Advances of using antibody against B cell activating factor for treatment of autoimmune diseases / 生物工程学报

In recent decades, the treatment of autoimmune diseases has moved from the use of hormones and conventional immunosuppressive drugs to biological agents. B cell proliferation and maturation play crucial roles in the development of autoimmune diseases. The tumor necrosis factor superfamily ligand B cell activating factor (BAFF) and its receptor mediate B cell survival through regulating signaling pathways. Therefore, BAFF and its receptors are important therapeutic targets for the treatment of autoimmune diseases. This review describes the mechanism of BAFF and its receptor in the human body system and introduces the latest views on how over-activation of BAFF pathway promotes the development of autoimmune diseases including systemic lupus erythematosus, Sjogren's syndrome, and rheumatoid arthritis. In connection to the treatment of the above three diseases, this review discusses the clinical trials and application status of three BAFF-targeting antibody drugs, including Belimumab, Tabalumab and Atacicept. Finally, this review proposes new strategies that targeting the BAFF pathway to provide a new treatment for autoimmune diseases.

Update on classification, diagnosis, and management of immunoglobulin G4-related disease / 中华医学杂志(英文版)

Immunoglobulin G4-related disease (IgG4-RD) is a newly recognized chronic fibro-inflammatory autoimmune disease, and its recognition has been constantly increasing worldwide over the last few years. A correct and timely recognition, as well as appropriate intervention, is crucial for the treatment of IgG4-RD. For certain subtypes of IgG4-RD, organ-specific criteria are formulated to make the diagnosis more accurate. New biomarkers have emerged in the recent years to aid the disease diagnosis, its prognosis prediction, as well as therapy response monitoring. Although recurrence is very common in IgG4-RD, glucocorticoid is still the first-line treatment for the majority of patients. The factors that affect the likelihood of disease relapse are multifaceted. The selection strategy of various steroid-sparing agents is still being explored. Besides, when patients have special sites involvement leading to severe clinical conditions, surgical operation or interventional therapy should also be considered. An update on classification, diagnosis, and management of IgG4-RD is provided in the current study to fully elucidate the recommended clinical practice of this mysterious disease.

Miopatía necrotizante autoinmune: Presentación de un caso clínico / Autoimmune necrotizing myositis: Presentation of a clinical case

Las miopatías inflamatorias (MI) son un grupo heterogéneo de enfermedades musculares de rara ocurrencia, caracterizadas por inflamación de los distintos componentes del tejido muscular, ya sea de forma aislada o, más comúnmente, en el contexto de una afección sistémica. Las miopatías necrotizantes inmunomediadas (MNIM) constituyen un subtipo de miopatía inflamatoria caracterizada por debilidad muscular proximal, necrosis de miofibrillas con mínimo infiltrado celular inflamatorio en la biopsia muscular e infrecuente compromiso extramuscular asociado1. Si bien existen similitudes clínicas e histopatológicas, el espectro de las miopatías inflamatorias es considerablemente variable. Por este motivo, es fundamental realizar estudios complementarios para la identificación correcta del subtipo de MI a fin de determinar su pronóstico e implementar un adecuado tratamiento. Se presenta el caso de una paciente de 29 años, sin antecedentes personales y heredofamiliares de enfermedad autoinmune ni antecedentes patológicos relevantes, que consulta a la Guardia Médica de nuestra Institución por un cuadro de dolor e impotencia funcional en los cuatro miembros, con debilidad muscular a predominio de cintura escapular y en menor medida pelviana, acompañado de astenia, tendencia al sueño e hiporreactividad.

Inflammatory myopathies (IM) or myositis are a heterogeneous group of muscle diseases of rare occurrence. Such diseases are characterized by inflammation of the different components of muscle tissue, which can occur either in isolation or, more commonly, as part of a systemic disorder. Immune-mediated necrotizing myopathies (IMNM) are a type of autoimmune myopathy characterized by proximal muscle weakness, myofiber necrosis with minimal inflammatory cell infiltrate on muscle biopsy and infrequent extramuscular involvement1. Even though there are clinical and histopathological similarities. The spectrum of inflammatory myopathies is considerably variable. Therefore, the performance of complementary studies is essential for the proper identification of the IM subtype to contribute accurately on treatment so determine the better prognosis. The present article shows the case of a young 29 years old, with no personal and family history background of autoimmune disease and no relevant pathological background. The patient consulted the medical ward of the Institution with pain, functional impairment of upper and lower extremities, muscle weakness mainly located in the pectoral girdle area and, although to a lesser degree, in the pelvic girdle area. It was also associated with asthenia, tendency to drowsiness and hyporeactivity.

