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A Avaliação de Tecnologias em Saúde (ATS) considera os domínios de benefícios clínicos, perfil epidemiológico, inovação, custo-efetividade, ética e de equidade no processo de decisão dos gestores em saúde. No contexto dos medicamentos para doenças raras, é desafiador o trabalho da ATS, dada a baixa disponibilidade de evidências robustas e o alto custo unitário das tecnologias. O objetivo da revisão foi analisar as estratégias disponíveis de avaliação das demandas de incorporação de medicamentos para o tratamento de doenças raras em sistemas de saúde. Foi realizada uma revisão rápida com busca estruturada na base de dados MEDLINE (via PubMed), Cochrane Library e Health Systems Evidence. Incluíram-se estudos sobre estratégias de avaliação de medicamentos utilizados para tratamento de doenças raras. Adicionalmente, foram realizadas buscas nas Agências de ATS do Brasil, Austrália, Nova Zelândia, Canadá, Reino Unido, França, Estados Unidos e Alemanha. A síntese dos resultados foi qualitativa com o agrupamento dos achados nos seguintes eixos temáticos: Segurança e efetividade, Custo-efetividade, Impacto orçamentário e Perspectiva da sociedade. Foram identificadas 267 publicações, sendo selecionadas 16 das bases de dados indexadas e 7 da literatura cinzenta. Com a análise dos documentos, pode-se concluir que a adoção de critérios específicos harmonizada com o atual modelo de ATS é um possível caminho a ser seguido no contexto dos medicamentos para doenças raras. Concomitante a isso, abordagens no sentido de incentivo a pesquisa e produção de dados de mundo real e a criação de comitês específicos para tratativa do tema nas agências de ATS apresentam-se como alternativa para lidar com as fragilidades no contexto de doenças raras.
The Health Technology Assessment (HTA) considers evidence regarding clinical benefits, epidemiological profile, innovation, cost-effectiveness, ethics and equity in its assessment process to support managers' decisions. In the context of drugs in rare diseases, the work of the ATS is challenging given the low availability of evidence and the high cost of technologies. The objective of the review was to analyze the available strategies for evaluating the demands for incorporating drugs for the treatment of rare diseases in health systems. A rapid review was performed with a structured search in the MEDLINE database (via PubMed), the Cochrane Library and Health Systems Evidence. Studies on strategies for evaluating drugs used to treat rare diseases were included and, additionally, searches were carried out in ATS Agencies in Brazil, Australia, New Zealand, Canada, United Kingdom, France, United States and Germany. The synthesis of the results was qualitative, grouping the major ones into thematic axes: Safety and effectiveness, Cost-effectiveness, Budgetary impact and Society's perspective. 267 publications were identified, 16 selected from indexed databases and 7 from gray literature. With the analysis of the documents, it can be concluded that the adoption of specific criteria harmonized with the current ATS model is a possible path to be followed in the context of drugs for rare diseases. At the same time, approaches to encourage research and the creation of specific committees to deal with the issue in HTA agencies would complement actions towards the consolidation of this work.
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Orphan Drug Production , Technology Assessment, Biomedical , Rare DiseasesABSTRACT
Introduction: Fanconi Anaemia (FA) is a very rare genetic disease characterised by genetic alterations, which causes con- genital abnormalities in individuals. This clinical case report of Fanconi anaemia, will review classical signs of the disease in detail. The various aspects of this rare condition are examined, with an emphasis on oral manifestations and their impact on af- fected patients overall health. Since this group is more likely to acquire cancers, paediatric dentists must be aware of common oral symptoms and possibly malignant lesions in order to make an early diagnosis and provide thorough care and maintenance of oral health to those who are affected. Case Presentation: A four-year-old female patient was brought by her parents to the Department of Pediatric and Preventive Dentistry, Yenepoya Dental college, with a chief complaint of pain in the upper back tooth region. The child had already been diagnosed with FA. Conclusion: Patients with FA are more prone to get infections, so proper precautions should be taken to avoid any situation that might put them at risk of infection or bleeding. Patients should be motivated to have regular follow-ups and encourage them to maintain good periodontal health, to help prevent the incidence of caries and to monitor their overall oral wellbeing.
