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1.
Medicine (Baltimore) ; 98(41): e17348, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31593084

RESUMO

Immune checkpoint inhibitors (ICIs) like cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA4) and programmed death cell protein 1 (anti-PD1) have revolutionized cancer treatment. As ICI use becomes widespread, more immune-related adverse events (irAE's) are being reported. Our aim was to investigate the frequency and nature of new irAE's as well as report the frequency of flare-ups of pre-existing autoimmune conditions occurring after ICI therapy.We performed a retrospective chart review of all patients treated for cancer with anti-PD1 or anti-CTLA4 or combination therapy at our tertiary care center from January 2014 to April 2016. Demographic data, cancer type and stage, irAE's (new immune disorders and disease flares of pre-existing autoimmune disorders on ICI therapy), and drug treatment information were extracted.We identified 220 patients treated with ICI therapy during the study period out of which 27% (60/220) developed irAE's. 11% in anti-CTLA4 group and 16% among anti-PD1 treated patients developed irAE's. IrAE's resulted in discontinuation of cancer therapy in 28% of those who developed irAE's. 21.4% had a flare of their autoimmune disease but only 1 required discontinuation of immunotherapy.IrAE's are an important emerging clinical disease entity for specialists to be aware of. Our study shows that ICI's can be safely used in patients with pre-existing autoimmune conditions with close monitoring. However, there is still a large unmet need to have a better understanding of how to systematically evaluate and manage patients with irAE's as well as for identifying the predictors of irAE's.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Doenças do Sistema Imunitário/induzido quimicamente , Imunoterapia/efeitos adversos , Melanoma/tratamento farmacológico , Neoplasias/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/imunologia , Antígeno CTLA-4/antagonistas & inibidores , Feminino , Humanos , Doenças do Sistema Imunitário/imunologia , Masculino , Melanoma/imunologia , Pessoa de Meia-Idade , Neoplasias/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Estudos Retrospectivos
2.
Magy Onkol ; 63(3): 246-255, 2019 09 18.
Artigo em Húngaro | MEDLINE | ID: mdl-31533145

RESUMO

Therapy with immune checkpoint inhibitors (ICPis) has become widespread in medical oncology, becoming part of the routine treatment for various malignancies. These antibodies induce an anti-cancer immune activation by blocking the natural immunosuppression, which is supposed to protect the human body's healthy cells from destruction by the immune system, caused also by cancers, and as a result, allow the immune system to take part in destroying malignant cells. However, the immune activation created by these molecules is not selective against cancer tissues, therefore adverse events associated to these therapies are similar to the signs and symptoms of autoimmune diseases. Common adverse events affect the skin, liver, lungs, gastrointestinal and endocrine systems, less frequently the heart and the nervous system, occasionally causing life-threatening complications. Therapy of these adverse events requires rapid diagnosis and adequate treatment in the form of various immunosuppressants.


Assuntos
Antineoplásicos/efeitos adversos , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/prevenção & controle , Imunossupressão , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Doenças Autoimunes/imunologia , Humanos
3.
Intern Med ; 58(14): 2067-2072, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-30996157

RESUMO

We herein report a case of autoimmune pulmonary alveolar proteinosis (PAP) diagnosed after one-time exposure to silica powder. Owing to the misuse of a silica-containing fire extinguisher and the inhalation of large amounts of its powder, the patient experienced prolonged cough and visited our hospital. The findings of chest computed tomography and surgical lung biopsy specimens led to the diagnosis of PAP. Interestingly, the presence of anti-GM-CSF antibody was detected; therefore, both autoimmune characteristics and exposure to large amounts of silica may have caused the development of PAP in this patient. This case provides important insight into the mechanisms leading to the onset of PAP.