Uso clínico do rituximabe em doenças autoimunes / Clinical use of rituximab for autoimmune diseases

Doenças autoimunes são doenças universais, e os diagnósticos e tratamentos primários são habitualmente iniciados por clínicos em enfermarias ou ambulatórios, antes de serem encaminhados a especialistas. Além disso, pacientes em uso de biológicos internados em hospitais gerais têm sido cada vez mais frequentes na prática clínica. Conhecer o perfil de segurança, as indicações e os efeitos colaterais dessas drogas deve ser preocupação dos clínicos. Neste trabalho, foi realizada revisão de literatura sobre terapia biológica com rituximabe no tratamento das principais doenças autoimunes sistêmicas da prática clínica: artrite reumatoide, lúpus eritematoso sistêmico, vasculites relacionadas aos anticorpos anticitoplasma de neutrófilo, púrpura trombocitopênica imune e espondilite anquilosante. (AU)

AutoimmunAutoimmune diseases are universal diseases and primary diagnosis and treatment are typically initiated by internists in wards or outpatient clinics before being referred to specialists. In addition, patients on use of biologicals hospitalized in general hospitals have been increasingly common in clinical practice. Knowing the safety profile, the indications, and the side effects of these drugs should be a concern for the internists as well. In this study, the literature review was performed on biological therapy with Rituximab for treating the main systemic autoimmune diseases of clinical practice: rheumatoid arthritis, systemic lupus erythematosus, anti-neutrophil cytoplasmic antibody-associated vasculitides, immune thrombocytopenic purpura, and ankylosing spondylitis. (AU)

Research progress of effect of Rhei Radix et Rhizoma and its anthraquinone in treatment of autoimmune diseases / 中国中药杂志

Rhei Radix et Rhizoma was first recorded in Shennong Ben Cao Jing, with a wide range of pharmacological activities. Autoimmune disease is a kind of disease that damages the tissue structure and function of immune cells and their components due to the impairment of immune tolerance function, including atherosclerosis, multiple sclerosis, gout, rheumatoid arthritis, autoimmune thyroiditis, ulcerative colitis, type 1 diabetes and IgA nephropathy. In recent years, clinical and experimental studies show that Rhei Radix et Rhizoma has potential therapeutic effects on autoimmune diseases. Under the guidance of the theory of traditional Chinese medicine, this paper reviews therapeutic and intervening effects of Rhei Radix et Rhizoma and its main active ingredient anthraquinone on autoimmune diseases. It also puts forward new study directions in view of the existing problems in studies of rhubarb and its anthraquinone, with the aim to provide reference for clinical treatment and scientific studies of effect of Rhei Radix et Rhizomaon autoimmune diseases.

Meningitis crónica autoinmune secundaria a meningitis aguda por neumococo: caso clínico / Autoimmune chronic meningitis secondary to pneumococcal meningitis: report of one case

Pneumococcal meningitis produces several inflammatory disorders in susceptible subjects. A worsening of meningitis can occur on the fourth day of evolution in relation with the withdrawal of steroids. Other complications include the development of inflammatory signs in the post-acute stage of infection associated with disseminated vasculitis of the cerebral blood vessels and, even later, an autoimmune chronic meningitis. All these inflammatory complications are well controlled with the use of steroids. We report a 53-year-old woman with pneumococcal meningitis that had a good response to treatment with antibiotics and steroids. On the four day, after the steroids were discontinued, she complained of headache, became confused, and had an abnormal cerebrospinal fluid (CSF), report CT angiography showed signs of arteritis. She improved when the steroids were re-started. She was discharged in good condition but after slow tapering of the steroids over a four-month period she had a relapse of all her symptoms and had a gait disturbance. On readmission, she had an inflammatory CSF, there were no signs of infection and the cerebral MRI showed meningeal thickening with ventricular space enlargement. She improved again with steroids and she is now well on high-dose steroids but deteriorates each time the steroids are stopped. She experienced both acute and sub-acute inflammatory responses and finally developed a chronic meningitis responsive, and is dependent on steroids.

