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Rev. chil. endocrinol. diabetes ; 16(4): 121-123, 2023.
Article in Spanish | LILACS | ID: biblio-1512165


Los inhibidores de checkpoint (ICP) son anticuerpos usados en inmunoterapia contra el cáncer. Uno de sus blancos de acción es el receptor de muerte celular programada-1 (PD-1), el cual es importante para mantener la tolerancia inmunitaria. Sin embargo, este mecanismo se asocia a riesgo de eventos adversos relacionados a la inmunidad que pueden afectar a múltiples órganos incluyendo el sistema endocrino. Se describe el caso inhabitual de un paciente que a los 18 meses de terapia con ICP debutó con cetoacidosis diabética (CAD).

Immune checkpoint inhibitors consist in antibodies used in immunotherapy against cancer. One of their targets is the programmed cell death-1 (PD-1) receptor, which is important in maintaining self-tolerance. However, this mechanism is associated with a risk for immune-related adverse events potentially affecting multiple organs, including the endocrine system. We describe the unusual case of a patient who, after 18 months of treatment with an immune checkpoint inhibitor, debuted with diabetic ketoacidosis

Humans , Male , Middle Aged , Diabetic Ketoacidosis/chemically induced , Antibodies, Monoclonal, Humanized/adverse effects , Immune Checkpoint Inhibitors/adverse effects , Skin Neoplasms/drug therapy , Diabetic Ketoacidosis/immunology , Diabetes Mellitus/chemically induced , Cell Cycle Checkpoints , Antineoplastic Agents, Immunological/adverse effects , Immunotherapy/adverse effects , Melanoma/drug therapy
Article in Portuguese | LILACS, CONASS, ColecionaSUS, SES-GO | ID: biblio-1451819


Tecnologia: Dupilumabe e upadacitinibe. Comparadores: Azatioprina, metotrexato, ciclosporina, micofenolato de mofetila. Indicação: Tratamento de dermatite atópica severa em pacientes adultos. Pergunta: Dupilumabe e upadacitinibe são mais eficazes e tão seguros quanto ciclosporina ou outros agentes imunossupressores para obter os desfechos de saúde no tratamento sistêmico de dermatite atópica moderada a grave refratária à terapia atópica? Métodos: Levantamento bibliográfico foi realizado na base de dados PUBMED e Cochrane Library, seguindo estratégias de buscas predefinidas. Foi feita avaliação da qualidade metodológica das revisões sistemáticas com a ferramenta AMSTAR2 (Assessing the Methodological Quality of Systematic Reviews Version 2). Resultados: Foram selecionados três estudos que atenderam aos critérios de inclusão. Conclusão: Dupilumabe, upadacitinibe, ciclosporina e azatioprina são mais eficazes que placebo nos desfechos de eficácia (reduzir sinais clínicos em escalas, reduzir sintomas em escalas) para tratamento da dermatite atópica moderada a grave refratária à terapia tópica, mas esses medicamentos não diferem entre si. Dupilumabe, upadacitinibe, ciclosporina e azatioprina são bem tolerados e seguros

Technology: Dupilumab, upadacitinibe. Comparators: Azathioprine, methotrexate, cyclosporine, mycophenolate mofetil. Indication: Treatment of severe atopic dermatitis in adult patients. Question: Are dupilumab and upadacitinib more effective and as safe as cyclosporine or other immunosuppressive agents for achieving health outcomes in the systemic treatment of moderate to severe atopic dermatitis refractory to atopic therapy? Methods: A bibliographic survey was done in the PUBMED e Cochrane Library databases, following predefined search strategies. The methodological quality of systematic reviews was evaluated using the AMSTAR-2 tool (Assessing the Methodological Quality of Systematic Reviews Version 2). Results: Three studies that met the inclusion criteria were selected. Conclusion: Dupilumab, upadacitinib, cyclosporine, and azathioprine are more effective than placebo on efficacy endpoints (reduce clinical signs on scales, reduce symptoms on scales) for treating moderate to severe atopic dermatitis refractory to topical therapy, but these drugs do not differ from each other. Dupilumab, upadacitinib, cyclosporine, and azathioprine are well tolerated and safe

Humans , Male , Female , Dermatitis, Atopic/drug therapy , Immunologic Factors/therapeutic use , Immunosuppressive Agents/therapeutic use , Azathioprine/therapeutic use , Methotrexate/therapeutic use , Cyclosporine/therapeutic use , Antibodies, Monoclonal, Humanized , Janus Kinase Inhibitors
Chinese Medical Sciences Journal ; (4): 159-162, 2023.
Article in English | WPRIM | ID: wpr-981598


Food-dependent, exercise-induced anaphylaxis (FDEIA) is a potentially life-threatening disorder that often occurs with exercise, and patients typically have eaten a specific food within hours before disease onset. This disease is exceedingly rare, with a prevalence of 0.02%. No well-recognized prevention or treatment strategy has been available for FDEIA except avoiding triggers strictly. Here we report an 11-year-old boy with a history of recurrent anaphylaxis of unknown etiology more than 10 times within two years. As the anaphylactic symptoms had not been controlled after traditional treatments, the patient was given subcutaneous injection of dupilumab seven times within 33 weeks. During dupilumab treatments, the patient was exposed to culprit mushrooms plus exercises at least twice a month but without notable anaphylaxis. Thus, Dupilumab may improve the allergic reactions in FDEIA patients.