Assuntos
Doenças Autoimunes/fisiopatologia , Exposição Ambiental/efeitos adversos , Material Particulado/efeitos adversos , Proteinose Alveolar Pulmonar/induzido quimicamente , Proteinose Alveolar Pulmonar/diagnóstico , Dióxido de Silício/efeitos adversos , Administração por Inalação , Idoso , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/diagnóstico , Feminino , Sistemas de Combate a Incêndio , Humanos , Proteinose Alveolar Pulmonar/fisiopatologia
4.
Int J Immunopathol Pharmacol ; 33: 2058738419843690, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30968726

RESUMO

Alemtuzumab, an anti-CD52 monoclonal antibody, is effective in the treatment of relapsing-remitting multiple sclerosis (RRMS). Common adverse effects include the development of autoimmune diseases, and Graves' disease is one of the most frequent presentations. We report here a case of alemtuzumab-induced thyroid disease in a female patient who showed a phase of thyrotoxicosis with positive anti-thyroglobulin (anti-Tg) and anti-thyroid peroxidase (TPO) antibodies, but a negative TSH receptor antibody, spontaneously followed by hypothyroidism. The aim is to illustrate the clinical presentation, evaluation over time, and the possibility to consider a conservative management up to the spontaneous resolution of the thyrotoxicosis. All these are intended to emphasize the importance of pretreatment screening and follow-up in the management of treatment with alemtuzumab.


Assuntos
Alemtuzumab/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Doenças Autoimunes/induzido quimicamente , Hipotireoidismo/induzido quimicamente , Esclerose Múltipla/tratamento farmacológico , Adulto , Doenças Autoimunes/diagnóstico por imagem , Feminino , Humanos , Hipotireoidismo/diagnóstico por imagem , Esclerose Múltipla/diagnóstico por imagem
7.
Endocrinol. diabetes nutr. (Ed. impr.) ; 66(1): 26-34, ene. 2019. tab, graf
Artigo em Inglês | IBECS | ID: ibc-175790

RESUMO

Background: Nivolumab is an anti-cancer monoclonal antibody that inhibits PD1 and modulates T-cell response. It has been shown to significantly improve survival in several types of cancer, but clinical trials have also reported an increased risk of developing immune-related adverse events (IRAEs). Endocrine IRAEs may be particularly relevant. Objective: To comprehensively evaluate the clinical presentation of endocrine IRAEs in patients with lung cancer treated with nivolumab. Potential risk factors are analyzed, and strategies for IRAE management are proposed. Methods: Forty consecutive patients treated with nivolumab for advanced non-small cell lung cancer (NSCLC) were studied, paying particular attention to development of endocrine IRAEs (thyroid, hypophyseal, adrenal, or pancreatic) and clinical outcome. Results: Thyroid function changes were found in 9 patients (22.5%), of which six developed hypothyroidism and three had hyperthyroidism after a median of 3.8 and 2.3 cycles of nivolumab respectively. Only one patient had thyroid-related symptoms. Thyroid autoimmunity was negative in all cases. Hyperthyroid patients showed no uptake in iodine scintigraphy, and their hormone values returned to normal in less than six months. Nivolumab was discontinued for toxicity in one patient. One patient with hyperthyroidism also developed autoimmune diabetes, and one patient with hypothyroidism also had hypogonadism. After a median follow-up of 7.6 months, 25 patients (62.5%) showed response to nivolumab. Univariate and multivariate analyses showed no differences between patients who developed thyroid changes and those who did not. Conclusions: Thyroid changes after treatment with nivolumab are common and warrant active laboratory monitoring. The underlying mechanisms and their relevance deserve further research