Autoimmune progesterone dermatitis: A case report

Abstract Introduction Autoimmune progesterone dermatitis (APD) is a rare autoimmune dermatosis characterized by recurrent cutaneous and mucosal lesions during the luteal phase of the menstrual cycle that disappear some days after the menses. Case Report A 34-year-old primipara woman with no significant past medical history and no prior exogenous hormone use, who presented with cyclic skin eruptions starting 1 year after the delivery. The lesions occurred 6 days before the menses and disappeared in between 1 and 2 days after the menstruation ceased. The patient was diagnosed after a positive response to an intradermal test with progesterone and was successfully treated with combined oral contraceptives. The skin eruptions have not returned since the initiation of this therapy. Conclusion Dermatologists, gynecologists, and obstetricians should be aware of this rare entity. Furthermore, if this condition is suspected, a thorough history taking on the menstrual cycle and results of the intradermal progesterone test are mandatory.

Terapia biológica na doença de Crohn: quando iniciar? / Biologic therapy for Crohn's disease: when to initiate?

A doença de Crohn se caracteriza como uma doença inflamatória, que acomete qualquer porção do trato gastrintestinal, resultante da desrregulação imunológica, gerenciada por fatores endógenos e exógenos. As formas de abordagem terapêutica da doença variam conforme sua apresentação clínica e gravidade, bem como o impacto na qualidade de vida do portador. A terapia biológica vem se tornando uma das principais classes utilizadas no contexto desta enfermidade, mas não está claro quando deve ser iniciada ou em que momento a própria doença deve ser considerada moderada ou grave. Sua forma de apresentação multiforme dificulta a classificação dos pacientes nestes grupos. Neste trabalho, foi realizada revisão de literatura sobre a introdução de terapia biológica como tratamento da doença inflamatória intestinal em curso. (AU)

Crohn's Disease (CD) is an inflammatory disease that can affect any portion of the gastrointestinal tract, caused by immune dysregulation, managed by endogenous and exogenous factors. The forms of therapeutic approach of the disease vary significantly according to its clinical presentation and severity, as well as to the impact on patient's quality of life. Biologic therapy has become one of the main classes used in the context of this disease; however, when it should be initiated or at what time the disease itself should be considered moderate or severe is not clear. Its multiform presentation makes it difficult to classify patients in these groups. In this work, a literature review was carried out about the introduction of the biologic therapy as a treatment of the ongoing inflammatory bowel disease. (AU)

Guidelines of the Brazilian Society of Rheumatology for the treatment of systemic autoimmune myopathies

Abstract Background: Recommendations of the Myopathy Committee of the Brazilian Society of Rheumatology for the management and therapy of systemic autoimmune myopathies (SAM). Main body: The review of the literature was done in the search for the Medline (PubMed), Embase and Cochrane databases including studies published until June 2018. The Prisma was used for the systematic review and the articles were evaluated according to the levels of Oxford evidence. Ten recommendations were developed addressing the management and therapy of systemic autoimmune myopathies. Conclusions: Robust data to guide the therapeutic process are scarce. Although not proven effective in controlled clinical trials, glucocorticoid represents first-line drugs in the treatment of SAM. Intravenous immunoglobulin is considered in induction for refractory cases of SAM or when immunosuppressive drugs are contra-indicated. Consideration should be given to the early introduction of immunosuppressive drugs. There is no specific period determined for the suspension of glucocorticoid and immunosuppressive drugs when individually evaluating patients with SAM. A key component for treatment in an early rehabilitation program is the inclusion of strengthbuilding and aerobic exercises, in addition to a rigorous evaluation of these activities for remission of disease and the education of the patient and his/her caregivers.

