masculino , Neoplasias/tratamento farmacológico , Fatores Sexuais
7.
Environ Res ; 187: 109541, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32445945

RESUMO

It has been demonstrated that metals can induce autoimmunity. However, few studies have attempted to assess and elucidate the underlying mechanisms of action. Recent research has tried to evaluate the possible interactions of the immune system with metal ions, particularly with heavy metals. Research indicates that metals have the potential to induce or promote the development of autoimmunity in humans. Metal-induced inflammation may dysregulate the hypothalamic-pituitary-adrenal (HPA) axis and thus contribute to fatigue and other non-specific symptoms characterizing disorders related to autoimmune diseases. The toxic effects of several metals are also mediated through free radical formation, cell membrane disturbance, or enzyme inhibition. There are worldwide increases in environmental metal pollution. It is therefore critical that studies on the role of metals in autoimmunity, and neuroendocrine disorders, including effects on the developing immune system and brain and the genetic susceptibility are performed. These studies can lead to efficient preventive strategies and improved therapeutic approaches. In this review, we have retrieved and commented on studies that evaluated the effects of metal toxicity on immune and endocrine-related pathways. This review aims to increase awareness of metals as factors in the onset and progression of autoimmune and neuroendocrine disorders.


Assuntos
Doenças Autoimunes , Metais Pesados , Doenças Autoimunes/induzido quimicamente , Autoimunidade , Humanos , Sistema Imunitário , Metais Pesados/toxicidade , Neuroendocrinologia
8.
Acta Diabetol ; 57(10): 1181-1192, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32318876

RESUMO

AIMS: Dipeptidyl peptidase-4, a transmembrane glycoprotein expressed in various cell types, serves as a co-stimulator molecule to influence immune response. This study aimed to investigate associations between DPP-4 inhibitors and risk of autoimmune disorders in patients with type 2 diabetes mellitus in Taiwan. METHODS: This retrospective cohort study used the nationwide data from the diabetes subsection of Taiwan National Health Insurance Research Database between January 1, 2009, and December 31, 2013. Cox proportional hazards models were developed to compare the risk of autoimmune disorders and the subgroup analyses between the DPP-4i and DPP-4i-naïve groups. RESULTS: A total of 774,198 type 2 diabetic patients were identified. The adjusted HR of the incidence for composite autoimmune disorders in DPP-4i group was 0.56 (95% CI 0.53-0.60; P < 0.001). The subgroup analysis demonstrated that the younger patients (aged 20-40 years: HR 0.47, 95% CI 0.35-0.61; aged 41-60 years: HR 0.50, 95% CI 0.46-0.55; aged 61-80 years: HR 0.63, 95% CI 0.58-0.68, P = 0.0004) and the lesser duration of diabetes diagnosed (0-5 years: HR 0.48, 95% CI 0.44-0.52; 6-10 years: HR 0.48, 95% CI 0.43-0.53; ≧ 10 years: HR 0.86, 95% CI 0.78-0.96, P < 0.0001), the more significant the inverse association of DPP-4 inhibitors with the incidence of composite autoimmune diseases. CONCLUSIONS: DPP-4 inhibitors are associated with lower risk of autoimmune disorders in type 2 diabetes mellitus patients in Taiwan, especially for the younger patients and the lesser duration of diabetes diagnosed. The significant difference was found between the four types of DPP-4 inhibitors and the risk of autoimmune diseases. This study provides clinicians with useful information regarding the use of DPP-4 inhibitors for treating diabetic patients.