Introducción: Nivolumab es un anticuerpo monoclonal que ejerce acción anti-tumoral mediante la inhibición de PD1 y modulación de la respuesta de las células T. Ha demostrado un aumento significativo en la supervivencia de distintos tipos de cáncer, pero también se ha reportado un incremento en el riesgo de desarrollar eventos adversos relacionados con la inmunidad (IRAEs). Los IRAEs endocrinos son particularmente relevantes. Objetivos: Evaluar de forma detallada la presentación clínica de los IRAEs endocrinos en pacientes con cáncer de pulmón refractario tratados con nivolumab. Se analizan potenciales factores de riesgo y se proponen estrategias para su manejo. Material y métodos: Se estudiaron 40 pacientes consecutivos con cáncer de pulmón de células no pequeñas (NSCLC) tratados con nivolumab. Se realizó el seguimiento prestando especial atención al desarrollo de los IRAEs endocrinos (tiroides, hipófisis, adrenal o páncreas) y su evolución clínica. Resultados: Se detectaron alteraciones de la función tiroidea en 9 casos (22,5%): 6 hipotiroidismo y 3 hipertiroidismo, tras una mediana de 3,8 y 2,3 ciclos de nivolumab, respectivamente. Solo un paciente desarrolló síntomas relacionados. La autoinmunidad tiroidea fue negativa en todos los casos. La gammagrafía fue negativa en todos los casos de hipertiroidismo y los valores hormonales volvieron a la normalidad en menos de 6 meses. Se suspendió nivolumab en un caso debido a toxicidad. Uno de los pacientes con hipertiroidismo también desarrolló diabetes autoinmune, y uno de los pacientes con hipotiroidismo también presentaba hipogonadismo. Tras una mediana de seguimiento de 7,6 meses, 25 pacientes (62,5%) presentaron respuesta favorable al nivolumab. El análisis uni y multivariante no mostró diferencias entre los pacientes que desarrollaron alteraciones tiroideas y los que no. Conclusiones: Las alteraciones tiroideas tras el tratamiento con nivolumab son frecuentes y requieren una vigilancia activa. Los mecanismos subyacentes y su relevancia aún no se conocen en profundidad


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Glândula Tireoide/fisiopatologia , Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Glândula Tireoide , Fatores de Risco , Doenças Autoimunes/induzido quimicamente , Carcinoma Pulmonar de Células não Pequenas/complicações , Tireoidite Autoimune
8.
Med Sci Monit ; 24: 9187-9195, 2018 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-30559337

RESUMO

BACKGROUND Recent data have demonstrated the potential immunosuppressive roles of interleukin-37 (IL-37) in several diseases, but whether it is involved in the pathogenesis of inflammatory myopathy has not been elucidated. MATERIAL AND METHODS An experimental autoimmune myositis (EAM) model was built by subcutaneous injections of pertussis toxin (PTX) and purified rabbit myosin (10mg/kg) emulsified with an equal volume of conventional complete Freund's adjuvant (CFA) in a Lewis model. Autoimmune myositis Lewis model rats were divided into 3 groups: group A rats (control group) were injected with CFA in saline weekly; group B (IL-37 group) rats were injected with saline with IL-37 and CFA in saline weekly; and group C (IL-37 + SIS3 group) rats were injected with IL-37, CFA, and SIS3. ELISA was also used to assess the expressions of TNF-α, IL-6, IL-1ß, TGF-ß1, and CK. HE staining was performed to assess pathological changes in lung and muscle tissues. RESULTS The expressions of TNF-α, IL-6, IL-1ß, TGF-ß1, and CK significantly increased in autoimmune myositis Lewis model rats. After IL-37 treatment, the expression of TNF-α, IL-6, IL-1ß, TGF-ß1, and CK was significantly reduced, as were the inflammatory responses of lung and muscle. However, SIS3 reduced the effects of IL-37 on the autoimmune myositis Lewis model rats. CONCLUSIONS These findings indicate that IL-37 protects against inflammatory response via regulating Smad3 in autoimmune myositis Lewis model rats.


Assuntos
Interleucina-1/farmacologia , Mielite/tratamento farmacológico , Mielite/imunologia , Animais , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/imunologia , Modelos Animais de Doenças , Feminino , Adjuvante de Freund/farmacologia , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-1/metabolismo , Interleucina-1beta/metabolismo , Mielite/induzido quimicamente , Toxina Pertussis , Engenharia de Proteínas/métodos , Ratos , Ratos Endogâmicos Lew , Fator de Crescimento Transformador beta1/biossíntese , Fator de Necrose Tumoral alfa/biossíntese
9.
J Clin Neuromuscul Dis ; 20(1): 28-34, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30124557

RESUMO

Immunomodulating drugs are widely used in autoimmune, transplant, and cancer patients. However, these drugs are associated with various autoimmune neuromuscular diseases such as demyelinating polyneuropathy, myasthenia gravis, and myositis. Early recognition of these complications and immediately terminating these drugs are very essential since some are life-threatening conditions. This review provides a general overview of drug-induced autoimmunity and autoimmune neuromuscular diseases associated with tumor necrosis factor alpha (TNF-α) antagonists, immune checkpoint inhibitors, and interferon (IFN) type 1 (IFN-ß and IFN-α).