Encefalitis autoinmunes: Un nuevo diagnóstico para una antigua enfermedad / Autoimmune encephalitis. New diagnosis for an old condition

Las encefalitis autoinmunes son un nuevo grupo de enfermedades de gran trascendencia clínica y terapéutica debido a la buena respuesta en gran parte de los casos a la terapia inmunomoduladora indicada, con un gran porcentaje de curación, sin secuelas neurológicas importantes (cognitivo, motor, crisis o movimientos involuntarios). En el año 2007 se demostró la presencia de auto anticuerpos neuronales en la patogenia de este grupo de enfermedades, con síntomas psicóticos y de movimientos involuntarios como indicadores de la enfermedad. La presente revisión enfatiza el salto crucial y el cambio de paradigmas suscitados tras el descubrimiento de estas encefalitis asociadas a anticuerpos.

Autoimmune encephalitis is a new group of diseases of great clinical and therapeutic importance due to the good response in most cases to the immunomodulatory therapy indicated, with a large percentage of healing without significant neurological effects (cognitive, motor, seizures or involuntary movements). Since 2007, the presence of neuronal autoantibodies in the pathogenesis of this group of diseases has been demonstrated, with psychotic symptoms and involuntary movements as clinical markers of the disease. The present review emphasizes the crucial leap and change of paradigms arising after the discovery of these encephalitis associated with antibodies.

Efectividad de Rituximab en el tratamiento de citopenias autoinmunes refractarias en adultos / Effectiveness of Rituximab in the treatment of cytopenias refractory autoimmune in adults

The term autoimmune cytopenias is referred to a heterogeneous group of diseases characterized by a reduced peripheral blood cell counts in one or more cellular series, because an immunological disorder. The first line therapy is steroids, followed by splenectomy or immunesupressant therapy in non-responders. Rituximab is an anti CD20 monoclonal antibody used as a third line in refractory patients or as an alternative to splenectomy. We present a retrospective study of nine patients with autoimmune cytopenias treated in a public hospital setting with rituximab. Five patients with the diagnosis of inmune thrombocytopenic purpura received it, all of them achieved hematological response (4 complete and one partial). The median time to the best response was 6 weeks, staying in this category after 6 months of follow up. Four patients with autoimmune hemolytic anemia received rituximab, three of them achieving partial response and one was lost from follow up. No severe adverse effects related to rituximab were registered.

Oral pemphigus treated with minipulse therapy

Pemphigus is a chronic potentially fatal autoimmune disorder that causes blisters and erosions of the skin and oral mucous membrane. most of the cases present oral manifestations as the first clinical sign along with dermal lesions. only 0.5 to 3.2 of cases are reported each year per 1,000,000 population with oral manifestations without dermal participation, and is at times difficult to diagnose. we report a case of oral pemphigus vulgaris in a 20 year old female patient without dermal manifestations treated with oral mini pulse therapy. pénfigo oral tratado con terapia minipulse. resumen: el pénfigo es un trastorno autoinmune crónico potencialmente fatal que causa ampollas y erosiones de la piel y la membrana mucosa oral. la mayoría de los casos presentan manifestaciones orales como el primer signo clínico junto con lesiones dérmicas. solo se reportan de 0.5 a 3.2 casos cada año por cada 1,000,000 de personas con manifestaciones orales sin afectación de la piel, y algunas veces es difícil de diagnosticar. presentamos un caso de pénfigo vulgar oral en un paciente de 20 años, sin manifestaciones cutáneas tratadas con mini terapia del pulso oral.

