Infections in the era of immunobiologicals.

Immunobiologicals represent an innovative therapeutic option in dermatology. They are indicated in severe and refractory cases of different diseases when there is contraindication, intolerance, or failure of conventional systemic therapy and in cases with significant impairment of patient quality of life. The main immunobiologicals used in dermatology basically include inhibitors of tumor necrosis factor-alpha (anti-TNF), inhibitors of interleukin-12 and -23 (anti-IL12/23), inhibitors of interleukin-17 and its receptor (anti-IL17), inhibitors of interleukin-23 (anti-IL23), rituximab (anti-CD20 antibody), dupilumab (anti-IL4/IL13) and intravenous immunoglobulin. Their immunomodulatory action may be associated with an increase in the risk of infections in the short and long term, and each case must be assessed individually, according to the risk inherent to the drug, the patient general condition, and the need for precautions. This article will discuss the main risks of infection associated with the use of immunobiologicals, addressing the risk in immunocompetent and immunosuppressed patients, vaccination, fungal infections, tuberculosis, leprosy, and viral hepatitis, and how to manage the patient in the most diverse scenarios.

Development of a multivariate predictive model for dapsone adverse drug events in people with leprosy under standard WHO multidrug therapy.

BACKGROUND: The occurrence of adverse drug events (ADEs) during dapsone (DDS) treatment in patients with leprosy can constitute a significant barrier to the successful completion of the standardized therapeutic regimen for this disease. Well-known DDS-ADEs are hemolytic anemia, methemoglobinemia, hepatotoxicity, agranulocytosis, and hypersensitivity reactions. Identifying risk factors for ADEs before starting World Health Organization recommended standard multidrug therapy (WHO/MDT) can guide therapeutic planning for the patient. The objective of this study was to develop a predictive model for DDS-ADEs in patients with leprosy receiving standard WHO/MDT. METHODOLOGY: This is a case-control study that involved the review of medical records of adult (≥18 years) patients registered at a Leprosy Reference Center in Rio de Janeiro, Brazil. The cohort included individuals that received standard WHO/MDT between January 2000 to December 2021. A prediction nomogram was developed by means of multivariable logistic regression (LR) using variables. The Hosmer-Lemeshow test was used to determine the model fit. Odds ratios (ORs) and their respective 95% confidence intervals (CIs) were estimated. The predictive ability of the LRM was assessed by the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 329 medical records were assessed, comprising 120 cases and 209 controls. Based on the final LRM analysis, female sex (OR = 3.61; 95% CI: 2.03-6.59), multibacillary classification (OR = 2.5; 95% CI: 1.39-4.66), and higher education level (completed primary education) (OR = 1.97; 95% CI: 1.14-3.47) were considered factors to predict ADEs that caused standard WHO/MDT discontinuation. The prediction model developed had an AUC of 0.7208, that is 72% capable of predicting DDS-ADEs. CONCLUSION: We propose a clinical model that could become a helpful tool for physicians in predicting ADEs in DDS-treated leprosy patients.

Epidemiologic study of 107 cases of families with leprosy in Duque de Caxias, Rio de Janeiro, Brazil.

BACKGROUNDS: ultibacillary patients are the major source of infection in leprosy. Nevertheless, the risk is higher in household contacts between multibacillary patients than paucibacillary patients and in the general population. Household contacts are in close genetic relationship with the index case-patient. OBJECTIVE: To evaluate epidemiological data of the following variables: age, gender, education level, genetic proximity, and type of contact with the index case-patient (household or not) in 107 families with leprosy. METHODS: Home visits were conducted to clinically examine family members. The medical charts of index case-patients and co-prevalent cases were reviewed. RESULTS: The controlled analysis of variables such as type of contact and genetic proximity revealed that household contacts and first-degree kinship are independently associated with a higher chance of contracting the disease. CONCLUSION: Household contacts are often genetically closer to the index case-patient. To investigate the independent relevance of these risks in leprosy surveillance contact studies has been a challenge. Our results confirm literature data that show the influence of genetics in the susceptibility to leprosy per se.

