RESUMO

Although the terms "rare diseases" (RD) and "orphan diseases" (OD) are often used interchangeably, specific nuances in definitions should be noted to avoid misconception. RD are characterized by a low prevalence within the population, whereas OD are those inadequately recognized or even neglected by the medical community and drug companies. Despite their rarity, as our ability on discovering novel clinical phenotypes and improving diagnostic tools expand, RD will continue posing a real challenge for rheumatologists. Over the last decade, there has been a growing interest on elucidating mechanisms of rare autoimmune and autoinflammatory rheumatic diseases, allowing a better understanding of the role played by immune dysregulation on granulomatous, histiocytic, and hypereosinophilic disorders, just to name a few. This initiative enabled the rise of innovative targeted therapies for rheumatic RD. In this review, we explore the state-of-the art of rare RD and the critical role played by rheumatologists in healthcare. We also describe the challenges rheumatologists may face in the coming decades.

Assuntos

Doenças Raras , Doenças Reumáticas , Humanos , Doenças Raras/diagnóstico , Doenças Reumáticas/tratamento farmacológico , Reumatologistas , Reumatologia

RESUMO

Amyloidosis is a localized or systemic disease caused by deposition of proteins in the extracellular space of various organs and tissues. As part of the disease, proteins that were originally soluble misfold and acquire a fibrillar conformation that renders them insoluble and resistant to proteolysis. Systemic amyloidosis is a rare, often underdiagnosed condition. In recent years, the incidence of newly diagnosed cases of amyloidosis has been increasing in association with the aging of the population and greater access to diagnostic tests. From a clinical perspective, systemic amyloidosis is frequently associated with involvement of the kidneys (causing nephrotic syndrome), heart (cardiac failure and arrhythmia), and peripheral nervous system (sensorimotor polyneuropathy and autonomic dysfunction). This condition is important to the rheumatologist for several reasons, such as its systemic involvement that mimics autoimmune rheumatic diseases, its musculoskeletal manifestations, which when recognized can allow the diagnosis of amyloidosis, and also because reactive or secondary AA amyloidosis is a complication of rheumatic inflammatory diseases. The treatment of amyloidosis depends on the type of amyloid protein involved. Early recognition of this rare disease is fundamental for improved clinical outcomes.

Assuntos

Amiloidose , Doenças Reumáticas , Humanos , Amiloidose/diagnóstico , Amiloidose/complicações , Doenças Reumáticas/complicações , Síndrome Nefrótica/etiologia , Reumatologistas , Diagnóstico Diferencial , Proteína Amiloide A Sérica

RESUMO

Advances in DNA sequencing technologies, especially next-generation sequencing (NGS), which is the basis for whole-exome sequencing (WES) and whole-genome sequencing (WGS), have profoundly transformed immune-mediated rheumatic disease diagnosis. Recently, substantial cost reductions have facilitated access to these diagnostic tools, expanded the capacity of molecular diagnostics and enabled the pursuit of precision medicine in rheumatology. Understanding the fundamental principles of genetics and diversity in genetic variant classification is a crucial milestone in rheumatology. However, despite the growing availability of DNA sequencing platforms, a significant number of autoinflammatory diseases (AIDs), neuromuscular disorders, hereditary collagen diseases, and monogenic bone diseases remain unsolved, and variants of uncertain significance (VUS) pose a formidable challenge to addressing these unmet needs in the coming decades. This article aims to provide an overview of the clinical indications and interpretation of comprehensive genetic testing in the medical field, addressing the related complexities and implications.

Assuntos

Testes Genéticos , Doenças Reumáticas , Humanos , Testes Genéticos/métodos , Doenças Reumáticas/genética , Doenças Reumáticas/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala , Reumatologia , Sequenciamento do Exoma , Doenças Neuromusculares/genética , Doenças Neuromusculares/diagnóstico , Doenças Hereditárias Autoinflamatórias/genética , Doenças Hereditárias Autoinflamatórias/diagnóstico , Reumatologistas

RESUMO

Autoinflammatory disorders encompass a wide range of conditions with systemic and neurological symptoms, which can be acquired or inherited. These diseases are characterized by an abnormal response of the innate immune system, leading to an excessive inflammatory reaction. On the other hand, autoimmune diseases result from dysregulation of the adaptive immune response. Disease flares are characterized by systemic inflammation affecting the skin, muscles, joints, serosa, and eyes, accompanied by unexplained fever and elevated acute phase reactants. Autoinflammatory syndromes can present with various neurological manifestations, such as aseptic meningitis, meningoencephalitis, sensorineural hearing loss, and others. Early recognition of these manifestations by general neurologists can have a significant impact on the prognosis of patients. Timely and targeted therapy can prevent long-term disability by reducing chronic inflammation. This review provides an overview of recently reported neuroinflammatory phenotypes, with a specific focus on genetic factors, clinical manifestations, and treatment options. General neurologists should have a good understanding of these important diseases.