Cyclophosphamide administration routine in autoimmune rheumatic diseases: a review / Rotina de administração de ciclofosfamida em doenças autoimunes reumáticas: uma revisão

Abstract Cyclophosphamide is an alkylating agent widely used for the treatment of malignant neoplasia and which can be used in the treatment of multiple rheumatic diseases. Medication administration errors may lead to its reduced efficacy or increased drug toxicity. Many errors occur in the administration of injectable drugs. The present study aimed at structuring a routine for cyclophosphamide use, as well as creating a document with pharmacotherapeutic guidelines for the patient. The routine is schematized in three phases: pre-chemotherapy, administration of cyclophosphamide, and post-chemotherapy, taking into account the drugs to be administered before and after cyclophosphamide in order to prevent adverse effects, including nausea and hemorrhagic cystitis. Adverse reactions can alter laboratory tests; thus, this routine included clinical management for changes in white blood cells, platelets, neutrophils, and sodium, including cyclophosphamide dose adjustment in the case of kidney disease. Cyclophosphamide is responsible for other rare - but serious - side effects, for instance, hepatotoxicity, severe hyponatremia and heart failure. Other adverse reactions include hair loss, amenorrhea and menopause. In this routine, we also entered guidelines to post-chemotherapy patients. The compatibility of injectable drugs with the vehicle used has been described, as well as stability and infusion times. The routine aimed at the rational use of cyclophosphamide, with prevention of adverse events and relapse episodes, factors that may burden the health care system.

Resumo A ciclofosfamida (CFM) é um agente alquilante vastamente usado para o tratamento de neoplasias malignas e pode ser usado no tratamento de diversas doenças reumatológicas. O erro de administração de medicamentos pode levar à diminuição da eficácia ou ao aumento da toxicidade medicamentosa. Diversos erros ocorrem na administração de medicamentos injetáveis. O trabalho objetivou a estruturação de uma rotina do uso de ciclofosfamida, bem como a criação de um documento de orientações farmacoterapêuticas para o paciente. A rotina foi esquematizada em três fases, a pré-quimioterapia (pré-QT), a administração da ciclofosfamida e a pós-quimioterapia (pós-QT), que levaram em consideração os medicamentos que devem ser administrados antes e depois da ciclofosfamida para prevenção aos efeitos adversos, incluindo náusea e cistite hemorrágica. As reações adversas podem alterar os exames laboratoriais e a rotina incluiu manejo clínico para alteração clínica dos leucócitos, das plaquetas, dos neutrófilos e do sódio incluindo o ajuste de dose de ciclofosfamida em caso de insuficiência renal. A ciclofosfamida é responsável por outras reações adversas raras, mas sérias, como hepatotoxicidade, hiponatremia severa e falência cardíaca. Outras reações adversas incluem perda de cabelo, amenorreia e menopausa. A rotina foi composta também por orientações ao paciente pós-QT. A compatibilidade dos medicamentos injetáveis com o veículo foi descrita, bem como o tempo de estabilidade e o tempo de infusão. A rotina visou ao uso racional da ciclofosfamida e prevenir os efeitos adversos e os episódios de recidiva, os quais podem onerar o sistema de saúde.

Biological therapy and development of neoplastic disease in patients with juvenile rheumatic disease: a systematic review / Uso de imunobiológicos e desenvolvimento de doenças neoplásicas em pacientes com doenças reumáticas juvenis: revisão sistemática

Abstract Juvenile rheumatic diseases affect the musculoskeletal system and begin before the age of 18. These conditions have varied, identifiable or unknown etiologies, but those of an autoimmune inflammatory nature have been associated with an increased risk of development of cancer, regardless of treatment. This study aims to assess, through a systematic review of the literature according to Prisma (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) quality criteria, the risk of cancer in patients with juvenile rheumatic disease, and its association with biological agents. The criteria described by the Strengthening the Reporting of Observational Studies in Epidemiology initiative were used in order to assess the methodological quality of those individual items selected in this study. We analyzed nine publications, from a total of 251 papers initially selected. There was an increase in cancer risk in the population with juvenile rheumatic disease versus the general population. Most specified cancers were of a lymphoproliferative nature. Seven studies did not specify the treatment or not defined an association between treatment and cancer risk. Only one study has suggested this association; in it, their authors observed high risk in patients diagnosed in the last 20 years, a period of the advent of new therapies. One study found an increased risk in a population not treated with biological agents, suggesting a disease in its natural course, and not an adverse effect of therapy. Studies have shown an increased risk of malignancy associated with juvenile rheumatic disease, and this may be related to disease activity and not specifically to the treatment with biological agents.