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There are more than 7 000 rare diseases and approximately 475 million individuals with rare diseases globally, with children accounting for two-thirds of this population. Due to a relatively small patient population and limited financial resources allocated for drug research and development in pharmaceutical enterprises, there are still no drugs approved for the treatment of several thousands of these rare diseases. At present, there are no drugs for 95% of the patients with rare diseases, and consequently, the therapeutic drugs for rare diseases have been designated as orphan drugs. In order to guide pharmaceutical enterprises to strengthen the research and development of orphan drugs, various nations have enacted the acts for rare disease drugs, promoted and simplified the patent application process for orphan drugs, and provided scientific recommendations and guidance for the research and development of orphan drugs. Since there is a relatively high incidence rate of rare diseases in children, this article reviews the latest research on pharmacotherapy for children with rare diseases.
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Humans , Child , Rare Diseases/drug therapy , Orphan Drug Production , Pharmaceutical PreparationsABSTRACT
Rare diseases in children are characterized by low prevalence, complex pathogenesis, variety, and difficulty in the diagnosis and treatment. With the development of medical services, progress has been made in the diagnosis and treatment of rare diseases. However, due to asymmetric allocation of medical resources at different levels, there are still many shortcomings in the establishment and promotion of the homogenized management system of rare disease diagnosis and treatment. In order to further standardize the homogenized management of rare diseases in children, achieve early and accurate diagnosis and treatment, and improve the quality of life of the children, the Rare Disease Diagnosis and Treatment Center of Tianjin Children's Hospital (Tianjin University Children's Hospital) invited relevant experts in the field to develop recommendations for the management model of homogenized diagnosis and treatment of rare diseases in children from the aspects of information construction, hierarchical diagnosis and treatment, personnel training, scientific popularization, and multi-participation. The recommendations provide reference for the regional homogenization of clinical diagnosis and treatment management system for children with rare diseases.
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Humans , Child , Rare Diseases/therapy , Quality of LifeABSTRACT
Rare diseases refer to a group of single diseases with low incidence rates, complex pathogeneses, severe disease conditions, and rapid progression. Most rare diseases have a genetic background and may occur in childhood. Paying attention to the rare genetic diseases in children and performing early diagnosis and treatment can effectively delay the course of disease and improve the quality of life of children. Many rare diseases can be diagnosed with the help of various experimental techniques, but the diagnosis of rare diseases is still not widely understood. This article summarizes the laboratory diagnostic techniques currently used for rare genetic diseases in children, so as to provide clues for the diagnosis and treatment of such diseases and help to enhance the theoretical understanding and precise medical treatment of rare genetic diseases in children.
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Child , Humans , Rare Diseases/therapy , Quality of LifeABSTRACT
Resumen ANTECEDENTES: Si bien el lupus eritematoso sistémico y la artritis reumatoide son enfermedades suficientemente descritas, no lo es la asociación de estas, que se denomina rhupus, que hace referencia a la manifestación clínica resultante de ambas enfermedades enmascaradas que dificulta el diagnóstico y tratamiento. CASO CLÍNICO: Paciente de 37 años que inició con un cuadro con características de lupus eritematoso sistémico y artritis reumatoide hacía 16 años. Se encontró con alteraciones en los estudios de laboratorio y con hallazgos radiológicos que apoyaron el cuadro de rhupus. Por lo anterior se documenta la evolución de este padecimiento, que coincide con su embarazo y después de éste. CONCLUSIONES: La aparición simultánea de lupus eritematoso sistémico y artritis reumatoide, aun cuando fue reportada desde hace décadas, es una enfermedad rara en frecuencia, por lo que hay escasa información del rhupus solo y más aún en coincidencia con el embarazo.
Abstract BACKGROUND: Although systemic lupus erythematosus and rheumatoid arthritis are sufficiently described diseases, the association of these is not, and is called rhupus, which refers to the clinical manifestation resulting from both diseases masked, making diagnosis and treatment difficult. CLINICAL CASE: 37-year-old patient who started with a clinical picture with features of systemic lupus erythematosus and rheumatoid arthritis 16 years ago. She was found to have alterations in laboratory studies and radiological findings that supported the diagnosis of rheupus. Therefore, the evolution of this condition is documented, which coincides with and after her pregnancy. CONCLUSIONS: The simultaneous occurrence of systemic lupus erythematosus and rheumatoid arthritis, even though it was reported decades ago, is a rare disease in frequency, so there is scarce information on rhupus alone and even more so in coincidence with pregnancy.