Assuntos
Doenças Autoimunes/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes/induzido quimicamente , Estudos de Coortes , Bases de Dados Factuais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia , Adulto Jovem
9.
Best Pract Res Clin Endocrinol Metab ; 34(1): 101412, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32265102

RESUMO

An adjuvant is an immunological or pharmacological substance or group of substances that can be added to a given agent to enhance its effect in terms of efficacy, effectiveness and potency. Different mechanisms have been hypothesized underlying the action of the adjuvant, including boosting immune (innate and adaptive) response: this generally results in sparing the necessary amount of the agent and can potentially reduce the frequency of the needed number of therapeutic interventions. Adjuvants can be commonly found in vaccines, immunization products, mineral oils, cosmetics, silicone breast implants and other therapeutic/medical devices, being usually safe and effective. However, in a fraction of genetically susceptible and predisposed subjects, the administration of adjuvants may lead to the insurgence of serious side-effects, called "autoimmune/inflammatory syndrome by adjuvants" (ASIA) or Shoenfeld's syndrome. The present review is aimed at focusing on the "endocrine pebbles" of the mosaic of autoimmunity and of the ASIA syndrome, collecting together 54 cases of sub-acute thyroiditis, 2 cases of Hashimoto's thyroiditis, 11 cases of primary ovarian failure/primary ovarian insufficiency, 13 cases of autoimmune diabetes type 1, and 1 case of autoimmune adrenal gland insufficiency occurred after exposure to adjuvants.


Assuntos
Adjuvantes Imunológicos/efeitos adversos , Doenças Autoimunes/induzido quimicamente , Autoimunidade/efeitos dos fármacos , Doenças do Sistema Endócrino/induzido quimicamente , Doenças Autoimunes/genética , Autoimunidade/genética , Diabetes Mellitus Tipo 1/induzido quimicamente , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/imunologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/genética , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/imunologia , Doenças do Sistema Endócrino/genética , Doenças do Sistema Endócrino/imunologia , Predisposição Genética para Doença , Humanos , Fatores de Risco , Síndrome
10.
Clin Immunol ; 214: 108395, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32240819

RESUMO

Immune related adverse events (irAEs) have been observed with all checkpoint inhibitors and are very frequent. The evidences coming from experimental models of congenital or acquired deficiency of CTLA-4 or from PD-1 knock-out mice, provided all the informations to interpret the organ or systemic manifestations (endocrine, or systemic autoimmune chronic inflammatory diseases-ACIDs) observed in trials as well as in registries of cohorts treated with anti-CTLA-4 or anti-PD-1/PD-L1 inhibitors, or combination therapies. Finally the concern raised by cancers occurring in patients with autoimmune diseases (Systemic Lupus Erythematosus, Myositis, Rheumatoid Arthritis, Psoriatic Arthritis, Vasculitis, Scleroderma, Polymyalgia Rheumatica and others) and how to deal with immunotherapy was discussed. The biological knowledges acquired with the immunotherapy trials, have paved to way to better treat autoimmune diseases in patients developing cancer during the autoimmune illness. Immunotherapy without Autoimmunity is the unmet need within our reach in the future.


Assuntos
Abatacepte/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Doenças Autoimunes/induzido quimicamente , Antígeno B7-H1/antagonistas & inibidores , Antígeno CTLA-4/antagonistas & inibidores , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Tolerância a Antígenos Próprios/efeitos dos fármacos , Abatacepte/farmacologia , Abatacepte/uso terapêutico , Animais , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Artrite Experimental/imunologia , Artrite Psoriásica/imunologia , Artrite Psoriásica/terapia , Doenças Autoimunes/complicações , Doenças Autoimunes/imunologia , Subpopulações de Linfócitos B/efeitos dos fármacos , Subpopulações de Linfócitos B/imunologia , Células Clonais/imunologia , Modelos Animais de Doenças , Humanos , Inflamação , Lúpus Eritematoso Sistêmico/imunologia , Camundongos , Neoplasias/complicações , Neoplasias/imunologia , Neoplasias/terapia , Doenças Reumáticas/induzido quimicamente , Doenças Reumáticas/complicações , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Proteínas Supressoras de Tumor/fisiologia
12.
J Oncol Pharm Pract ; 26(6): 1538-1543, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32063105