Resumo As doenças reumáticas juvenis afetam o sistema musculoesquelético e se iniciam antes dos 18 anos. Apresentam etiologia variada, identificável ou desconhecida, porém as de natureza inflamatória autoimune têm sido associadas ao maior risco de desenvolvimento de neoplasias, independentemente do tratamento. Este artigo propõe avaliar, por meio de revisão sistemática da literatura de acordo com os critérios de qualidade Prisma (Preferred Reporting Items for Systematic Reviews and Meta- Analyses), o risco de câncer em pacientes com doenças reumáticas juvenis e sua associação com imunobiológicos. Os critérios descritos pela iniciativa Strengthening the Reporting of Observational Studies in Epidemiology foram usados para avaliar a qualidade metodológica individual dos artigos selecionados no presente estudo. Foram analisadas nove publicações, de 251 incialmente selecionadas. Houve aumento no risco de câncer na população com doença reumática juvenil comparada com a população em geral. A maioria dos cânceres especificados foi de natureza linfoproliferativa. Sete estudos não especificaram a terapêutica ou não definiram associação entre ela e o risco de câncer. Apenas um estudo sugeriu essa associação e observou maior risco em pacientes diagnosticados nos últimos 20 anos, período de advento de novas terapias. Um estudo constatou maior risco em uma população não tratada com imunobiológicos, sugeriu tratar-se da evolução natural da doença, e não do efeito adverso da terapêutica. Os estudos demonstram aumento no risco de malignidade associada a doenças reumáticas juvenis que pode estar relacionada à atividade da doença, e não especificamente ao tratamento com imunobiológicos.

Hidroxicloroquina en el tratamiento de las enfermedades autoinmunes sistémicas / Hydroxychloroquine for autoimmune diseases

Hydroxychloroquine (HCQ) is by far the most frequently used antimalarial for the management of Systemic Autoimmune Diseases. It has immunomodulatory, hypolipidemic, hypoglycemic and antithrombotic properties and it diminishes the risk of malignancies. The most important mechanisms to explain the immunomodulatory actions are its ability to reduce inflammatory pathways and Toll-like receptors activation. The safety profile is favorable. In spite of its low frequency, retinal toxicity is potentially severe. In systemic lupus erythematous HCQ therapy reduces activity, the accrual of organ damage, risk of infections and thrombosis and improves the cardiometabolic profile. It contributes to induce lupus nephritis remission, spares steroid use and increases survival rates. In rheumatoid arthritis, it improves cardiometabolic risk and has a favorable effect in joint inflammation. In Sjögren’s syndrome, an increased lacrimal quality as well as an improvement in objective and subjective inflammatory markers has been demonstrated with HCQ. In Antiphospholipid Syndrome, HCQ is effective in primary and secondary thrombosis prevention. The effectiveness of the drug in other systemic autoimmune diseases is less established. HCQ therapy may improve dermatological manifestations in Dermatomyositis and may have a positive effects in the treatment of Sarcoidosis and Still disease.

Vacunas en pacientes con terapia biológica / Vaccines in patients with biological therapy

Los pacientes portadores de enfermedades reumáticas inflamatorias autoinmunes (AIIRD) tienen mayor riesgo de contraer infecciones, secundario al efecto inmunosupresor de la enfermedad y también por el efecto de los inmunomoduladores utilizados en su tratamiento. Muchas veces los anti-TNF se usan en forma concomitante con metotrexato y corticoides, u otros DMARDs, lo que puede aumentar el riesgo de infección. Entre los efectos adversos graves que se han relacionado con los anti-TNF están las infecciones lo que ha hecho plantear la utilidad de las inmunizaciones para disminuir este riesgo asociado a la enfermedad y a la terapia. Se realizó una revisión de la literatura con el objetivo de analizar los factores que deben ser considerados en el momento de indicar vacunas en estos pacientes.

Patients with autoimmune inflammatory rheumatic diseases (AIIRD) are at higher risk for infections secondary to the immunosuppressive effect of the disease and the effect of the immunomodulators used in their treatment. Anti-TNF are often used concomitantly with methotrexate and corticosteroids, or other DMARDs, which may increase the risk of infection. Among the serious adverse effects that have been associated with anti-TNF are infections that has raised the utility of immunizations to reduce this risk associated with disease and therapy.A review of the literature was carried out with the objective of analyzing the factors that should be considered at the time of indicating vaccines in these patients.