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OBJECTIVE To provide reference for the access to medical insurance for rare diseases in China based on the existing access pathway and framework by analyzing the access policy of medical insurance for rare diseases in the United Kingdom （UK）. METHODS After collecting relevant guidelines and policy documents related to drug use for rare diseases in the UK， content analysis method was used to analyze the evaluation mechanism of drug use for rare diseases， reimbursement decision- making standards， stakeholder participation， coping strategies for dealing with uncertainties and risks， and policy implementation effects， and extract the key points of medical insurance access for drug use for rare diseases in the UK， to provide some suggestions for the establishment of medical insurance access system for rare diseases in China. RESULTS & CONCLUSIONS From the perspective of access， the UK had adopted a separate approach and clear criteria to assess and reimburse drugs for rare diseases. From the perspective of evaluation mechanism， multi-stakeholders such as doctors， patients and applicants participated in the decision-making process in the UK. The UK addressed uncertainty and risk by gathering better clinical evidence and using the patient access programme. After the implementation of the policy related to drug use for rare diseases， the UK had achieved remarkable results in terms of funding for drug use for rare diseases， the reimbursement rate of drug application， and the number of funded patients. It is suggested that in the process of establishing and improving the evaluation and reimbursement system for rare diseases drugs in China， the availability of rare diseases drugs should be improved by establishing a separate access assessment path for rare diseases drugs and involving more stakeholders.
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Rare diseases are characterized by extremely low incidence rate and small number of patients in total. The drugs used to treat rare diseases are called orphan drugs. Currently, 450 kinds of rare skin diseases have been identified, most of which lack in effective treatments. Supported by the policy-making from the country and pushed by all sectors of the society, drugs for rare skin diseases have been emerging continuously recently in China. This paper reviews the current accessibility of the orphan drugs for skin rare diseases that have been approved in China and in other countries and regions for a better understanding of rare dermatosis and orphan drugs for the diseases.
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RESUMEN La proteinosis alveolar pulmonar es una entidad clínica caracterizada por la acumula ción de material proteináceo, con alta riqueza en surfactante, mediado por una menor aclaración por parte de los macrófagos alveolares. En pacientes adultos, comúnmente se asocia a fenómenos autoinmunes que tienen como resultado una deficiencia del factor estimulante de colonias de granulocitos y macrófagos, lo que implica alteracio nes en la maduración y disfunción celular, lo que provoca disminución de la degrada ción del surfactante y su acumulación en el espacio alveolar. Su diagnóstico corres ponde a un reto para el clínico, sobre la base de los hallazgos en pruebas de función pulmonar, el patrón en "empedrado" (crazy paving) en la tomografía computarizada de tórax de alta resolución y que se confirma al obtener el material proteináceo en el lava do broncoalveolar. Dada su rareza, el tratamiento ideal permanece por ser elucidado y en la actualidad el pilar del tratamiento es el lavado pulmonar total. Reportamos un caso anecdótico de una paciente de 41 años con proteinosis alveolar pulmonar desde 2011, que ha requerido múltiples lavados pulmonares totales, con pobre respuesta a estos, persistencia de disnea y necesidad de oxígeno suplementario a pesar de realizar el procedimiento, pero con tendencia progresiva a la mejoría en los últimos 2 años. La técnica del lavado no está completamente estandarizada y su uso en Amé rica Latina es aún limitado, por lo que publicamos el protocolo utilizado en el Hospital Santa Clara de Bogotá, Colombia.