Male , Humans , Child , Anaphylaxis/etiology , Food Hypersensitivity/diagnosis , Exercise-Induced Allergies , Antibodies, Monoclonal, Humanized/therapeutic use
Chinese Journal of Oncology ; (12): 358-367, 2023.
Article in Chinese | WPRIM | ID: wpr-984730


Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.

Humans , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , Treatment Outcome
Rev. chil. obstet. ginecol. (En línea) ; 87(5): 350-355, oct. 2022.
Article in English | LILACS | ID: biblio-1423738


Atypical hemolytic-uremic syndrome (aHUS) is a rare entity characterized by the association of acute kidney failure, thrombocytopenia and microangiopathic hemolytic anemia due to the dysregulation of the alternative pathway of the complement system. It is included within the thrombotic microangiopathies. The following aHUS was developed in the immediate puerperium in the context of severe preeclampsia. The patient was a primiparous woman of 30+1 weeks who required hospitalization for anticonvulsant and hypotensive treatment, and who underwent an emergency cesarean section due to a pathological cardiotocographic pattern. 36 hours after delivery, the patient presented with sudden dyspnea and cognitive deterioration, progressing in a few hours to renal and multiorgan failure. Blood test showed severe anemia, thrombopenia and hypertransaminemia. In view of the fast evolution and severity, it was decided to treat with Eculizumab, although the scientific evidence was very poor. Aside from the supportive treatment performed in the Intensive Care Unit, the patient was successfully treated with Eculizumab, with favorable evolution over the following months and restoration of kidney function, although need for chronic hypotensive treatment remained.

El síndrome hemolítico-urémico atípico (SHUa) es una entidad rara caracterizada por la asociación de insuficiencia renal aguda, trombocitopenia y anemia hemolítica microangiopática debido a la desregulación de la vía alternativa del sistema del complemento. Se incluye dentro de las microangiopatías trombóticas. Se presenta un SHUa que se desarrolló en el puerperio inmediato en el contexto de una preeclampsia grave. La paciente era una primípara de 30+1 semanas que requirió hospitalización para tratamiento anticonvulsivo e hipotensor, y a la que se le practicó una cesárea de urgencia por un patrón cardiotocográfico patológico. A las 36 horas del parto, la paciente presentó una disnea súbita y un deterioro cognitivo progresivo, que evolucionó en pocas horas a un fallo renal agudo y multiorgánico. La analítica mostró anemia severa, trombopenia e hipertransaminemia. Ante la rápida evolución y gravedad, se decidió tratar con Eculizumab, aunque la evidencia científica era escasa. Aparte del tratamiento de soporte realizado en la Unidad de Cuidados Intensivos, la paciente fue tratada con éxito con Eculizumab, con evolución favorable en los meses siguientes y restablecimiento de la función renal, aunque se mantuvo la necesidad de tratamiento hipotensor crónico.

Humans , Female , Young Adult , Antibodies, Monoclonal, Humanized/therapeutic use , Atypical Hemolytic Uremic Syndrome/drug therapy , Immunologic Factors/therapeutic use , Pre-Eclampsia , Pregnancy Complications , Cesarean Section , Postpartum Period , Atypical Hemolytic Uremic Syndrome/diagnosis
Rev. méd. hondur ; 90(1): 28-35, ene.-jun. 2022. tab.
Article in Spanish | LILACS, BIMENA | ID: biblio-1393003


Antecedentes: La pandemia de COVID-19 ha provocado una crisis de salud pública mundial, creando incertidumbre sobre su tratamiento. El Tocilizumab (TCZ), un anticuerpo monoclonal humanizado que actúa como antagonista del receptor de Interleucina 6 (IL-6), ha sido utilizado en enfermedades inmunológicas y en pacientes críticos por COVID-19. Objetivo: Describir el uso de TCZ en pacientes adultos hospitalizados por COVID-19 en Hospital María Especialidades Pediátricas (HMEP), agosto 2020-marzo 2021. Métodos: Estudio descriptivo, retrospectivo. Fuente de datos: expedientes clínicos. Criterios de inclusión: Adulto mayor de 18 años, manejo hospitalario por COVID-19, con TCZ y expediente clínico completo. Criterios de exclusión: Haber recibido TCZ en otro hospital. Se utilizó estadística descriptiva y se realizó análisis de sobrevida de Kaplan & Meier para comparar las probabilidades de sobrevida según edad, con un nivel se significancia p<0.05. Resultados: Se analizaron 104 expedientes clínicos. La mediana de edad de los pacientes fue 57 años (RI=44-67), la edad fue mayor en los pacientes fallecidos; 60% (62/104) del sexo masculino. Los pacientes mostraron mejoría en parámetros clínicos y laboratoriales, como descensos en frecuencia respiratoria y frecuencia cardíaca, aumento de linfocitos y descenso de Proteína C Reactiva (PCR). El análisis de sobrevida de Kaplan & Meier mostró que la probabilidad de vivir en estos pacientes disminuye conforme aumenta la edad. Discusión: Los resultados de este estudio coinciden con los encontrados a nivel internacional, avalando el uso de TCZ en pacientes críticos por COVID-19...(AU)

Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , Retrospective Studies , Age Distribution , COVID-19/mortality , Honduras/epidemiology , Hospitals, Public
Arq. Asma, Alerg. Imunol ; 6(2): 170-196, abr.jun.2022. ilus
Article in English, Portuguese | LILACS | ID: biblio-1400199


O tratamento do angioedema hereditário tem início com a educação dos pacientes e familiares sobre a doença, pois é fundamental o conhecimento da imprevisibilidade das crises, assim como os seus fatores desencadeantes. O tratamento medicamentoso se divide em terapia das crises e profilaxia das manifestações clínicas. As crises devem ser tratadas o mais precocemente possível com o uso do antagonista do receptor de bradicinina, o icatibanto ou o concentrado de C1-inibidor. É necessário estabeler um plano de ação em caso de crises para todos os pacientes. A profilaxia de longo prazo dos sintomas deve ser realizada preferencialmente com medicamentos de primeira linha, como concentrado do C1-inibidor ou o anticorpo monoclonal anti-calicreína, lanadelumabe. Como segunda linha de tratamento temos os andrógenos atenuados. Na profilaxia de curto prazo, antes de procedimentos que podem desencadear crises, o uso do concentrado de C1-inibidor é preconizado. Existem algumas restrições para uso desses tratamentos em crianças e gestantes que devem ser consideradas. Novos medicamentos baseados nos avanços do conhecimento da fisiopatologia do angioedema hereditário estão em desenvolvimento, devendo melhorar a qualidade de vida dos pacientes. O uso de ferramentas padronizadas para monitorização da qualidade de vida, do controle e da atividade da doença são fundamentais no acompanhamento destes pacientes. A criação de associações de pacientes e familiares de pacientes com angioedema hereditário tem desempenhado um papel muito importante no cuidado destes pacientes no nosso país.

The treatment of hereditary angioedema begins with the education of patients and their families about the disease, as it is essential to know the unpredictability of attacks as well as their triggering factors. Drug treatment is divided into attack therapy and prophylaxis of clinical manifestations. Attacks should be treated as early as possible with the bradykinin receptor antagonist icatibant or C1-inhibitor concentrate. An action plan needs to be established for all patients with attacks. Long-term prophylaxis of symptoms should preferably be performed with first-line drugs such as C1-inhibitor concentrate or the anti-kallikrein monoclonal antibody lanadelumab. Attenuated androgens are the second line of treatment. In short-term prophylaxis, before procedures that can trigger attacks, the use of C1-inhibitor concentrate is recommended. There are some restrictions for the use of these treatments in children and pregnant women that should be considered. New drugs based on advances in knowledge of the pathophysiology of hereditary angioedema are under development and are expected to improve patient quality of life. The use of standardized tools for monitoring quality of life and controlling disease activity is essential in the follow-up of these patients. The creation of associations of patients and families of patients with hereditary angioedema has played a very important role in the care of these patients in Brazil.

Humans , Drug Therapy , Angioedemas, Hereditary , Antibodies, Monoclonal, Humanized , Bradykinin Receptor Antagonists , Patients , Quality of Life , Therapeutics , Bradykinin , Pharmaceutical Preparations , Kallikreins , Reference Drugs
Arq. Asma, Alerg. Imunol ; 6(2): 295-299, abr.jun.2022. ilus
Article in English, Portuguese | LILACS | ID: biblio-1400226


O uso do anticorpo monoclonal dupilumabe em adultos tem possibilitado o controle da inflamação crônica, reduzindo significativamente o tamanho e a recorrência de novos pólipos, melhorando os sintomas nasais e, consequentemente, a qualidade de vida desses indivíduos. Relatamos o caso de uma adolescente que evidencia a eficácia de dupilumabe no tratamento da rinossinusite crônica com pólipo nasal.

The use of the monoclonal antibody dupilumab in adults has allowed the control of chronic inflammation, significantly reducing the size and recurrence of new polyps, improving nasal symptoms, and, consequently, quality of life. We report a successful case of dupilumab use in an adolescent for the treatment of chronic rhinosinusitis with nasal polyps.