RESUMO

INTRODUCTION: Nivolumab is a programmed death 1 (PD-1) inhibitor approved by the Food and Drug Administration (FDA) for the treatment of eight different cancers including metastatic melanoma. Immune checkpoint blockade may lead to a range of neurologic immune-related adverse events (irAEs) with severity varying from mild to life-threatening, including encephalitis. CASE REPORT: We describe a case of a 68-year-old man who developed alteration in mental status, physical weakness and fatigue after nine cycles of nivolumab 3 mg/kg every two weeks. These symptoms were compatible with a clinical diagnosis of autoimmune limbic encephalitis, although no specific antibodies were detected and the initial MRI was normal. MANAGEMENT AND OUTCOME: The patient received intravenous methylprednisolone 1 g daily for 5 days, which was then converted to a maintenance dose of oral prednisone. The patient made a full clinical recovery but relapsed clinically upon steroid tapering, while hypersignal in the left mesial temporal suggestive of limbic encephalitis was observed on repeated MRI. DISCUSSION: Because of the prevailing usage of nivolumab in many cancer protocols, this case highlights the importance of rapidly recognising neurological impairment in patients treated with nivolumab and of initiating very high doses of corticosteroids.


Assuntos
Doenças Autoimunes/tratamento farmacológico , Encefalite Límbica/tratamento farmacológico , Metilprednisolona/administração & dosagem , Nivolumabe/efeitos adversos , Idoso , Doenças Autoimunes/induzido quimicamente , Humanos , Encefalite Límbica/induzido quimicamente , Masculino , Melanoma/tratamento farmacológico , Nivolumabe/administração & dosagem , Prednisona/uso terapêutico
13.
Clin Immunol ; 213: 108352, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32032765

RESUMO

Mercury (Hg) is widely recognized as a neurotoxic metal, besides it can also act as a proinflammatory agent and immunostimulant, depending on individual exposure and susceptibility. Mercury exposure may arise from internal body pathways, such as via dental amalgams, preservatives in drugs and vaccines, and seafood consumption, or even from external pathways, i.e., occupational exposure, environmental pollution, and handling of metallic items and cosmetics containing Hg. In susceptible individuals, chronic low Hg exposure may trigger local and systemic inflammation, even exacerbating the already existing autoimmune response in patients with autoimmunity. Mercury exposure can trigger dysfunction of the autoimmune responses and aggravate immunotoxic effects associated with elevated serum autoantibodies titers. The purpose of the present review is to provide a critical overview of the many issues associated with Hg exposure and autoimmunity. In addition, the paper focuses on individual susceptibility and other health effects of Hg.


Assuntos
Doenças Autoimunes/induzido quimicamente , Exposição Ambiental/efeitos adversos , Mercúrio/efeitos adversos , Animais , Humanos
14.
BMJ Case Rep ; 13(2)2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32029513

RESUMO

Statin-induced necrotising autoimmune myopathy (SINAM) is a rare disease characterised by proximal muscle weakness and elevated creatine kinase levels that is usually in the thousands. Anti-3-hydroxy-3-methyl glutaryl co-enzyme A reductase (HMGCR) antibodies are associated with SINAM. Autoimmune hepatitis (AIH) is an inflammatory disease of the liver that is usually of unknown aetiology but can also be associated with concurrent extrahepatic autoimmune disorders. We are reporting a case of biopsy proven AIH associated with SINAM in a patient presenting with oropharyngeal dysphagia. The patient had elevated anti-HMGCR antibodies and anti-smooth muscle antibodies. SINAM and AIH were confirmed by muscle biopsy and liver biopsy, respectively. The patient had complete resolution of his symptoms and complete normalisation of his liver function tests after 6 months of the treatment.