ABSTRACT Pulmonary alveolar proteinosis is a clinical entity characterized by the accumulation of proteinaceous material, rich in surfactant, mediated by reduced clearance by alveolar macrophages. In adult patients, it is commonly associated with autoimmune phenom ena resulting in a deficiency of the granulocyte-macrophage colony stimulating factor, which implies alterations in cell maturation and dysfunction, causing a decrease in surfactant degradation and its accumulation in the alveolar space. Its diagnosis poses a challenge to the clinician, based on the findings of pulmonary function tests and the crazy paving pattern of the high-resolution computed tomography of the chest, and is confirmed by obtaining the proteinaceous material in the bronchoalveolar la vage. Given its rarity, the ideal treatment remains to be elucidated, with whole lung lavage currently being the cornerstone of treatment. We report an anecdotal case of a 41-year-old female patient suffering from pulmonary alveolar proteinosis since 2011, who has required multiple whole lung lavages, with poor response to these, with persistent dyspnea and supplemental oxygen requirement even though she has performed the procedure, but with a progressive tendency towards improvement in the last 2 years. The lavage technique is not completely standardized and its use in Latin America is still limited, which is why we publish the protocol used in the Hospital Santa Clara of Bogotá, Colombia.
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Introducción: El tumor neuroectodérmico primitivo periférico de riñón (PNETk) es una enfermedad rara muy agresivo que afecta mayormente a varones jóvenes. Reporte de caso: paciente varón de 19 años con cuadro clínico dolor abdominal, hematuria y masa palpable, en la tomografía se evidencia una enorme tumoración renal izquierda, Se le realiza nefrectomía radical convencional y se envía a estudio patológico más histoquímica resultando de PNETk. Luego paciente siguió su manejo por oncología para quimiterapia inicialmente. Conclusión: El PNETk que describimos representa el primer caso reportado en nuestro país, constituye una entidad clínica única por su rareza siendo un reto hacer diagnóstico y su comportamiento y manejo se sigue basando a reportes de casos debido a su poca frecuencia.
Introduction: Peripheral primitive neuroectodermal tumor of the kidney (PNETk) is a very aggressive rare disease that mainly affects young men. Case report: A 19-year-old male patient with symptoms of abdominal pain, hematuria and a palpable mass, the tomography shows a large left renal tumor. Conventional radical nephrectomy was performed and sent for pathology study plus histochemistry, resulting in PNETk. The patient then continued his oncology management for chemotherapy initially. Conclusion: The PNETk that we describe represents the first case reported in our country, it constitutes a unique clinical entity due to its rarity, being a challenge to make a diagnosis and its behavior and management is still based on case reports due to its infrequency.
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Genomics is an integral part of many pediatric diseases spanning all sub-specialities. While many genetic disorders are diagnosed with the currently available genomic tests, there still are many patients who do not receive a definitive diagnosis. The Indian Undiagnosed Diseases Program is a multicenter effort to address these challenges and unmet needs of rare disease patients where current available genetic tests have failed to make a diagnosis. It embodies the principles of collaborative effort across multispecialty disciplines, and uses detailed phenotype. Diagnostic methods are tailored to patient specifics and the large genomic data is interrogated with precise, in-house bioinformatics pipelines using patient-specific phenotype to build the diagnostic algorithm. The inception of this research initiative in India is a step towards creating awareness and appreciation of the needs for our undiagnosed cohorts to enable appropriate management in this era of precision medicine.
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Epigenetic modification genes are defined as genes whose products modify the epigenome directly through DNA methylation, histone modification or chromatin remodeling.More and more studies have shown that mutations in epigenetic modification genes are an important etiology of rare diseases with abnormal cardiac development.And these diseases usually affect multiple organs including heart due to the change of epigenetic components.Moreover, children′s lives and health are often threatened by a lack of effective drugs and complex cardiovascular malformations.This article reviews advances in molecule genetics of Tatton-Brown-Rahman syndrome, Kabuki syndrome, Rubinstein-Taybi syndrome, CHARGE syndrome and Sifrim-Hitz-Weiss syndrome, and mainly elaborates the mechanism of cardiovascular malformations caused by mutations in corresponding epigenetic modification genes, providing more comprehensive reference for clinical diagnosis and management.