Assuntos
Doenças Autoimunes/induzido quimicamente , Fatores Imunológicos/efeitos adversos , Doenças Neuromusculares/induzido quimicamente , Animais , Autoanticorpos/imunologia , Doenças Autoimunes/complicações , Humanos , Doenças Neuromusculares/complicações
10.
J Immunol Res ; 2018: 7645465, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29984259

RESUMO

Drug-induced hypersensitivity immune reactions are exaggerated immunoinflammatory responses to allergenic components of the medications that occur in genetically susceptible subjects. The type of hypersensitivity immune response generated, whether antibody mediated or T cell mediated, or an immune complex reaction is determined by multiple factors, including the molecular characteristics of the allergen, the route of administration of the medication, the manner of presentation of the allergen by antigen-presenting cells to naïve T cells, the repertoire of the T cell receptors, and the cytokine profile within the microenvironment. This review deals with the clinical and histopathological aspects of adverse immunologically mediated oral mucosal reactions to systemic medication. We elaborate on diseases showing features of lichenoid tissue reaction/interface dermatitis-stomatitis, autoimmune vesiculobullous oral lesions, and immunoglobulin E- (IgE-) and immune complex-mediated oral reactions to drugs.


Assuntos
Erupção por Droga/imunologia , Hipersensibilidade a Drogas/imunologia , Doenças da Boca/induzido quimicamente , Doenças da Boca/imunologia , Mucosa Bucal/imunologia , Estomatite/induzido quimicamente , Alérgenos/imunologia , Anafilaxia/induzido quimicamente , Anafilaxia/imunologia , Complexo Antígeno-Anticorpo , Reações Antígeno-Anticorpo/efeitos dos fármacos , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/imunologia , Eritema Multiforme/induzido quimicamente , Eritema Multiforme/imunologia , Humanos , Imunoglobulina E/imunologia , Líquen Plano , Erupções Liquenoides/induzido quimicamente , Mucosa Bucal/efeitos dos fármacos , Dermatopatias Vesiculobolhosas/induzido quimicamente , Dermatopatias Vesiculobolhosas/imunologia
11.
Diabetes ; 67(8): 1471-1480, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29937434

RESUMO

Insulin-dependent diabetes may occur in patients with cancers who are treated with checkpoint inhibitors (CPIs). We reviewed cases occurring over a 6-year period at two academic institutions and identified 27 patients in whom this developed, or an incidence of 0.9%. The patients had a variety of solid-organ cancers, but all had received either anti-PD-1 or anti-PD-L1 antibodies. Diabetes presented with ketoacidosis in 59%, and 42% had evidence of pancreatitis in the peridiagnosis period. Forty percent had at least one positive autoantibody and 21% had two or more. There was a predominance of HLA-DR4, which was present in 76% of patients. Other immune adverse events were seen in 70%, and endocrine adverse events in 44%. We conclude that autoimmune, insulin-dependent diabetes occurs in close to 1% of patients treated with anti-PD-1 or -PD-L1 CPIs. This syndrome has similarities and differences compared with classic type 1 diabetes. The dominance of HLA-DR4 suggests an opportunity to identify those at highest risk of these complications and to discover insights into the mechanisms of this adverse event.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Doenças Autoimunes/induzido quimicamente , Antígeno B7-H1/antagonistas & inibidores , Diabetes Mellitus Tipo 1/etiologia , Modelos Imunológicos , Pancreatite/induzido quimicamente , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Animais , Antineoplásicos Imunológicos/uso terapêutico , Doenças Autoimunes/imunologia , Doenças Autoimunes/metabolismo , Doenças Autoimunes/fisiopatologia , Antígeno B7-H1/metabolismo , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/genética , Predisposição Genética para Doença , Genótipo , Antígeno HLA-DR4/sangue , Antígeno HLA-DR4/genética , Antígeno HLA-DR4/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/metabolismo , Insulina/uso terapêutico , Isoanticorpos/análise , Cetose/etiologia , Cetose/prevenção & controle , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Pâncreas/efeitos dos fármacos , Pâncreas/imunologia , Pâncreas/metabolismo , Pancreatite/imunologia , Pancreatite/metabolismo , Pancreatite/fisiopatologia , Receptor de Morte Celular Programada 1/metabolismo
12.
BMJ Case Rep ; 20182018 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-29691272