Un desafío clínico: diagnóstico diferencial de pancreatitis autoinmune y cáncer de páncreas. El valor del tratamiento esteroidal de prueba / Focal autoimmune pancreatitis versus pancreatic cancer: value of steroid treatment in the diagnosis

Background: The differential diagnosis of pancreatic cancer and focal forms of autoimmune pancreatitis is complicated since serological tests, IgG4 and CA 19-9 have a low sensibility and specificity. CT scan and magnetic resonance imaging provide clear differentiation in the majority, but not in all cases. Endosonography is the most precise diagnostic procedure and allows to obtain samples for cytology or even histological studies. Aim: To report the experience with 18 cases of focal autoimmune pancreatitis and three cases of pancreatic cancer. Material and Methods: Review of medical records of 18 patients with focal autoimmune pancreatitis and 3 cases of pancreatic cancer. Results: The eighteen patients with focal autoimmune pancreatitis were treated with prednisone 0.5 mg/kg/day obtaining a complete clinical and morphological recovery in all. However, 3 had a relapse and one was operated. During follow up, none has developed a pancreatic cancer. The 3 patients with pancreatic cancer did not respond to steroidal treatment. Conclusions: The quick and dramatic response to steroids of autoimmune pancreatitis, may be useful and is recommended for the differential diagnosis with pancreatic cancer.

Reações infusionais imediatas a agentes imunobiológicos endovenosos no tratamento de doenças autoimunes: experiência de 2.126 procedimentos em um centro de infusão não oncológico / Immediate infusional reactions to intravenous immunobiological agents for the treatment of autoimmune diseases: experience of 2126 procedures in a non-oncologic infusion centre

Introdução: Com o crescimento do uso de drogas imunobiológicas (IBD) ampliamos o conhecimento sobre sua eficácia e segurança. Objetivo: Analisar as reações infusionais imediatas (RII) às IBD endovenosas - infliximabe (IFX), rituximabe (RTX), abatacepte (ABT) e tocilizumabe (TCZ) - no tratamento de doenças autoimunes. Método: Avaliamos 2.126 infusões feitas no CID (Centro de Infusão) em 268 pacientes. A droga usada, a indicação clínica, o tempo de infusão e o uso de pré-medicação foram determinados pelo médico prescritor. Foram consideradas RII todas as intercorrências apresentadas durante a infusão e/ou período observacional de 30 minutos. A conduta adotada nas RII seguiu os protocolos do CID. Resultados: Em relação ao tipo de IBD, as infusões foram distribuídas em: IFX (1.584; 74,5%), TCZ (226; 10,63%), RTX (185; 8,7%) e ABT (131; 6,16%). As RII foram descritas em 87 procedimentos (4,09%): 77 no grupo IFX e 10 no grupo RTX. Não foram descritas RII nos grupos de ABT e TCZ. A maioria foi considerada leve (n = 5; 41,17%) ou moderada (n = 50; 58,81%) e não houve reações graves. Das infusões interrompidas, 79 (92,9%) foram reiniciadas e concluídas com êxito. Apenas seis (0,28%) não foram concluídas por causa das RII. Conclusão: Apesar da diferença entre o número de procedimentos por droga, trata-se de uma análise de "vida real", na qual a incidência de RII foi semelhante à descrita na literatura. A baixa incidência de RII corrobora os dados de segurança tanto de forma quantitativa como qualitativa e ressalta a importância do acompanhamento médico especializado durante a infusão. .

