Impact of synthetic and biological immunomodulatory therapy on the duration of 17DD yellow fever vaccine-induced immunity in rheumatoid arthritis.

BACKGROUND: The 17DD-yellow fever (YF) vaccine induces a long-lasting protective immunity, resulting from humoral and cellular immunological memory. The treatment of rheumatoid arthritis (RA) patients with disease-modifying anti-rheumatic drugs (DMARD) may affect pre-existing 17DD-vaccine protective immunity and increase the risk of acquiring YF infection. Our goal was to determine whether DMARD would affect the duration of YF-specific protective immunity in RA patients. METHODS: A total of 122 RA patients, previously immunized with the 17DD-YF vaccine (1-5, 5-9, and ≥ 10 years) and currently under DMARD therapy, were enrolled in the present investigation. Immunomodulatory therapy encompasses the use of conventional synthetic DMARD alone (csDMARD) or combines with biological DMARD (cs+bDMARD). A total of 226 healthy subjects were recruited as a control group (CONT). Neutralizing antibody responses were measured by a plaque-reduction neutralization test (PRNT), and cellular immunity was evaluated by an in vitro 17DD-YF-specific peripheral blood lymphoproliferative assay. RESULTS: The data demonstrated that csDMARD therapy did not affect the duration of protective immunity induced by the 17DD-YF vaccine compared to that of CONT, as both presented a significant time-dependent decline at 10 years after vaccination. Conversely, cs+bDMARD therapy induced a premature depletion in the main determinants of the vaccine protective response, with diminished PRNT seropositivity levels between 5 and 9 years and impaired effector memory in CD8+ T cells as early as 1-5 years after 17DD-YF vaccination. CONCLUSIONS: These findings could support changing the vaccination schedule of this population, with the possibility of a planned booster dose upon the suspension of bDMARD in cases where this is allowed, even before 10 years following 17DD-YF vaccination. The benefit of a planned booster dose should be evaluated in further studies. TRIAL REGISTRATION: RBR-946bv5 . Date of registration: March 05, 2018. Retrospectively registered.

The 17D-204 and 17DD yellow fever vaccines: an overview of major similarities and subtle differences.

INTRODUCTION: The yellow fever vaccine is a live attenuated virus vaccine that is considered one of the most efficient vaccines produced to date. The original 17D strain generated the substrains 17D-204 and 17DD, which are used for the current production of vaccines against yellow fever. The 17D-204 and 17DD substrains present subtle differences in their nucleotide compositions, which can potentially lead to variations in immunogenicity and reactogenicity. We will address the main changes in the immune responses induced by the 17D-204 and 17DD yellow fever vaccines and report similarities and differences between these vaccines in cellular and humoral immunity . This is a relevant issue in view of the re-emergence of yellow fever in Uganda in 2016 and in Brazil in the beginning of 2017. AREAS COVERED: This article will be divided into 8 sections that will analyze the innate immune response, adaptive immune response, humoral response, production of cytokines, immunity in children, immunity in the elderly, gene expression and adverse reactions. EXPERT COMMENTARY: The 17D-204 and 17DD yellow fever vaccines present similar immunogenicity, with strong activation of the cellular and humoral immune responses. Additionally, both vaccines have similar adverse effects, which are mostly mild and thus are considered safe.

The physician, the Emperor and the fibromyalgia: Charles-Édouard Brown-Séquard (1817-1894) and Dom Pedro II (1825-1891) of Brazil.

The physician Charles-Édouard Brown-Séquard was a neurologist of considerable importance. In 1846 his thesis 'Researches and Experiments on the Physiology of the Spinal Cord' brought out knowledge about the sensory pathways which remains until today. The Emperor, Dom Pedro II was the second and last Emperor of Brazil, reigning for 49 years and remembered for defending the nation's integrity, the end of slavery, support for education and culture, diplomacy and relations with international personalities. He married Dona Teresa Cristina of Bourbon-Two Sicilies (1822-1889) by proxy in 1843, the fourth and last Empress consort of Brazil. This paper reports the exchange of letters between these personalities of the XIX century. Although they lived far from each other and worked in areas so different, they discussed the health of the Empress in letters. Dom Pedro II made contact with Brown-Séquard hoping that ' … your knowledge shall help heal my wife of nervous disease … . ' According to Dom Pedro the Empress suffered ' … for a long time with more or less long interruptions of horrible neuralgic pains in the legs, head and the scalp. Two points on the dorsal spine feel the effects more or less with pressure applied … . ' In addition to describing and documenting the exchange of letters, this paper raises the possibility that the Empress suffered from the fibromyalgia syndrome.