Assuntos
Doenças Autoimunes/diagnóstico , Transtornos de Deglutição/etiologia , Hepatite Autoimune/diagnóstico , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Miosite/diagnóstico , Doenças Autoimunes/induzido quimicamente , Hepatite Autoimune/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Miosite/induzido quimicamente
16.
Arthritis Res Ther ; 22(1): 5, 2020 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-31915059

RESUMO

OBJECTIVE: To describe successful therapeutic strategies in statin-induced anti-HMGCR myopathy. METHODS: Retrospective data from a cohort of 55 patients with statin-induced anti-HMGCR myopathy, sequentially stratified by the presence of proximal weakness, early remission, and corticosteroid and IVIG use at treatment induction, were analyzed for optimal successful induction and maintenance of remission strategies. RESULTS: A total of 14 patients achieved remission with a corticosteroid-free induction strategy (25%). In 41 patients treated with corticosteroids, only 4 patients (10%) failed an initial triple steroid/IVIG/steroid-sparing immunosuppressant (SSI) induction strategy. Delay in treatment initiation was independently associated with lower odds of successful maintenance with immunosuppressant monotherapy (OR 0.92, 95% CI 0.85 to 0.97, P = 0.015). While 22 patients (40%) presented with normal strength, only 9 had normal strength at initiation of treatment. CONCLUSION: While corticosteroid-free treatment of anti-HMGCR myopathy is now a safe option in selected cases, initial triple steroid/IVIG/SSI was very efficacious in induction. Delays in treatment initiation and, as a corollary, delays in achieving remission decrease the odds of achieving successful maintenance with an SSI alone. Avoiding such delays, most notably in patients with normal strength, may reset the natural history of anti-HMGCR myopathy from a refractory entity to a treatable disease.


Assuntos
Doenças Autoimunes/induzido quimicamente , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Imunossupressores/uso terapêutico , Miosite/induzido quimicamente , Miosite/etiologia , Corticosteroides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes/tratamento farmacológico , Feminino , Humanos , Hidroximetilglutaril-CoA Redutases/imunologia , Imunoglobulinas Intravenosas/uso terapêutico , Quimioterapia de Indução/métodos , Quimioterapia de Manutenção/métodos , Masculino , Pessoa de Meia-Idade , Miosite/imunologia , Estudos Retrospectivos
17.
Curr Allergy Asthma Rep ; 20(1): 4, 2020 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-31993777

RESUMO

PURPOSE OF REVIEW: Progestogen hypersensitivity (PH) is a condition which typically occurs in women in childbearing years with a spectrum of symptoms ranging from urticaria with or without angioedema, dermatitis to systemic anaphylaxis. Herein, a clinical case of PH is presented followed by a discussion on the evaluation, diagnosis, and management of PH. RECENT FINDINGS: Progestogen hypersensitivity (a.k.a. "autoimmune progesterone dermatitis") symptoms are associated with exogenous progestin exposure (e.g., contraceptive medicines, in vitro fertilization therapy) or endogenous progesterone from progesterone surges during the luteal phase of the menstrual cycle and pregnancy. This condition can be difficult to recognize due to its heterogeneous clinical presentation. The mechanism of PH is believed to be primarily IgE-mediated; however, less commonly other immune responses may be involved. There is now a useful progesterone specific IgE immunoassay to assist in diagnosis and well-defined treatment algorithms that can be used to successfully manage PH. The epidemiology of PH is still poorly elucidated but is likely to be encountered by clinicians and especially allergists given the extensive use of oral contraceptives and increased use of supra-physiologic doses of progesterone required to support pregnancy in IVF. Including PH in the differential diagnosis of women presenting with cyclic hypersensitivity will accelerate diagnosis and successful management of this condition.