Introduction: With the increasing use of immunobiological drugs (IBD), the knowledge about their effectiveness and safety has increased. Objective: To analyze the immediate infusional reactions (IIR) to intravenous IBD: infliximab (IFX), rituximab (RTX), abatacept (ABT) and tocilizumab (TCZ) on the treatment of autoimmune diseases. Method: 2126 infusions performed in the Infusion Centre - CID in 268 patients were analyzed. The used drug, its clinical indication, infusion time, and use of premedication were determined by the prescribing physician. All intercurrences presented during infusion and/or during a thirty minutes observation period were considered as IIR. The approach adopted in IIR followed the protocols of the Infusion Centre - CID. Results: Regarding the type of IBD, the infused drugs given were: IFX (1584, 74.5%), TCZ (226, 10.63%), RTX (185, 8.7%) and ABT (131, 6,16%). IIR were described in 87 procedures (9.4%): 77 - IFX group and 10 - RTX group. IIR were not described in ABT and TCZ groups. Most were considered as mild (n = 5; 41.17%) or moderate (n = 50, 58.81%) reactions; there were no serious reactions. Regarding to discontinue infusions, 79 (92.9%) were resumed and completed successfully. Only six (0.28% of infusions) were not completed because of IIR. Conclusion: Despite the differences between the number of procedures per drug, ours is a "real life" analysis, where the incidence of IIR was similar to that described in the literature. The low incidence of IIR corroborates the safety data, both quantitatively and qualitatively, and underscores the importance of specialized medical support during infusion. .

Pancreatitis autoinmune: sospecha, diagnóstico diferencial y manejo / Autoimmune pancreatitis: suspicion, differential diagnosis and management

Autoimmune pancreatitis was described only in the second half of the last century. Two types of the disease have been identified: Type 1; Lymphoplasmacytic sclerosing pancreatitis (LPSP), and Type 2, idiopathic duct centric pancreatitis (IDCP). Type 1 AIP is characterized by IgG4 positive lymphoplasmacytic infiltration, storiform periductal fibrosis and obstructive venulitis. It is frequently associated with other autoimmune diseases, it forms part of a systemic IgG4 dependent autoimmune disease, with a tendency of recurrence or progressive pancreatic damage in about 30 percent of the cases. In Type 2, histology reveals ductal destruction by granulocytic epithelial lesions. This type is considered as a pancreas-specific disease, the only association observed is with inflammatory bowel disease. After a successful treatment, recurrence of this disease is an exception. The basis of the diagnosis of AIP is serology and imaging methods. Computed Tomography (CT) scan and magnetic resonance have a good sensibility in the differential diagnosis of pancreatic lesions. Endosonography (EUS) with fine-needle aspiration (FNA) would be the best method to exclude pancreatic cancer. However, its limited accessibility in Chile and high costs make its use rather exceptional. The treatment of AIP is steroids, 0.5-1 mg/kg/day Prednisone for a relatively short period, without the need of permanent treatment in most cases. While possibility of recurrence or progressive pancreatic damage exists, the prognosis is generally good.

La pancreatitis autoinmune es una enfermedad descrita en la segunda mitad del siglo pasado. Se diferencian dos tipos, la pancreatitis esclerosante linfoplasmocítica (PELP-Tipo 1) y la pancreatitis idiopática conducto-destructivo (PICD-Tipo 2). El Tipo 1 está caracterizado por infiltración linfoplasmocitaria por células IgG4 positivas, fibrosis periductal y venulitis obstructiva. Se asocia con otras enfermedades autoinmunes, probablemente forma parte de una enfermedad sistémica IgG4 dependiente, clínicamente tiene la tendencia de recaídas o progresión del daño pancreático en 30 por ciento de los casos. En el Tipo 2 se ve la destrucción de conductos por lesiones granulocíticas epiteliales, considerada como enfermedad específica del páncreas, se asocia sólo con enfermedad inflamatoria intestinal. Después de su recuperación, la recaída es una excepción. El diagnóstico de la PAI se basa en métodos serológicos y morfológicos. Tomografía computada y resonancia nuclear magnética son de buen rendimiento en el diagnóstico diferencial de las enfermedades pancreáticas. Endosonografía con biopsia con aguja fina sería el mejor método para descartar cáncer de páncreas; su disponibilidad en Chile es más bien de excepción. El tratamiento es prednisona 0,5- 1,0 mg/kg/día por un período relativamente corto, sin necesidad de tratamiento de mantención en la gran mayoría de los casos. El pronóstico es bueno, aunque existe posibilidad de recaída o progresión hacia la cronicidad.