RESUMO

Immune-mediated necrotising myopathy (IMNM) is a type of inflammatory myopathy characterised by acute or subacute severe proximal muscle weakness, significantly elevated creatine kinase levels, and prominent myofibre necrosis and regeneration with little or no inflammation. A subtype of IMNM identified by anti-HMG-CoA reductase (HMGCR)antibodies has been shown to be associated with statin exposure. Treatment of IMNM consists of immunosuppression with steroids, steroid-sparing agents, intravenous immune globulin and/or biologics. We present here a case of anti-HMCGR-associated IMNM and review the pathophysiology, diagnosis and treatment to increase physician awareness of this rare and debilitating condition.


Assuntos
Doenças Autoimunes/patologia , Creatina Quinase/sangue , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Doenças Musculares/patologia , Miosite/patologia , Necrose/patologia , Administração Intravenosa , Idoso , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/tratamento farmacológico , Biópsia , Diagnóstico Diferencial , Inibidores Enzimáticos/uso terapêutico , Glucocorticoides/uso terapêutico , Humanos , Hidroximetilglutaril-CoA Redutases/imunologia , Imunoglobulinas Intravenosas/administração & dosagem , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Debilidade Muscular/patologia , Doenças Musculares/imunologia , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/uso terapêutico , Miosite/induzido quimicamente , Miosite/tratamento farmacológico , Resultado do Tratamento
13.
Clin Rheumatol ; 37(6): 1441-1448, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29619588

RESUMO

Autoimmune/inflammatory syndrome induced by adjuvant (ASIA) includes the following conditions: siliconosis, Gulf War syndrome, macrophagic myofasciitis syndrome, and post-vaccination phenomena. Afterward, other syndromes have been recognized, such as in ASIA by mineral oil (ASIA-MO). These conditions are triggered by adjuvants and they are the result of the interplay of genetic and environmental factors. ASIA-MO is defined as the infiltration of oily type modeling substances for cosmetic purposes. It has been reported in many countries and used surreptitiously. Pathogenesis of ASIA-MO is not clear, but is characterized by chronic granulomatous inflammation, like the pristane model in mice, with increase of proinflammatory cytokines: type I interferons (IFNα and IFNß), systemic lupus erythematosus (SLE), and erosive arthritis. In humans, an increase of interleukin 1 (IL-1) has been found. Clinical spectrum of ASIA-MO is heterogeneous, varying from mild to severe and being local and systemic. The systemic manifestations can be non-specific and specific, meeting criteria for any autoimmune disease (AID), i.e., SLE, rheumatoid arthritis, and systemic sclerosis, among others. The areas of the body where the mineral oil is mostly applied include the following: buttocks (38-72%), breasts (12-16%), lower extremities (18-22%), and face (6-10%). The penis augmentation is also common. Treatment is focused on local and systemic manifestations and requires medical and surgical management representing a challenge for the physician.