Occurrence of Autoimmune Diseases Related to the Vaccine against Yellow Fever.

Yellow fever is an infectious disease, endemic in South America and Africa. This is a potentially serious illness, with lethality between 5 and 40% of cases. The most effective preventive vaccine is constituted by the attenuated virus strain 17D, developed in 1937. It is considered safe and effective, conferring protection in more than 90% in 10 years. Adverse effects are known as mild reactions (allergies, transaminases transient elevation, fever, headache) and severe (visceral and neurotropic disease related to vaccine). However, little is known about its potential to induce autoimmune responses. This systematic review aims to identify the occurrence of autoinflammatory diseases related to 17D vaccine administration. Six studies were identified describing 13 possible cases. The diseases were Guillain-Barré syndrome, multiple sclerosis, multiple points evanescent syndrome, acute disseminated encephalomyelitis, autoimmune hepatitis, and Kawasaki disease. The data suggest that 17D vaccination may play a role in the mechanism of loss of self-tolerance.

What a rheumatologist needs to know about yellow fever vaccine.

Patients with rheumatic diseases are more susceptible to infection, due to the underlying disease itself or to its treatment. The rheumatologist should prevent infections in those patients, vaccination being one preventive measure to be adopted. Yellow fever is one of such infectious diseases that can be avoided.The yellow fever vaccine is safe and effective for the general population, but, being an attenuated live virus vaccine, it should be avoided whenever possible in rheumatic patients on immunosuppressive drugs. Considering that yellow fever is endemic in a large area of Brazil, and that vaccination against that disease is indicated for those living in such area or travelling there, rheumatologists need to know that disease, as well as the indications for the yellow fever vaccine and contraindications to it. Our paper was aimed at highlighting the major aspects rheumatologists need to know about the yellow fever vaccine to decide about its indication or contraindication in specific situations.

Frequency of sexual dysfunction in women with rheumatic diseases.

OBJECTIVE: To assess the prevalence of sexual dysfunction in women followed up at the Rheumatology Outpatient Clinic of the Hospital Universitário de Brasília and of the Hospital das Clínicas da Universidade de São Paulo with the following rheumatic diseases: systemic lupus erythematosus; rheumatoid arthritis; systemic sclerosis; antiphospholipid antibody syndrome; and fibromyalgia. METHODS: The Female Sexual Function Index (FSfi), obtained by applying a 19-item questionnaire that assesses six domains (sexual desire, arousal, vaginal lubrication, orgasm, sexual satisfaction and pain), was used. RESULTS: This study assessed 163 patients. The mean age was 40.4 years. The prevalence of sexual dysfunction was 18.4%, but 24.2% of the patients reported no sexual activity over the past 4 weeks. Patients with fibromyalgia and systemic sclerosis had the highest sexual dysfunction index (33%). Excluding patients with no sexual activity, the sexual dysfunction rate reaches 24.2%. CONCLUSION: The prevalence of sexual dysfunction found in this study was lower than that reported in the literature. However, 24.2% of the patients interviewed reported no sexual activity over the past 4 weeks, which might have contributed to the low sexual dysfunction index found.

