Littman Jake, Pietro John, Olansen Jon, Phornphutkul Chanika, Aaron Roy K
Department of Orthopedic Surgery, Warren Alpert Medical School of Brown University, Providence, RI 02903, USA.
School of Medicine, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Biomedicines. 2023 Sep 25;11(10):2625. doi: 10.3390/biomedicines11102625.
Endogenous ochronosis, also known as alkaptonuria, is a rare disease known for its bluish-black discoloration of the skin, sclerae, and pinnae, as well as urine that turns black upon standing. Though rarely fatal, joint degradation is a common sequela, and many patients require multiple large joint arthroplasties throughout their lifetime. Though many aspects of the pathophysiological mechanisms of the disease have been described, questions remain, such as how the initiation of ochronotic pigmentation is prompted and the specific circumstances that make some tissues more resistant to pigmentation-related damage than others. In this report, we present the case of an 83-year-old female previously diagnosed with alkaptonuria including high-quality arthroscopic images displaying the fraying of articular cartilage. We also offer a summary of the latest literature on the pathophysiological mechanisms of the disease, including cellular-level changes observed in ochronotic chondrocytes, biochemical and mechanical alterations to the cartilaginous extracellular matrix, and patterns of pigmentation and joint degradation observed in humans and mice models. With these, we present an overview of the mechanisms of ochronotic chondropathy and joint degradation as the processes are currently understood. While alkaptonuria itself is rare, it has been termed a "fundamental disease," implying that its study and greater understanding have the potential to lead to insights in skeletal biology in general, as well as more common pathologies such as osteoarthritis and their potential treatment mechanisms.
内源性褐黄病，又称尿黑酸症，是一种罕见疾病，其特征为皮肤、巩膜和耳廓出现蓝黑色色素沉着，以及尿液静置后变黑。尽管很少致命，但关节退变是常见的后遗症，许多患者一生中需要多次进行大关节置换术。尽管该疾病的病理生理机制的许多方面已被描述，但仍存在一些问题，例如褐黄色素沉着是如何引发的，以及某些组织比其他组织更能抵抗色素沉着相关损伤的具体情况。在本报告中，我们介绍了一名83岁女性的病例，该女性先前被诊断为尿黑酸症，包括高质量的关节镜图像，显示了关节软骨的磨损。我们还总结了关于该疾病病理生理机制的最新文献，包括在褐黄病软骨细胞中观察到的细胞水平变化、软骨细胞外基质的生化和力学改变，以及在人类和小鼠模型中观察到的色素沉着和关节退变模式。通过这些，我们概述了目前所理解的褐黄病软骨病和关节退变的机制。虽然尿黑酸症本身罕见，但它被称为“基础疾病”，这意味着对其研究和更深入的了解有可能为一般骨骼生物学以及骨关节炎等更常见疾病及其潜在治疗机制带来见解。