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Resumen ANTECEDENTES: La mastitis granulomatosa idiopática es un padecimiento benigno de la glándula mamaria sumamente raro, simulador de cáncer de mama. Las manifestaciones clínicas más significativas son: nódulo palpable, cambios en la coloración de la piel y mastalgia. Para integrar su diagnóstico se requiere el apoyo de estudios auxiliares de imagen, sin que por ello deje de ser imprescindible la toma de biopsia para establecer el diagnóstico definitivo. No existen pautas de tratamiento debidamente establecidas, pero sí de tratamiento farmacológico y quirúrgico, ésta última se reserva para casos de recidivas, que son frecuentes. CASO CLÍNICO: Paciente de 35 años, nuligesta; acudió a consulta debido a la aparición de un tumor palpable en la glándula mamaria derecha, de siete meses de evolución, con cambios en la coloración y retracción del pezón. La mastografía y ecografía catalogaron el tumor en BI-RADS 5. La biopsia con aguja de corte y citología integraron el diagnóstico de mastitis granulomatosa idiopática. Se indicó tratamiento farmacológico y el tumor desapareció espontáneamente. CONCLUSIONES: La mastitis granulomatosa es una enfermedad rara y de diagnóstico complejo. Para cada paciente habrá un protocolo diferente para evitar el sobretratamiento. Su pronóstico es bueno, a pesar de ser un simulador de cáncer de mama. El tratamiento aún es ambiguo, pero en primera instancia se recomiendan los corticosteroides o inmunosupresores y la cirugía se reserva para casos de recidivas.
Abstract BACKGROUND: Idiopathic granulomatous mastitis is an extremely rare benign entity of the mammary gland, simulating breast cancer. The most significant clinical manifestations are: palpable nodule, skin discoloration changes and mastalgia. The diagnosis requires the support of auxiliary imaging studies, although a biopsy is essential to establish the definitive diagnosis. There are no well-established treatment guidelines, but there are guidelines for pharmacological and surgical treatment, the latter is reserved for cases of recurrence, which are frequent. CLINICAL CASE: A 35-year-old nulligesta patient came for consultation due to the appearance of a palpable tumor in the right mammary gland, of 7 months of evolution, with changes in color and nipple retraction. The mastography and ultrasound catalogued the tumor in BI-RADS 5. The biopsy with cutting needle and cytology integrated the diagnosis of idiopathic granulomatous mastitis. Pharmacological treatment was indicated, and the tumor disappeared spontaneously. CONCLUSIONS: Granulomatous mastitis is a rare disease with a complex diagnosis. For each patient there will be a different protocol to avoid overtreatment. Its prognosis is good, despite being a breast cancer simulator. Treatment is still ambiguous but, in the first instance, corticosteroids or immunosuppressants are recommended and surgical treatment is reserved for cases of recurrence.
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ABSTRACT Research on the genetics, epidemiology, and clinical manifestations of Fabry disease (FD) has increased significantly in recent years. However, some relevant clinical questions still need to be answered to develop better approaches to patient management. This review focuses on answering specific questions raised by Brazilian experts based on their experience in diagnosing and managing patients with FD. The questions are as follows: What is the role of globotriaosylsphingosine in diagnosis? How does one proceed with the diagnosis if there is a variant of unknown significance? What are the earliest and most reliable markers of renal, cardiac, and neurological impairment? What is the prevalence of FD in patients with cryptogenic stroke? What is the average delay in diagnosis in patients with FD? Based on these questions, our objective was to highlight epidemiological, diagnostic, and clinical aspects relating to the literature in the FD field.
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Primary hypomagnesemia with secondary hypocalcemia(HSH) is a rare cause of hypoparathyroidism. This article presents a case of a 26-year-old male with recurrent generalized weakness and tetany, and a literature review of diagnosis and treatment of primary HSH. The biochemical tests revealed the patient had severe hypomagnesemia, mild hypocalcemia, hypokalemia, and hypoparathyroidism. Transient receptor potential melastatin-6(TRPM6) gene mutation were detected by gene test, which confirmed the diagnosis of primary HSH. The patient had been treated with long term oral magnesium supplementation, who remained asymptomatic during the follow-up. Primary HSH is a rare autosomal-recessive disorder caused by mutations in the TRPM6 gene which encoding a magnesium permeable channel expressed in the intestine and the kidney. The primary defect is impaired intestinal absorption of magnesium with secondary renal excretion, leading to a series of clinical symptoms. The treatment is mainly through lifelong magnesium supplementation.