O que o reumatologista deve saber sobre a vacina contra febre amarela / What a rheumatologist needs to know about yellow fever vaccine

Os pacientes portadores de doenças reumáticas são mais suscetíveis à infecção, quer seja pela própria doença de base ou pelo tratamento empregado. É papel do reumatologista prevenir as infecções nesse grupo de pacientes e, dentre as estratégias empregadas, encontra-se a vacinação. No grupo das doenças infecciosas que podem ser prevenidas está a febre amarela. Sua vacina é segura e eficaz na população em geral, mas, assim como as vacinas contendo organismos vivos atenuados, deve ser evitada sempre que possível em portadores de doenças reumáticas em uso de medicamentos imunossupressores. Sendo a febre amarela endêmica em grande parte do Brasil, e estando a vacinação contra essa doença indicada para a população residente em extensa parte do território nacional (além dos viajantes para essas regiões), torna-se essencial que o reumatologista tenha conhecimento da doença, das indicações e contraindicações da vacina contra a febre amarela. Nosso artigo tem o objetivo de destacar os principais aspectos que o reumatologista precisa conhecer sobre a vacina contra a febre amarela, para decidir por sua indicação ou contraindicação após avaliação do risco-benefício em situações específicas.

Patients with rheumatic diseases are more susceptible to infection, due to the underlying disease itself or to its treatment. The rheumatologist should prevent infections in those patients, vaccination being one preventive measure to be adopted. Yellow fever is one of such infectious diseases that can be avoided.The yellow fever vaccine is safe and effective for the general population, but, being an attenuated live virus vaccine, it should be avoided whenever possible in rheumatic patients on immunosuppressive drugs. Considering that yellow fever is endemic in a large area of Brazil, and that vaccination against that disease is indicated for those living in such area or travelling there, rheumatologists need to know that disease, as well as the indications for the yellow fever vaccine and contraindications to it. Our paper was aimed at highlighting the major aspects rheumatologists need to know about the yellow fever vaccine to decide about its indication or contraindication in specific situations.

Frequência de disfunção sexual em mulheres com doenças reumáticas / Frequency of sexual dysfunction in women with rheumatic diseases

OBJETIVO: Pesquisar a prevalência de disfunção sexual em mulheres com as seguintes doenças reumáticas: lúpus eritematoso sistêmico, artrite reumatoide, esclerose sistêmica, síndrome antifosfolípide e fibromialgia acompanhados no Ambulatório de Reumatologia do Hospital Universitário de Brasília e do Hospital das Clínicas da Universidade de São Paulo. MÉTODOS: Utilizou-se o índice de função sexual feminina (Female Sexual Function Index - FSfi), questionário que contém 19 itens que avaliam 6 domínios: desejo sexual, excitação sexual, lubrificação vaginal, orgasmo, satisfação sexual e dor. RESULTADOS: Foram avaliadas 163 pacientes. A média de idade foi de 40,4 anos. A prevalência de disfunção sexual foi de 18,4%, porém 24,2% das pacientes não apresentaram atividade sexual nas últimas 4 semanas. Entre os subgrupos, as pacientes com fibromialgia e esclerose sistêmica foram as com maior índice de disfunção sexual (33%). Se excluirmos as pacientes sem atividade sexual, a taxa de disfunção sobe para 24,2%. CONCLUSÃO: A prevalência de disfunção sexual encontrada neste estudo foi menor em relação à literatura. Entretanto, 24,2% das pacientes entrevistadas negaram atividade sexual nas últimas 4 semanas, o que pode ter contribuído para o baixo índice de disfunção sexual.

OBJECTIVE: To assess the prevalence of sexual dysfunction in women followed up at the Rheumatology Outpatient Clinic of the Hospital Universitário de Brasília and of the Hospital das Clínicas da Universidade de São Paulo with the following rheumatic diseases: systemic lupus erythematosus; rheumatoid arthritis; systemic sclerosis; antiphospholipid antibody syndrome; and fibromyalgia. METHODS: The Female Sexual Function Index (FSfi), obtained by applying a 19-item questionnaire that assesses six domains (sexual desire, arousal, vaginal lubrication, orgasm, sexual satisfaction and pain), was used. RESULTS: This study assessed 163 patients. The mean age was 40.4 years. The prevalence of sexual dysfunction was 18.4%, but 24.2% of the patients reported no sexual activity over the past 4 weeks. Patients with fibromyalgia and systemic sclerosis had the highest sexual dysfunction index (33%). Excluding patients with no sexual activity, the sexual dysfunction rate reaches 24.2%. CONCLUSION: The prevalence of sexual dysfunction found in this study was lower than that reported in the literature. However, 24.2% of the patients interviewed reported no sexual activity over the past 4 weeks, which might have contributed to the low sexual dysfunction index found.