Humans , Female , Adolescent , Sinusitis , Rhinitis , Nasal Polyps , Antibodies, Monoclonal, Humanized , Quality of Life , Recurrence , Signs and Symptoms , Therapeutics , Airway Obstruction
Rev. Méd. Inst. Mex. Seguro Soc ; 60(2): 201-210, abr. 2022. ilus, tab
Article in Spanish | LILACS | ID: biblio-1367344


El manejo del asma grave descontrolada con biológicos es un área de extrema dificultad, dada la escasez de información respecto a los criterios de inicio de los mismos, las variables a evaluar para determinar la eficacia y seguridad de su manejo, los puntos de corte para determinar el momento oportuno para cambiar o agregar otro biológico y el proceso para disminuir o retirar los esteroides. Esta revisión incorpora la información más reciente y realiza una propuesta con base en ella.

The management of severe uncontrolled asthma with biologics is an area of extreme difficulty given the scarcity of information regarding their starting criteria, the variables to be evaluated to determine the efficacy and safety of their management, the cut-off points to determine the timing to change or add another biological and the process to decrease or withdraw steroids. This review incorporates the latest information and makes a proposal based on it

Humans , Male , Female , Asthma/drug therapy , Biological Therapy , Asthma/immunology , Biomarkers/blood , Follow-Up Studies , Treatment Outcome , Adrenal Cortex Hormones/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use
Medwave ; 22(2): e002118, mar.2022. tab
Article in English, Spanish | LILACS | ID: biblio-1366391


Contexto La hemofilia es un trastorno hemorrágico de la coagulación que ocurre en uno de cada 5000 nacimientos masculinos. Los pacientes con hemofilia A grave no tratados tienen complicaciones hemorrágicas, incluyendo sangrados articulares y menor sobrevida. El emicizumab es un anticuerpo monoclonal aprobado por los Estados Unidos para la profilaxis rutinaria de pacientes pediátricos y adultos con hemofilia A grave con inhibidores del factor VIII de coagulación. Objetivos Realizar un estudio de costo-efectividad de la profilaxis con emicizumab para niños y adultos con hemofilia A grave, en comparación con el actual manejo de esos pacientes en el Ministerio de Salud y el Seguro Social de Salud de Perú. Metodología Se modeló la transición del paciente entre estados médicos con la metodología de Markov y se estimó a lo largo de su vida costos y efectos incrementales de emicizumab comparados con el actual manejo. Se estimó el impacto presupuestario de emicizumab proyectando costos netos anuales y su valor presente a cinco años. Resultados Emicizumab generaría ahorros en el Ministerio de Salud entre 14,6 y 16,0 por niño y 11,8 por adulto, en US$ millones actuales, y en el Seguro Social de Salud de 12,8 a 14,9 por niño y 40,1 por adulto. Además, se generan ganancias en efectividad, medidas en años de vida ajustados por calidad, de 0,36 por niño y 0,56 por adulto y de 0,25 por niño y 0,36 por adulto en esas respectivas instituciones. El impacto presupuestario sería un ahorro anual neto, en US$ millones, de 12,8 y 15,0 en esas entidades. Conclusión El actual manejo de la enfermedad es muy costoso y con resultados de salud inferiores a los posibles con emicizumab. Este fármaco produciría grandes ahorros y mejor salud. Ambas entidades debieran implementar protocolos para la profilaxis y tratamiento de la hemofilia y financiarla con presupuesto propio.

Settings Hemophilia is a coagulation disorder that occurs in one in 5000 male births. Patients with untreated severe hemophilia A have hemorrhagic complications, including joint bleeds and decreased survival. Emicizumab is a monoclonal antibody approved by the United States for routine prophylaxis of pediatric and adult patients with severe hemophilia A with factor VIII inhibitors. Objectives To perform a cost-effectiveness study of emicizumab prophylaxis for children and adults with severe hemophilia A compared with the current disease management in the Peruvian Ministry of Health and Social Security Health Insurance. Methods The patient transition between medical states was modeled with Markov methodology, and the lifetime costs and incremental effects of emicizumab compared to current management were estimated. The budgetary impact of emicizumab was estimated by projecting annual net costs and its five-year present value. Results In the Ministry of Health, emicizumab would generate savings between 14.6 and 16.0 per child and 11.8 per adult, in current US$ million. Social Security Health Insurance savings would be 12.8 to 14.9 per child and 40.1 per adult. In addition, this strategy would generate effectiveness gains, measured in quality-adjusted life-years, of 0.36 per child and 0.56 per adult and 0.25 per child, and 0.36 per adult in those respective institutions. The budgetary impact would be a net annual saving of 12.8 and 15.0 US$ million in those entities. Conclusions The current management of hemophilia A is very costly and has health outcomes inferior to those possible with emicizumab. This drug would produce significant savings and better patient health. The Ministry of Health and Social Health Insurance should implement hemophilia prophylaxis and treatment protocols and finance this drug.