Estudo epidemiológico de 107 focos familiares de hanseníase no município de Duque de Caxias - Rio de Janeiro, Brasil / Epidemiologic study of 107 cases of families with leprosy in Duque de Caxias, Rio de Janeiro, Brazil

FUNDAMENTOS - Os pacientes multibacilares (MB) são a principal fonte de infecção na hanseníase e esse risco é maior nos contatos domiciliares dos pacientes MB do que nos contatos dos paucibacilares (PB) e na população em geral. Entretanto, os contatos domiciliares são os mais próximos do caso-índice (CI), em termos genéticos. OBJETIVO: Analisar dados epidemiológicos das variáveis: sexo, idade, anos de estudo, grau de parentesco com o CI e tipo de contato residencial (intradomiciliar ou peridomiciliar) com o CI em 107 famílias de hanseníase. MÉTODOS: Foram realizadas visitas domiciliares para exame clínico dos familiares. Os prontuários dos CIs e de seus coprevalentes (contatos familiares que também tiveram hanseníase) foram revistos. RESULTADOS: A análise controlada das variáveis tipo de contato e grau de parentesco revelou que o contato domiciliar e o parentesco de primeiro grau estão independentemente associados a uma probabilidade maior de adoecer. CONCLUSÃO: Os contatos domiciliares, em geral, são os mais próximos do caso, em termos genéticos, e aferir a magnitude desses riscos separadamente tem sido um desafio nos estudos de vigilância de contatos em hanseníase. Os resultados deste estudo confirmam os dados da literatura, demonstrando a influência genética no desfecho da hanseníase per se.

BACKGROUNDS: ultibacillary patients are the major source of infection in leprosy. Nevertheless, the risk is higher in household contacts between multibacillary patients than paucibacillary patients and in the general population. Household contacts are in close genetic relationship with the index case-patient. OBJECTIVE: To evaluate epidemiological data of the following variables: age, gender, education level, genetic proximity, and type of contact with the index case-patient (household or not) in 107 families with leprosy. METHODS: Home visits were conducted to clinically examine family members. The medical charts of index case-patients and co-prevalent cases were reviewed. RESULTS: The controlled analysis of variables such as type of contact and genetic proximity revealed that household contacts and first-degree kinship are independently associated with a higher chance of contracting the disease. CONCLUSION: Household contacts are often genetically closer to the index case-patient. To investigate the independent relevance of these risks in leprosy surveillance contact studies has been a challenge. Our results confirm literature data that show the influence of genetics in the susceptibility to leprosy per se.

[The impact of leprosy elimination strategy on an endemic municipality in Rio de Janeiro State, Brazil]. / Os indicadores da hanseníase e as estratégias de eliminação da doença, em município endêmico do Estado do Rio de Janeiro, Brasil.

Various strategies for eliminating leprosy as a public health problem have evolved in the last 20 years. In some countries, especially highly endemic ones, the WHO target rate for leprosy elimination fell far short. The current study aimed to analyze the impact of different strategies for reducing leprosy prevalence in Duque de Caxias, a highly endemic municipality in Rio de Janeiro State, Brazil. The study observed the evolution of traditional operational indicators for the disease and their trends in the last 14 years. The indicators were calculated using the National Communicable Diseases Database (SINAN). Strategies that focused on decentralization of patient care and/or localized campaigns were associated with earlier case detection, reduction in prevalence, and shorter patient time in the active registry. An increase in the annual detection rate could be related to the existence of hidden prevalence or individuals with asymptomatic infection. New complementary strategies are needed to eliminate the disease in Duque de Caxias.

Os indicadores da hanseníase e as estratégias de eliminação da doença, em município endêmico do Estado do Rio de Janeiro, Brasil / The impact of leprosy elimination strategy on an endemic municipality in Rio de Janeiro State, Brazil

As estratégias de controle da hanseníase no mundo vêm sofrendo mudanças na última década, com finalidade de alcançar a meta de eliminação da doença recomendada pela Organização Mundial da Saúde. Atualmente, países mais endêmicos ainda encontram dificuldades de atingir essa meta. O objetivo deste estudo foi descrever as estratégias de eliminação realizadas em Duque de Caxias, município do Estado do Rio de Janeiro, Brasil, com alta endemicidade, e analisar os principais indicadores epidemiológicos e operacionais da doença e sua tendência evolutiva nos últimos 14 anos, a partir do banco de dados oficial de notificação: Sistema de Informação de Agravos de Notificação (SINAN). Estratégias como descentralização do atendimento ao paciente e campanhas localizadas foram associadas ao aumento da detecção de casos mais precoces, e à redução da taxa de prevalência e do tempo de permanência dos pacientes no registro ativo. Um incremento na taxa de detecção anual pode estar relacionado à existência de prevalência oculta ou de indivíduos com infecção assintomática. Novas estratégias complementares necessitam ser formuladas para o alcance da eliminação da doença no município.