[Vaccination against yellow fever among patients on immunosuppressors with diagnoses of rheumatic diseases]. / Vacinação contra febre amarela em pacientes com diagnósticos de doenças reumáticas, em uso de imunossupressores.

Yellow fever is endemic in some countries. The anti-yellow fever vaccine is the only effective means of protection but is contraindicated for immunocompromised patients. The aim of this paper was to report on a case series of rheumatological patients who were using immunosuppressors and were vaccinated against this disease. This was a retrospective study by means of a questionnaire applied to these patients, who were vaccinated 60 days before the investigation. Seventy patients of mean age 46 years were evaluated. Most of them were female (90%). There were cases of rheumatoid arthritis (54), systemic lupus erythematosus (11), spondyloarthropathy (5) and systemic sclerosis (2). The therapeutic schemes included methotrexate (42), corticosteroids (22), sulfasalazine (26), leflunomide (18), cyclophosphamide (3) and immunobiological agents (9). Sixteen patients (22.5%) reported some minor adverse effect. Among the eight patients using immunobiological agents, only one presented a mild adverse effect. Among these patients using immunosuppressors, adverse reactions were no more frequent than among immunocompetent individuals. This is the first study on this topic.

Vacinação contra febre amarela em pacientes com diagnósticos de doenças reumáticas, em uso de imunossupressores / Vaccination against yellow fever among patients on immunosuppressors with diagnoses of rheumatic diseases

A febre amarela é endêmica em alguns países. A vacina, único modo eficaz de proteção, é contra-indicada em pacientes imunocomprometidos. Nosso objetivo é relatar uma série de casos de pacientes reumatológicos, usuários de imunossupressores, vacinados contra a doença. Foi feito um estudo retrospectivo, por meio de questionário aplicado em pacientes reumatológicos medicados com imunossupressores, vacinados 60 dias antes da investigação. Foram avaliados 70 pacientes, com idade média de 46 anos, 90 por cento mulheres, portadores de artrite reumatóide (54), lupus eritematoso sistêmico (11), espondiloartropatias (5) e esclerose sistêmica (2). Os esquemas terapêuticos incluíam metotrexato (42), corticoesteróides (22), sulfassalazina (26), leflunomida (18), ciclofosfamida (3) e imunobiológicos (9). Dezesseis (22,5 por cento) pacientes relataram efeitos adversos menores. Dentre os 8 pacientes, em uso de imunobiológicos, apenas um apresentou efeito adverso, leve. Entre pacientes em uso de imunussopressores, reações adversas não foram mais freqüentes do que em imunocompetentes. Este é o primeiro estudo sobre o tema.

Yellow fever is endemic in some countries. The anti-yellow fever vaccine is the only effective means of protection but is contraindicated for immunocompromised patients. The aim of this paper was to report on a case series of rheumatological patients who were using immunosuppressors and were vaccinated against this disease. This was a retrospective study by means of a questionnaire applied to these patients, who were vaccinated 60 days before the investigation. Seventy patients of mean age 46 years were evaluated. Most of them were female (90 percent). There were cases of rheumatoid arthritis (54), systemic lupus erythematosus (11), spondyloarthropathy (5) and systemic sclerosis (2). The therapeutic schemes included methotrexate (42), corticosteroids (22), sulfasalazine (26), leflunomide (18), cyclophosphamide (3) and immunobiological agents (9). Sixteen patients (22.5 percent) reported some minor adverse effect. Among the eight patients using immunobiological agents, only one presented a mild adverse effect. Among these patients using immunosuppressors, adverse reactions were no more frequent than among immunocompetent individuals. This is the first study on this topic.