Humans , Male , Child , Adult , Hemophilia A/complications , Hemophilia A/drug therapy , Peru , Factor VIII/therapeutic use , Cost-Benefit Analysis , Antibodies, Bispecific , Antibodies, Monoclonal, Humanized , Hemorrhage/etiology
Arq. Asma, Alerg. Imunol ; 6(1): 4-48, jan.mar.2022. ilus
Article in English, Portuguese | LILACS | ID: biblio-1400091


A alergia ocular, também conhecida como conjuntivite alérgica (CA), é uma reação de hipersensibilidade mediada por imunoglobulina E (IgE) do olho desencadeada por aeroalérgenos, principalmente ácaros da poeira doméstica e pólen de gramíneas. Os sintomas geralmente consistem em prurido ocular ou periocular, lacrimejamento e olhos vermelhos que podem estar presentes durante todo o ano ou sazonalmente. A alergia ocular tem frequência elevada, é subdiagnosticada e pode ser debilitante para o paciente. É potencialmente danosa para a visão, nos casos em que ocasiona cicatrização corneana grave, e na maioria dos pacientes associa-se a outros quadros alérgicos, principalmente rinite, asma e dermatite atópica. É classificada em conjuntivite alérgica perene, conjuntivite alérgica sazonal, ceratoconjuntivite atópica e ceratoconjuntivite vernal. O diagnóstico procura evidenciar o agente etiológico e a confirmação se dá pela realização do teste de provocação conjuntival. O tratamento baseia-se em evitar o contato com os desencadeantes, lubrificação, anti-histamínicos tópicos, estabilizadores de mastócitos, imunossupressores e imunoterapia específica com o objetivo de obter o controle e prevenir as complicações da doença.

Ocular allergy, also known as allergic conjunctivitis, is an immunoglobulin E-mediated hypersensitivity reaction of the eye triggered by airborne allergens, primarily house dust mites and grass pollen. Symptoms usually consist of ocular or periocular itching, watery eyes, and red eyes that may be present year-round or seasonally. Ocular allergy has a high frequency, is underdiagnosed, and can be debilitating for the patient. It is potentially harmful to vision in cases of severe corneal scarring, and in most patients, it is associated with other allergic conditions, especially rhinitis, asthma, and atopic dermatitis. It is classified as perennial allergic conjunctivitis, seasonal allergic conjunctivitis, atopic keratoconjunctivitis, and vernal keratoconjunctivitis. Diagnosis seeks to identify the etiologic agent, and confirmation is given by conjunctival provocation testing. Treatment is based on avoiding contact with triggers, lubrication, topical antihistamines, mast cell stabilizers, immunosuppressants, and specific immunotherapy with the aim of achieving control and preventing disease complications.

Humans , Therapeutics , Conjunctivitis, Allergic , Diagnosis , Keratoconjunctivitis , Patients , Plants, Medicinal , Pruritus , Psychotherapy , Asthma , Signs and Symptoms , Societies, Medical , Vision, Ocular , Climate Change , Conjunctivitis, Allergic/complications , Conjunctivitis, Allergic/epidemiology , Complementary Therapies , Immunoglobulin E , Serologic Tests , Skin Tests , Allergens , Rhinitis , Rhinitis, Allergic, Seasonal , Probiotics , Acupuncture , Pyroglyphidae , Dermatitis, Atopic , Environmental Pollution , Allergy and Immunology , Antibodies, Monoclonal, Humanized , Omalizumab , Mast Cell Stabilizers , Histamine Antagonists , Hypersensitivity , Immunosuppressive Agents , Immunotherapy , Medicine, Ayurvedic , Mites
Arq. Asma, Alerg. Imunol ; 6(1): 84-90, jan.mar.2022. ilus
Article in English, Portuguese | LILACS | ID: biblio-1400109


O SARS-CoV-2 é causador da doença infecciosa COVID-19. A infecção estimula o sistema imunológico a produzir citocinas próinflamatórias. A principal citocina envolvida é a IL-6, e está ligada à gravidade da doença. Devido à associação dos altos níveis de IL-6 com a mortalidade na COVID-19, investiga-se sobre o uso de tocilizumabe (TCZ), um anticorpo monoclonal humanizado antirreceptor de IL-6 humana. O objetivo desta revisão sistemática é avaliar a eficácia do uso do TCZ em pacientes com COVID-19 grave. As buscas foram feitas através das bases de dados Science Direct e PubMed em setembro de 2021. Foram incluídos os ensaios clínicos randomizados com pacientes em um único estágio de COVID-19, casos graves e sem restrição de idade, os quais receberam o TCZ como medicação de intervenção combinado a tratamentos protocolados por cada hospital e associado a corticosteroides. A análise desses estudos demonstrou resultados significantes sobre o uso de TCZ em casos severos de COVID-19. O uso de TCZ associado a glicocorticoides levou a uma redução no índice de mortalidade e de submissão a ventilações mecânicas e a uma melhora expressiva em relação à escala "WHO-endorsed 7-point ordinal scale". Entretanto, não houve melhora relevante quanto ao uso do TCZ de maneira isolada.