Assuntos
Anafilaxia/induzido quimicamente , Doenças Autoimunes/induzido quimicamente , Dispositivos Intrauterinos Medicados/efeitos adversos , Progesterona/efeitos adversos , Progestinas/efeitos adversos , Urticária/induzido quimicamente , Anafilaxia/diagnóstico , Anafilaxia/tratamento farmacológico , Antialérgicos/uso terapêutico , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/tratamento farmacológico , Dermatite/diagnóstico , Dermatite/tratamento farmacológico , Dessensibilização Imunológica , Remoção de Dispositivo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina E/sangue , Omalizumab/uso terapêutico , Urticária/diagnóstico , Urticária/tratamento farmacológico , Adulto Jovem
18.
J Neuroimmunol ; 340: 577146, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-31945592

RESUMO

Acquired Factor VIII inhibitor is a rare acquired clotting disorder which has been seen in the setting of particular medications, autoimmune disease, and malignancy. Reports of this disorder in patients receiving immunomodulatory therapies for multiple sclerosis are rare. We present a case of a 48 year-old woman with likely development of acquired Factor VIII inhibitor in the setting of interferon beta monotherapy for multiple sclerosis, and discuss the pathogenesis of this disorder which involves shifts in helper T cell populations and increased production of immunoglobulins.


Assuntos
Autoanticorpos/imunologia , Doenças Autoimunes/induzido quimicamente , Fator VIII/imunologia , Interferon beta-1a/efeitos adversos , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Autoantígenos/imunologia , Transtornos da Coagulação Sanguínea/induzido quimicamente , Feminino , Humanos , Pessoa de Meia-Idade
19.
J Clin Invest ; 130(1): 51-61, 2020 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-31895048

RESUMO

Immunotherapy has transformed the treatment landscape for a wide range of human cancers. Immune checkpoint inhibitors (ICIs), monoclonal antibodies that block the immune-regulatory "checkpoint" receptors CTLA-4, PD-1, or its ligand PD-L1, can produce durable responses in some patients. However, coupled with their success, these treatments commonly evoke a wide range of immune-related adverse events (irAEs) that can affect any organ system and can be treatment-limiting and life-threatening, such as diabetic ketoacidosis, which appears to be more frequent than initially described. The majority of irAEs from checkpoint blockade involve either barrier tissues (e.g., gastrointestinal mucosa or skin) or endocrine organs, although any organ system can be affected. Often, irAEs resemble spontaneous autoimmune diseases, such as inflammatory bowel disease, autoimmune thyroid disease, type 1 diabetes mellitus (T1D), and autoimmune pancreatitis. Yet whether similar molecular or pathologic mechanisms underlie these apparent autoimmune adverse events and classical autoimmune diseases is presently unknown. Interestingly, evidence links HLA alleles associated with high risk for autoimmune disease with ICI-induced T1D and colitis. Understanding the genetic risks and immunologic mechanisms driving ICI-mediated inflammatory toxicities may not only identify therapeutic targets useful for managing irAEs, but may also provide new insights into the pathoetiology and treatment of autoimmune diseases.


Assuntos
Anticorpos Monoclonais/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Doenças Autoimunes/induzido quimicamente , Imunoterapia/efeitos adversos , Neoplasias/tratamento farmacológico , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/fisiologia , Doenças do Sistema Endócrino/induzido quimicamente , Humanos , Doenças Inflamatórias Intestinais/induzido quimicamente , Neoplasias/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/fisiologia , Microambiente Tumoral/efeitos dos fármacos
20.
Rev Med Interne ; 41(5): 343-345, 2020 May.
Artigo em Francês | MEDLINE | ID: mdl-31818504

RESUMO

INTRODUCTION: Anakinra is an anti-IL-1RA targeting IL-1ß with a central role in the occurrence of auto-inflammatory diseases. Its use is not without risk. CASE REPORT: We report a case of late onset auto-inflammatory syndrome treated with anti-IL-1RA whose progression was marked by deep isolated thrombocytopenia, rapidly regressive after discontinuation of anakinra. CONCLUSION: Immuno-allergic thrombocytopenia to anakinra is a rare, but serious adverse event.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Proteína Antagonista do Receptor de Interleucina 1/efeitos adversos , Trombocitopenia/induzido quimicamente , Artrite Reumatoide/patologia , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/diagnóstico , Feminino , Humanos , Inflamação/induzido quimicamente , Inflamação/diagnóstico , Pessoa de Meia-Idade , Síndrome , Trombocitopenia/diagnóstico
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