Assuntos
Doenças Autoimunes/induzido quimicamente , Técnicas Cosméticas/efeitos adversos , Óleo Mineral/efeitos adversos , Animais , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/terapia , Humanos
14.
Autoimmun Rev ; 17(6): 610-616, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29631064

RESUMO

The discovery and approved treatment with immune checkpoint inhibitors (ICIs) for a variety of cancers has changed dramatically the morbidity and mortality rates for these patients. Despite the obvious benefits, their use is associated with unique immune-related adverse effects (irAEs), including autoimmune conditions such as: inflammatory arthritis, myositis, vasculitis and Sicca syndrome. The appearance of ICIs-induced autoimmune irAE requires from oncologists and rheumatologists a different approach to the identification and treatment of these conditions, which may differ from the classic and traditional approach to rheumatologic diseases. It should be taken into consideration that ICIs therapy in patients with preexisting autoimmunity could be possible, but with a cost of causing disease exacerbation. In this extensive review, we present the autoimmune irAEs, mostly as phenomena, but also as classic autoimmune diseases as well as therapeutic options for the side effects.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Doenças Autoimunes/induzido quimicamente , Autoimunidade/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Anticorpos Monoclonais/efeitos adversos , Antineoplásicos/efeitos adversos , Artrite/induzido quimicamente , Artrite/imunologia , Doenças Autoimunes/imunologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/imunologia , Progressão da Doença , Humanos , Ipilimumab/efeitos adversos , Ipilimumab/uso terapêutico , Miosite/induzido quimicamente , Miosite/imunologia , Síndrome de Sjogren/induzido quimicamente , Síndrome de Sjogren/imunologia , Vasculite/induzido quimicamente , Vasculite/imunologia
15.
Discov Med ; 25(136): 75-83, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29579414

RESUMO

The inflammatory myopathies, which include dermatomyositis, polymyositis, and the immune-mediated necrotizing myopathies, are a heterogeneous group of autoimmune diseases that manifest with muscle, skin, or lung damage. Collectively, these autoimmune diseases result from loss of tolerance to a select group of self-antigens, although the precise mechanism through which this occurs is not known. Infection, malignancy, and certain medications including statins and the immune checkpoint inhibitors used in cancer therapy have been identified as potential immunologic triggers of the inflammatory myopathies. Some of these triggers are classically associated with specific myositis-specific autoantibodies (MSAs). The strong association between certain triggers and MSAs provides insights into how an immunologic event can lead to loss of tolerance to specific self-antigens, resulting in autoimmune disease. In this review, we discuss the proposed triggers of the inflammatory myopathies and their associations with MSAs, and provide insights into how these triggers may result in the inflammatory myopathies.


Assuntos
Antineoplásicos/efeitos adversos , Doenças Autoimunes , Dermatomiosite , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Polimiosite , Animais , Antineoplásicos/uso terapêutico , Autoanticorpos/imunologia , Autoantígenos/imunologia , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Dermatomiosite/induzido quimicamente , Dermatomiosite/imunologia , Dermatomiosite/patologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pulmão/imunologia , Pulmão/patologia , Músculos/imunologia , Músculos/patologia , Polimiosite/induzido quimicamente , Polimiosite/imunologia , Polimiosite/patologia , Pele/imunologia , Pele/patologia
17.
Biomed Res Int ; 2018: 3140983, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29546055

RESUMO

Psoriasis is a chronic inflammatory disease of the skin affecting approximately 2% of the world's population. Systemic treatments, including methotrexate and cyclosporin, are associated with potential hepatotoxicity, due to either direct liver damage or immunosuppression or both immunomediated and a direct liver injury; therefore, treatment of patients with psoriasis poses a therapeutic challenge. The aim of this minireview is to help clinicians in the management of psoriatic patients who develop signs of liver dysfunction. To find relevant articles, a comprehensive search was performed on PubMed, EMBASE, and Cochrane with appropriate combinations of the following keywords being considered: viral hepatitis, nonalcoholic fatty liver disease, psoriasis, hepatotoxicity, drug toxicity, cholestasis, and autoimmune liver diseases.