SARS-CoV-2 causes the COVID-19 infectious disease that affects the respiratory tract. From the beginning of the infection, the immune system starts to produce pro-inflammatory cytokines and chemokines. The main cytokine involved is IL-6 and is linked to the severity and prognosis of the disease, as it provokes a storm of cytokines and severe inflammatory responses. Due to the association of high levels of IL-6 with severity and mortality in COVID-19, the use of Tocilizumab (TCZ), a humanized anti-human IL-6 receptor monoclonal antibody, which binds to IL receptors, is being investigated. -6 and blocks intracellular signaling reducing cytokine storm and hyperinflammatory state. The aim of this review is to assess the effectiveness of using TCZ in the treatment of patients with severe COVID-19. Searches were performed using the Science Direct and PubMed databases in May 2021. Randomized clinical trials with patients in a single stage of COVID­19, severe cases and without age restriction, who received TCZ as medication for treatment, were included. Intervention was combined with treatments protocoled by each hospital and associated with corticosteroids. The analysis of these studies showed significant results regarding the use of TCZ in severe cases of COVID-19. The use of TCZ associated with glucocorticoids led to a reduction in the rate of mortality and compliance with mechanical ventilation and a significant improvement in relation to the "WHO-endorsed 7-point ordinal scale". However, there was no evidence of relevant improvement when using TCZ alone.

Humans , Antibodies, Monoclonal, Humanized , SARS-CoV-2 , COVID-19 , Patients , Respiration, Artificial , Therapeutics , Cytokines , Interleukin-6 , Adrenal Cortex Hormones , Receptors, Interleukin-6 , PubMed , Cytokine Release Syndrome , Immune System
Arq. Asma, Alerg. Imunol ; 6(1): 127-133, jan.mar.2022. ilus
Article in English, Portuguese | LILACS | ID: biblio-1400122


A doença de Castleman é um distúrbio linfoproliferativo raro, podendo se manifestar sob a forma de massas localizadas ou como doença multicêntrica. A doença de Castleman multicêntrica é caracterizada por adenopatias generalizadas, visceromegalias, manifestações autoimunes e infecções recorrentes. Este artigo apresenta o relato de caso de anemia hemolítica autoimune por anticorpos quentes em paciente com doença de Castleman multicêntrica. Resposta eficaz foi obtida com uso de corticoterapia sistêmica e tocilizumabe.

Castleman disease is a rare lymphoproliferative disorder that can manifest as localized masses or as multicentric disease. Multicentric Castleman disease is characterized by generalized adenopathies, visceromegaly, autoimmune manifestations, and recurrent infections. This article presents the case report of a patient with multicentric Castleman's disease and autoimmune hemolytic anemia by warm antibodies. Effective response was obtained with systemic corticotherapy and tocilizumab.

Humans , Male , Adult , Castleman Disease , Anemia, Hemolytic, Autoimmune , Patients , Adrenal Cortex Hormones/therapeutic use , Antibodies, Monoclonal, Humanized , Lymphoproliferative Disorders , Antibodies
Einstein (Säo Paulo) ; 20: eRC6367, 2022. tab, graf
Article in English | LILACS | ID: biblio-1364787


ABSTRACT Cemiplimab is a novel programmed death-1 inhibitor recently approved for advanced cutaneous squamous cell carcinoma. Immune-related adverse events derived from cemiplimab are similar to other anti-PD-1 drugs, including gastrointestinal and cutaneous toxicities. Oral immune-related adverse events were not reported with cemiplimab in previous studies; thus this case report warns of the fact that the oral cavity may be a site of immune-related adverse events during programmed death-1 block therapy and that this can lead to significant limitations when not properly treated. The present report describes the case of a patient with locally advanced cutaneous squamous cell carcinoma metastatic to cervical lymph nodes who developed dysphagia due to large and painful oral ulcers after a single dose of cemiplimab. The patient also exhibited a sarcoid-like reaction in mediastinal lymph nodes. No immune-related adverse events were found in any other organs. The oral lesions showed significant improvement after topical and short-course systemic corticosteroids, and low-level laser therapy was also performed in the oral lesions. The patient achieved a near-complete response and treatment was discontinued. This article discusses in detail the clinical outcomes and oral toxicity management of cemiplimab therapy for cutaneous squamous cell carcinoma.