Various strategies for eliminating leprosy as a public health problem have evolved in the last 20 years. In some countries, especially highly endemic ones, the WHO target rate for leprosy elimination fell far short. The current study aimed to analyze the impact of different strategies for reducing leprosy prevalence in Duque de Caxias, a highly endemic municipality in Rio de Janeiro State, Brazil. The study observed the evolution of traditional operational indicators for the disease and their trends in the last 14 years. The indicators were calculated using the National Communicable Diseases Database (SINAN). Strategies that focused on decentralization of patient care and/or localized campaigns were associated with earlier case detection, reduction in prevalence, and shorter patient time in the active registry. An increase in the annual detection rate could be related to the existence of hidden prevalence or individuals with asymptomatic infection. New complementary strategies are needed to eliminate the disease in Duque de Caxias.

Estudo de 20 focos familiares de hanseníase no município de Duque de Caxias, Rio de Janeiro / Study of 20 families with leprosy cases from Duque de Caxias - Rio de janeiro - Brazil

FUNDAMENTOS: O conhecimento da transmissão da hanseníase ainda apresenta lacunas devido ao longo período de incubação e ao fato de poucas pessoas expostas adoecerem. Além da exposição ao M. leprae, a susceptibilidade genética é um importante fator de risco para o adoecimento. OBJETIVO: Caracterizar a transmissão da hanseníase em focos familiares de área endêmica urbana no segundo distrito de Duque de Caxias, Rio de Janeiro, RJ. MÉTODOS: Estudo de 20 famílias, a partir de 20 casos índices (CI), diagnosticados no segundo distrito de Duque de Caxias que apresentaram mais de um caso de hanseníase (co-prevalência), com intervalo de até 10 anos entre os diagnósticos. Foi realizado inquérito domiciliar com preenchimento de questionário estruturado e exame dermatoneurológico. RESULTADOS: Houve predominância da consangüinidade entre os que adoeceram (69/75). A possibilidade de adoecer entre os consangüíneos foi 2,8 vezes maior do que a verificada entre os não consangüíneos. Apenas três cônjuges foram acometidos entre os seis doentes não consangüíneos contra 14 filhos. Em duas famílias os casos foram restritos a uma única geração, em cinco houve acometimento de três gerações, e em 13, de duas gerações. CONCLUSÃO: Embora existam outros fatores de risco envolvidos na transmissão da doença (ambientais, sociais, epidemiológicos), não abordados neste estudo, a consangüinidade mostra associação estatística positiva e reforça a importância da vigilância do núcleo familiar, intra e extradomiciliar, considerando as diferentes situações de convivência. São apresentados aqui dados preliminares do estudo de 70 famílias. A inclusão de um maior número de famílias e o estudo do polimorfismo genético deverá aproximar os estudiosos da complexidade desse tema.

BACKGROUND: The transmission of leprosy has issues not understood due to the long incubation period and the fact that only a few of the exposed subjects get sick. Besides the exposure to the M. leprae, genetic susceptibility is an important risk fact for the disease. OBJECTIVE: To study the transmission of leprosy in family clusters in an endemic urban area in the second district of Duque de Caxias, Rio de Janeiro, Brazil. METHODS: Twenty families, who presented more than one case of the disease in a period of ten years, were studied, starting from 20 index cases. The patients were visited in their houses, for dermatologic and peripheric nerves examination. RESULTS: There was a predominance of the disease among consanguineous contacts (69/75). The risk of getting leprosy among those who were consanguineous was 2.8 times higher than among those who were not consanguineous. Only 3 partners were sick among the 6 non-consanguineous, although only 14 offsprings were affected. In two families the disease was restricted to one generation, in five the disease was present in three generations and in thirteen there were two generations of persons with leprosy. CONCLUSIONS: Although other risk factors, not focused in this paper, are involved in the transmission of leprosy, consanguinity shows a positive association and confirms the need of the epidemilogic surveillence of the relatives that are close to the leprosy patients. These are preliminary outcomes of a 70 families study. The inclusion of more families and the study of the genetic polymorphism will provide a better approach in this complex issue.

Hanseníase virchowiana diagnosticada através de exame histopatológico de lesão oral em paciente com pênfigo foliáceo / Lepromatous leprosy diagnosed through the pathological examination of oral lesions, in a patient having pemphigus foliaceus

Os autores apresentam caso de pênfigo foliáceo de longa data, em tratamento com prednisona, que evoluiu com lesão no palato, diagnosticada histopatologicamente como hanseniase virchowiana. Não havia lesões de pele sugestivas de hanseníase. O histopatológico de lesão vesiculosa no abdômen demonstrou a concomitância das doenças. São comentadas as localizações como comuns de manifestação oral de hanseníase