Assuntos
Doenças Autoimunes/epidemiologia , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Inflamação/epidemiologia , Psoríase/tratamento farmacológico , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/patologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Ciclosporina/efeitos adversos , Ciclosporina/uso terapêutico , Humanos , Inflamação/induzido quimicamente , Fígado/efeitos dos fármacos , Fígado/patologia , Hepatopatias/epidemiologia , Hepatopatias/patologia , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Psoríase/complicações , Psoríase/epidemiologia , Psoríase/patologia
19.
BMJ Case Rep ; 20182018 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-29437773

RESUMO

A 43-year-old woman with a history of recently diagnosed metastatic melanoma was commenced on systemic therapy with nivolumab, an anti-programmed cell death-1 monoclonal antibody and one of an increasing group of the so-called 'immune checkpoint inhibitors'. She experienced a dramatic complete response within 6 months of initiation. However, in addition to developing incident autoimmune hypothyroidism, she also developed progressive fatigue, proximal weakness, myalgia and dysphagia. Initial investigations with blood tests, electrophysiology and a muscle biopsy were non-specific or normal. Subsequent examination revealed 'woody' thickening of the subcutaneous tissues of the forearms, thighs and calves consistent with fasciitis. MRI and a full-thickness skin-muscle biopsy were ultimately diagnostic of a likely iatrogenic autoimmune myofasciitis. The clinical manifestations only responded partly to prednisolone 30 mg orally and treatment was escalated to include intravenous immunoglobulin. At 3 months, this has only resulted in a modest incremental improvement.


Assuntos
Anticorpos Monoclonais/efeitos adversos , Antineoplásicos/efeitos adversos , Doenças Autoimunes/induzido quimicamente , Antígeno B7-H1/efeitos adversos , Fasciite/induzido quimicamente , Melanoma/tratamento farmacológico , Anticorpos Monoclonais/administração & dosagem , Antineoplásicos/administração & dosagem , Doenças Autoimunes/diagnóstico por imagem , Doenças Autoimunes/tratamento farmacológico , Biópsia , Fasciite/diagnóstico por imagem , Fasciite/tratamento farmacológico , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imunoterapia/efeitos adversos , Imagem por Ressonância Magnética , Melanoma/patologia , Pessoa de Meia-Idade , Nivolumabe
20.
Gynecol Oncol ; 148(3): 591-600, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29395304

RESUMO

As precision medicine has become a focus in oncology in recent years, many targeted and biologic agents are being used along with or in place of traditional cytotoxic chemotherapy. As these drugs have been developed and some have received FDA approval, we have gained substantial data about the adverse event profiles. However, the management and approach to the toxicities incurred and subsequent complications are often not well understood, especially for physicians who have a varied clinical practice. The purpose of this review is to provide an overview of the frequency and types of adverse events and appropriate management steps when prescribing modern targeted therapies for gynecologic cancers in the classes of anti-angiogenic agents, poly-ADP-ribose polymerase (PARP) inhibitors, and immunotherapy drugs.


Assuntos
Inibidores da Angiogênese/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Neoplasias dos Genitais Femininos/tratamento farmacológico , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Anemia/induzido quimicamente , Anemia/terapia , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/terapia , Bevacizumab/efeitos adversos , Diarreia/induzido quimicamente , Diarreia/terapia , Epistaxe/induzido quimicamente , Epistaxe/terapia , Fadiga/induzido quimicamente , Fadiga/terapia , Feminino , Cefaleia/induzido quimicamente , Cefaleia/terapia , Hemorragia/induzido quimicamente , Hemorragia/terapia , Humanos , Hipertensão/induzido quimicamente , Hipertensão/terapia , Perfuração Intestinal/induzido quimicamente , Perfuração Intestinal/terapia , Terapia de Alvo Molecular , Náusea/induzido quimicamente , Náusea/terapia , Neutropenia/induzido quimicamente , Neutropenia/terapia , Medicina de Precisão , Proteinúria/induzido quimicamente , Proteinúria/terapia , Pirimidinas/efeitos adversos , Medição de Risco , Sulfonamidas/efeitos adversos , Vômito/induzido quimicamente , Vômito/terapia , Desequilíbrio Hidroeletrolítico/induzido quimicamente , Desequilíbrio Hidroeletrolítico/terapia
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