Humans , Skin Neoplasms/drug therapy , Carcinoma, Squamous Cell/drug therapy , Oral Ulcer , Antibodies, Monoclonal, Humanized , Lymph Nodes
Arq. Asma, Alerg. Imunol ; 5(4): 385-394, out.dez.2021. ilus
Article in English | LILACS | ID: biblio-1399793


Eosinophilic esophagitis (EoE) is a chronic inflammation in the esophageal mucosa driven by an antigen-mediated abnormal immune response with apparent increasing prevalence worldwide. Genetically predisposed individuals present with a dysfunctional esophageal barrier and an abnormal immune response mediated by Th2 and IgE against certain allergens. Consequently, esophageal lesions can cause dysmotility, fibrosis and loss of esophageal barrier function. Clinical manifestations are age-related and include symptoms of esophageal dysfunction. Diagnosis is established by specific histological features associated with the presence of at least 15 eosinophils per high-power field. Management of EoE includes control of allergic diseases with diet restrictions and/or pharmacological treatment with proton-pump inhibitors and corticosteroids, not completely effective and limited by possible side effects and impairment of quality of life. Although immunological mechanisms of EoE are still less clear than other allergic diseases, biologic trials indicate some promising perspectives for EoE management. The purpose of this review is to present the current evidence of biologic drugs as options for EoE treatment.

Esofagite eosinofílica (EOE) é uma inflamação crônica da mucosa esofágica com resposta imune antígeno-mediada anormal e com aparente aumento mundial na prevalência. Indivíduos geneticamente predispostos se apresentam com quadro de disfunção da barreira esofágica e uma resposta imune, mediada por TH2 e IGE, anormal contra certos alérgenos. Consequentemente, lesões esofágicas podem causar dismotilidade, fibrose e perda da função de barreira. O quadro clínico apresenta variação conforme idade e inclui sintomas de disfunção esofágica. O diagnóstico é estabelecido por achados histológicos específicos associados à presença de, ao menos, 15 eosinófilos por campo de alta potência. O manejo inclui controle do quadro alérgico com restrição dietética e/ou tratamento medicamentoso com bloqueadores da bomba de prótons e corticosteroides. São tratamentos sem completa efetividade, com efeitos colaterais e prejuízo na qualidade de vida. Ainda que os mecanismos imunológicos da EOE sejam menos claros que as demais doenças alérgicas, novos ensaios com imunobiológicos salientam uma perspectiva promissora de tratamento para a EOE. O objetivo desta revisão é apresentar as atuais evidências de uso de imunobiológicos como uma nova opção de terapêutica para a esofagite eosinofílica.

Humans , Adrenal Cortex Hormones , Diet , Proton Pump Inhibitors , Eosinophilic Esophagitis , Antibodies, Monoclonal, Humanized , Omalizumab , Therapeutics , Biological Products , Fibrosis , Immunoglobulin E , Prevalence , Drug Therapy , Endoscopy , Esophageal Mucosa , Immunity , Inflammation , Antigens
Arq. Asma, Alerg. Imunol ; 5(4): 416-421, out.dez.2021. ilus
Article in English, Portuguese | LILACS | ID: biblio-1399806


A dermatite atópica (DA) é uma doença inflamatória crônica da pele, caracterizada por intenso prurido e eczema recorrente. Acomete principalmente a infância, mas tem se tornado bastante prevalente em adolescentes e até em adultos. Apesar de ser geralmente não fatal, apresenta uma carga psicossocial importante para os pacientes e seus familiares. O tratamento da DA envolve a hidratação cutânea e medicações anti-inflamatórias. Em casos graves, pode haver necessidade de terapia sistêmica com imunossupressores como ciclosporina, metotrexato e azatioprina. Mais recentemente, alguns imunobiológicos estão em desenvolvimento para controle da DA. O dupilumabe é um anticorpo monoclonal com ação dupla anti-IL-4/IL-13, liberado para tratamento de crianças a partir de 6 anos com DA grave e adolescentes/adultos com DA moderada a grave. O objetivo deste artigo foi relatar uma série de casos de pacientes adolescentes e adultos com DA grave e sua resposta ao dupilumabe durante a pandemia do COVID-19. Trata-se de quatro pacientes (três do sexo feminino), com piora significativa da DA durante o ano de 2020. Todos tinham história de DA desde a infância, com exames complementares evidenciando sensibilização IgE-mediada para ácaros. Já haviam sido submetidos a diversos tratamentos tópicos e sistêmicos, inclusive a cursos de corticosteroides orais. Nenhum deles havia recebido imunossupressor sistêmico, porém estavam recusando este tipo de tratamento devido ao medo da pandemia. Todos apresentaram boa resposta ao dupilumabe, evidenciada pela redução do número de lesões cutâneas e prurido, com poucos efeitos colaterais. Dois pacientes apresentaram sintomas sugestivos de COVID-19 durante o tratamento com dupilumabe (um com confirmação por PCR), com boa evolução. Concluindo, os pacientes com DA grave possuem grande impacto na qualidade de vida e, durante a pandemia de COVID-19, muitos apresentaram piora significativa do seu quadro dermatológico. Nesse contexto, o dupilumabe se mostrou uma opção terapêutica eficaz e segura para tratamento destes pacientes.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by intense itching and recurrent eczema. It mainly affects childhood but has become quite prevalent in adolescents and even adults. Despite being generally nonfatal, it has an important psychosocial burden for patients and their families. AD treatment involves skin hydration and antiinflammatory medications. In severe cases, systemic therapy with immunosuppressive agents such as cyclosporine, methotrexate, and azathioprine may be necessary. More recently, some biologicals are being developed to control AD. Dupilumab is a monoclonal antibody with anti-IL-4/IL-13 dual-action, approved for the treatment of children from 6 years of age with severe AD and adolescents/adults with moderate to severe AD. This article aimed to report a case series of adolescent and adult patients with severe AD and their response to dupilumab during the COVID-19 pandemic. These are four patients (three female), with a significant worsening of AD during the year 2020. All had a history of AD since childhood, with complementary exams showing IgE-mediated sensitization to mites. They had already undergone several topical and systemic treatments, including courses on oral corticosteroids. None of them had received systemic immunosuppressive agents, but they were refusing this type of treatment due to fear of the pandemic. All had a good response to dupilumab, evidenced by a reduction in the number of skin lesions and pruritus, with few side effects. Two patients had symptoms suggestive of COVID-19 during treatment with dupilumab (one confirmed by PCR) with a good outcome. In conclusion, patients with severe AD have a great impact on quality of life and, during the COVID-19 pandemic, many had a significant worsening of their dermatological condition. In this context, dupilumab proved to be an effective and safe therapeutic option for the treatment of these patients.