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It is noteworthy that only 5% of more than 7000 described rare diseases are treated. In the era of big data, there is ever-increasing data for understanding biomedicine. The need for efficient and rapid data collection, analyses and characterization methods is pressing. Rare diseases can particularly benefit from artificial intelligence (AI) application. AI, with an emphasis on machine learning, creates a path for such efforts and is being applied to diagnosis and treatment. AI has demonstrated its potential to learn and analyze data from different sources with results in prediction。Presently, there are AI-driven technologies applied for rare diseases and this review aims to summarize these advances. Moreover, this review scrutinizes the limitation and identifies the pitfalls of AI applications in the diagnosis and treatment of rare diseases.
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At present, the diagnosis, treatment, and social security of rare diseases have attracts social attention. As an important part of the multi-level health insurance system in China, commercial health insurance plays an increasingly important role in the supplement to basic medical insurance. Moreover, recently, the benefits of new healthcare reform policies have provided much room and great opportunities for the application of commercial health insurance for rare disease.This paper presents current medical insurance for patients with rare diseases and discuss the necessity and feasibility of bringing rare diseases into the coverage of commercial health insurance, and analyzes the current application and the potential problems of rare disease insurance in the commercial health insurance. This article also gives suggestions to the policies to make full use of the positive role of commercial insurance for the completion of multi-level health insurance system for rare disease.
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Rare disease (RD)is the general term for a class of diseases with very low prevalence.Due to the relatively small number of patients with rare diseases, the diagnosis and treatment, drug research and development, medical safeguard, and scientific research of rare diseases are poorly developed, which highlight the difficulty in diagnosis and treatment, lack of availability of treatment drugs, and lower rate of medical safeguard. In 2018, China's First Edition of Rare Diseases Catalogue was published, which for the first time defined the management scope of rare diseases and promoted research development in field of RD.Since the 13th Five-Year Plan, China has launched a series of policies and measures outlining prevention and treatment of rare diseases, drug research and development, registration, accessing healthcare, and scientific research.In order to further improve the diagnosis, treatment, and management of rare diseases, and better safeguard the health rights and interests of patients with RDs, this paper focuses on the policies and exploration and practice related to rare diseases in China in recent years, and makes suggestions for future policy reviews.
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RESUMEN El síndrome de Prader-Willi es una enfermedad genética rara, caracterizada por anomalías del eje hipotálamo-hipofisario, que cursa con hipotonía grave durante el período neonatal y los dos primeros años de vida, con hiperfagia con alto riesgo de desarrollar obesidad mórbida en la infancia y la edad adulta; así como dificultades de aprendizaje y graves problemas de conducta y/o psiquiátricos. Se presenta el caso de una paciente de 17 años de edad, de color de piel blanca. La paciente mostró entre sus principales manifestaciones: desviación de la fisura palpebral y alteraciones del diámetro, manos y pies pequeños, obesidad, hipogenitalismo, diabetes mellitus, disfunción muscular, deficiencia mental, estatura baja, entre otras. Los criterios clínicos y resultados de estudios complementarios fueron compatibles con el diagnóstico de síndrome de Prader-Willi. Se presenta este caso por lo necesario que resulta describir las características clínicas y genéticas de pacientes con síndrome de Prader-Willi debido a que es una enfermedad genética rara con compromiso importante para la vida futura de quienes la padecen.
ABSTRACT Prader-Willi syndrome is a rare genetic disease, characterized by hypothalamic-pituitary anomalies, which presents with severe hypotonia during the neonatal period and the first two years of life, with hyperphagia with a high risk of developing morbid obesity in childhood and adulthood; as well as learning difficulties and serious behavioral and / or psychiatric problems. A 17-years-old patient with white skin color is presented. The main manifestations of the patient showed: deviation of the palpebral fissure and alterations in the diameter, small hands and feet, obesity, hypogenitalism, diabetes mellitus, muscular dysfunction, mental deficiency, short stature, among others. The clinical criteria and results of complementary studies were compatible with the diagnosis of Prader-Willi syndrome. This case is presented because it is necessary to describe the clinical and genetic characteristics of patients with Prader-Willi syndrome, since it is a rare genetic disease with important compromise for the future life of those who suffer from it.