Humans , Adolescent , Young Adult , Dermatitis, Atopic , Antibodies, Monoclonal, Humanized , COVID-19 , Patients , Pruritus , Quality of Life , Asthma , Signs and Symptoms , Azathioprine , Therapeutics , Biological Products , Immunoglobulin E , Interleukin-4 , Interleukin-13 , Rhinitis, Allergic , Mites
Rev. Hosp. Ital. B. Aires (2004) ; 41(4): 171-175, dic. 2021. tab
Article in Spanish | LILACS, UNISALUD, BINACIS | ID: biblio-1366760


Introducción: la amiloidosis AA puede ser una complicación de ciertos trastornos inflamatorios crónicos, aunque entre el 21% y 50% puede ser idiopática. No existe un tratamiento específico. El tocilizumab, dirigido contra el receptor de IL-6 y orientado a disminuir la producción de SAA, podría ser eficaz. Métodos: en este estudio informamos datos de 6 pacientes con amiloidosis AA tratados con tocilizumab monoterapia subcutáneo en el período 2011-2018. Los criterios de valoración principales fueron la mejora clínica y bioquímica de los órganos afectados y los parámetros bioquímicos marcadores de inflamación. Resultados: el riñón estaba afectado en todos los pacientes, manifestándose con caída del filtrado glomerular y síndrome nefrótico. La hemorragia digestiva se presentó en un paciente y otro tenía afectación pulmonar en la biopsia. Luego del posterior al tratamiento, todos mejoraron el hematocrito, la albúmina sérica y el índice de masa corporal. El SAA disminuyó en 5 pacientes. Un paciente mejoró su función renal, mientras 4 se mantuvieron estables. Tres pacientes disminuyeron los valores de proteinuria. Conclusión: el tratamiento con tocilizumab podría ser eficaz en el tratamiento de los pacientes con amiloidosis AA. (AU)

Introduction: AA amyloidosis can be a complication of certain chronic inflammatory disorders, although between 21% and 50% can be idiopathic. There is no specific treatment. Tocilizumab, directed against the IL-6 receptor and aimed at decreasing SAA production, could be effective. Methods: in this study, we report data from 6 patients with AA amyloidosis treated with subcutaneous tocilizumab monotherapy between the period 2011-2018. The main endpoints were the clinical and biochemical improvement of the affected organs and the biochemical parameters markers of inflammation. Results: the kidney was affected in all patients, manifesting with a fall in glomerular filtration rate and nephrotic syndrome. Gastrointestinal bleeding occurred in one patient and another had lung involvement on biopsy. After treatment, all improved hematocrit, serum albumin, and body mass index. SAA decreased in 5 patients. One patient improved his kidney function, while 4 remained stable. Three patients decreased proteinuria values. Conclusion: treatment with tocilizumab could be effective in the treatment of patients with AA amyloidosis. (AU)

Humans , Male , Female , Adult , Middle Aged , Aged , Young Adult , Serum Amyloid A Protein/drug effects , Antibodies, Monoclonal, Humanized/therapeutic use , Amyloidosis/drug therapy , Body Mass Index , Receptors, Interleukin-6/drug effects , Antibodies, Monoclonal, Humanized/administration & dosage , Glomerular Filtration Rate/drug effects , Gastrointestinal Hemorrhage/complications , Amyloidosis/blood , Inflammation/complications , Lung Diseases/complications , Nephrotic Syndrome/complications